DC Medical Malpractice & Patient Safety Blog

Last year, a group of doctors at New York’s Memorial Sloan-Kettering Cancer Center refused to prescribe Zaltrap, a new colon cancer drug, because it was twice as expensive as another drug and was not demonstrably more effective. The drug’s manufacturer cut the price in half.

A second drug protest last month, according to the New York Times, involved scores of cancer specialists from around the world in a united effort to persuade pharmaceutical companies to reduce prices on cancer drugs whose annual cost can be horrific.

Writing as a group in Blood, the journal of the American Society of Hematology, the doctors and researchers claimed that the prices of drugs used to treat myeloid leukemia, a cancer of the blood, are astronomical and unsustainable.

And immoral? How else would you describe a drug whose cost can exceed $100,000 … for a year?

The writers, said The Times, suggest that charging such exorbitant prices for a medicine necessary to save lives amounts to profiteering; that it’s gouging people who have no alternative.

So many medical professionals from so many countries (15) signifies that doctors, who can be remarkably ignorant of the cost to patients and insurers of some of their treatment, are starting to get it. As The Times reported, “[S]ome of the specialists even include researchers with close ties to the pharmaceutical industry.”

Many cancer drugs are expensive, but as chronic myeloid leukemia specialists, the journal writers were able to speak only to the medicines used in their field. One, called Gleevec, is a big moneymaker for its manufacturer, Novartis—sales in 2012 were $4.7 billion, making it the company’s best-selling drug. According to The Times, a newer Novartis leukemia drug, Tasigna, generated $1 billion.

The company, according to The Times, says few patients pay the full cost of Gleevec and that it’s priced so high because of the considerable expense in developing it, and because price reflects its value to patients.

So, if we’re interpreting the last point properly, the sicker you are, the more desperate you are, the more you should pay to get better?

When it came onto the U.S. market in 2001, Gleevec cost about $30,000 a year, the writers said. Since then, the price has tripled while newer, even more expensive drugs have also entered the market. As The Times noted, Gleevec’s cost recently came under the scrutiny of the Supreme Court in India, which ruled that it could not be patented. That was good news for manufacturers of generic versions, and patients who need them.

The intent of the Blood writers was to raise cost consciousness and initiate a dialog among manufacturers and members of the medical/insurance communities about controlling drug costs. Many of the 120-some writers work with pharmaceutical companies to develop and test new drugs. As we’ve noted many times, these financial relationships often are fraught with conflicts of interest. So it’s refreshing that this group, which supports a successful pharmaceutical industry, also believes that its prices are much higher than they need to be.

“If you are making $3 billion a year on Gleevec, could you get by with $2 billion?” Dr. Brian Druker, who was the primary academic involved in developing the drug, told The Times. “When do you cross the line from essential profits to profiteering?”

One co-author of the Blood article told The Times he knew several researchers who declined to become authors for fear of losing research money from the industry. The lead author agreed that was a risk. “I am sure I am going to be blackballed,” he said. “My research career will be hurt.”

But, he told The Times, it was time to speak out. “Pharmaceutical companies have lost their moral sense. [Prices] are getting to the point where it is becoming unsustainable.”

Representatives of Novartis said that the company provided Gleevec or Tasigna free to 5,000 uninsured or underinsured Americans each year, and that it has provided free drugs to more than 50,000 people in low-income countries.

But the writers said that despite these programs, most of the estimated 1.2 million to 1.5 million people in the world with chronic myeloid leukemia weren’t receiving the drugs. In some developing nations, cancer experts advocate risky bone marrow transplants because that one-time procedure is less expensive than continuing drug therapy.

The article also said the survival rate for U.S. patients appeared to be less than it should be, maybe because patients can’t afford the medicine. The drugs cost twice as much in the U.S. as in many other countries. And even if some patients have low out-of-pocket drug expenses, somebody in the health system has to pay, so the cost is just shifted, not necessarily reduced. And the writers say that some patient subsidy programs are difficult to use.

Raven Riedesel told The Times that she had been denied by various charities because her husband, a pipe fitter, makes too much money. But their insurance would require a $1,200 to $1,600 a month co-payment for Tasigna. She hadn’t yet approached Novartis itself.

“It would take everything that we had left over after buying necessities and paying our bills,” she told The Times. Now she’s in a clinical trial where she gets Tasigna free. It ends in November.

Manufacturing an excellent product and marketing it well should ensure commercial success. A new lawsuit suggests that it wasn't for Big Pharma player Novartis AG—the company was charged last month with fraud, allegedly for paying kickbacks to pharmacies that switched transplant patients from a less expensive generic drug to to its brand name med, Myfortic.

Paying kickbacks, it seems, seems to be part of the Novartis business plan: In the same week, the U.S. intervened in a private suit from 2011 that claims the company allegedly crossing the palms of physicians with the intent of increasing sales two drugs that treat hypertension, Lotrel and Valturna, and its diabetes drug Starlix.

According to the stories on Bloomberg.com, Novartis, was sued in federal court last month for violating the False Claims Act. That’s the same law Lance Armstrong is accused of violating for defrauding the U.S. by using banned substances when he was sponsored by the U.S. Postal Service.

For seven years, the U.S. says, the Myfortic payments were disguised as rebates and discounts to at least 20 pharmacies that switched patients to Myfortic from drugs sold by other companies. The cost to Medicare and Medicaid was tens of millions of dollars in false claims, the complaint says.

The damage isn’t just financial—patient safety is at issue. “Hundreds, possibly thousands, of transplant patients have undergone switches in their medication as a result of recommendations from pharmacies that were based on undisclosed financial, rather than independent clinical, considerations,” according to the complaint.

Myfortic is an immunosuppressant that helps prevent organ rejection for kidney transplant patients. The drug competes with another manufacturer’s drug, CellCept, which has been available as a generic since 2009. In 2011, Bloomberg reports, Medicare reimbursed Myfortic at more than twice what it did for generic CellCept.
In the older lawsuit, Novartis supposedly treated physicians to luxe dinners, fishing trips, outings at Hooters (class acts!) and provided speaker fees to juice sales; that is, they’re accused of buying physician prescribing loyalty. That commitment should be borne only of science and patient communication. The U.S. says Medicare, Medicaid and other federal health-care programs paid millions for these kickback-inspired claims as well.

In the Myfortic complaint, the U.S. called Novartis a “repeat offender. So, are the penalties for this skanky behavior insufficient, or is Big Pharma just too big to notice them? It wasn’t even three years ago, according to Bloomberg, that Novartis agreed to pay $422.5 million to settle charges that it paid kickbacks and illegally promoted drugs for off-label uses (that is, to treat problems for which the FDA had not given approval; doctors are allowed to prescribe drugs for off-label use, but manufacturers are not allowed to market them for such uses).

We’ve examined the idea that for pharmaceutical companies, paying penalties for illegal drug promotion is just a cost of doing business, and that some doctors are expert practitioners of going to the pharma well.

As part of the 2010 deal, Novartis signed a five-year corporate integrity agreement with the U.S. Department of Health and Human Services requiring promotional activity reforms. The document said that Novartis could be excluded from federal health-care programs for a “material breach.”

We’re waiting.

In the space of a week, ProPublica.org, the nonprofit investigative news site, published two stories about how the FDA permitted dozens of medications—including widely distributed ibuprofen—to remain on the market despite “egregious” violations at the research laboratory that was supposed to scientifically confirm their safety and effectiveness.

The first story detailed how, in 2010, FDA agents pounced on the Houston office of Cetero Research, which conducted research for drug companies worldwide. The FDA had been there plenty of times for routine inspections, but that time it was to investigate a former employee's allegation that the company had tampered with records and manipulated test data.

So guilty was Cetero that the testing facility's president actually acknowledged that much of the lab's work was fraudulent. He had eight flatbed carts rolled in with documents representing five years of data from about 1,400 drug trials. The FDA concluded that the lab’s violations were so pervasive that studies conducted there between April 2005 and August 2009 might be worthless.

“The health threat,” said ProPublica, “was potentially serious: About 100 drugs, including sophisticated chemotherapy compounds and addictive prescription painkillers, had been approved for sale in the United States at least in part on the strength of Cetero Houston's tainted tests. The vast majority, 81, were generic versions of brand-name drugs on which Cetero scientists had often run critical tests to determine whether the copies did, in fact, act the same in the body as the originals. For example, one of these generic drugs was ibuprofen, sold as gelatin capsules by one of the nation's largest grocery-store chains for months before the FDA received assurance they were safe.”

The risks to patients, according to academic experts interviewed by ProPublica, are real, especially for drugs such as blood thinners and anti-seizure medications that must be given at very specific doses. And some generic versions of drugs act differently from name-brand products.

While the FDA investigated and ordered re-tests, European regulators pulled seven drugs from the market.

Twice the FDA said it was requiring drug makers to repeat, re-analyze or audit many of Cetero's tests, and to submit their findings to the agency. Both times the agency allowed some companies to ignore the deadlines.

Now, six months after the last of the deadlines expired and almost three years after Cetero's misconduct was discovered, the FDA has received the required submissions for just 53 drugs. Most companies met the deadlines but a few haven’t submitted new studies, and some companies haven’t done so because they pulled their drugs from the market altogether.

The FDA has reviewed only 21 of the 53 submissions, “raising the possibility,” ProPublica says, “that patients are taking medications today that the agency might pull off the market tomorrow.”

In its defense, FDA authorities told ProPublica that it has found no discrepancies between any original drug and its generic copy and no sign that any patients have been harmed. "It is nontrivial to have to redo all this, to withdraw drugs, to alarm the public and the providers for a large range of drugs," Janet Woodcock, director of the FDA's Center for Drug Evaluation and Research, told ProPublica. "There are consequences. To repeat the studies requires human experimentation, and that is not totally without risk."

She called the potential for harm from drugs tested by Cetero "quite low.'' Despite requests, the FDA has not released to the public the 21 completed reviews.

Maybe the potential for harm is low. But there’s a larger issue here, and that’s transparency. "If there are problems with the scientific studies, as there have been in this case, then the FDA's review of those problems needs to be transparent," David Kessler, FDA head from 1990 to 1997, told ProPublica."FDA may be right here, but if it wants public confidence, they should be transparent. Otherwise it's just a black box."

The medical community at large has reason to be wary. Some of Cetero's suspect research was published in peer-reviewed scientific journals. The medical community relies on those resources. One researcher and a journal editor told ProPublica they had no idea the Cetero tests had been called into doubt.

The second story followed up the earlier piece, and confirmed that the FDA wouldn’t disclose the names of any of the approximately 100 drugs affected by the fraud at Cetero, claiming that to do so would divulge confidential commercial information. Apparently, consumer safety just didn’t figure into the decision.

Thanks to ProPublica, six of the drugs have been identified, one of which was approved after the agency had cited Cetero for misconduct. (To see the list and what is known about the drugs, link here.)

That drug is a generic version of Tussionex, a narcotic cough suppressant/anti-allergy medication manufactured by Tris Pharma. Its chemical name is hydrocodone polistirex/chlorpheniraminepolistirex.

Both of the trials that claimed to show that the generic drug was equivalent to Tussionex, said ProPublica, were analyzed in May and June 2009 at Cetero Research. Proving that a generic drug is equivalent to the brand drug is required before the FDA allows it to be marketed.

The FDA’s inspection report that spring cited Cetero’s falsified data as well as other lab violations while the drug tests were being conducted. Yet five months later, in October, the agency approved the drug for sale in the U.S.

The FDA continued to inspect the Houston lab, and July 2011 was when it deemed its misconduct so “egregious” and pervasive that five years’ worth of tests were potentially “unreliable.”

In April last year, the FDA said that studies analyzed at Cetero Houston between March 2008 and August 2009 needn’t be redone. Instead, they would require only a "verification of data integrity by an independent third-party audit."

Tris Pharma submitted the audit later in the year, and the FDA found it “acceptable.”

The FDA has said that its risk assessment found that the chances were low that drugs tested at Cetero Houston were unsafe. And it said that the fact that it hasn’t found problems with drugs tested there “confirmed” that risk assessment. But often, side effects and other problems from new drugs and devices don’t present for a while. For example, metal hip implants can take several years to fail or contaminate their human hosts with tiny bits of metal.

As ProPublica noted, Cetero filed for Chapter 11 bankruptcy last year and emerged with a new name, PRACS Institute. This year, PRACS filed for bankruptcy. It has reported that the Houston lab has closed.

"Houston (and anywhere else there’s a compounding pharmacy) we have a problem." So says FDA Commissioner Dr. Margaret Hamburg, who wrote a blog on FDA Voice expressing concern about the lack of regulatory authority over the facilities that make customized, prescription medicines like the contaminated steroids that killed 53 and sickened 733 people last year. (See our blog post, “Drugs ‘Compounded’ by Pharmacies: A Disaster Waiting to Happen.”)

Despite resistance by compounding pharmacies, according to AboutLawsuits.com, state and federal agencies have been investigating them, and not liking what they see. Such pharmacies are supposed to fill a specific need: making customized drugs to order for local patients when the meds are not available commercially or in the right delivery system. But some, apparently, operate more like, as AboutLawsuits puts it, “stealth drug manufacturers, selling products nationwide in large amounts without any federal oversight.”

The New England Compounding Center (NECC), the outfit that allegedly caused the outbreak last autumn of fungal meningitis, shipped some 17,000 vials of injectable steroids across the country, and even employed sales representatives to promote it. If that’s not Big Pharma behavior, what is?

It’s cold comfort that NECC is facing criminal charges, lawsuits and bankruptcy—what’s needed, says Hamburg, is a bigger hammer of authority.

As reported by Reuters, Hamburg testified before Congress in November that the law was insufficient to enable the FDA to aggressively enforce rules and punish violators, noting that compounding pharmacies mostly are regulated by the states. Republican lawmakers countered that that the agency has authority but fails to use it properly.

Now, it seems, patient safety is the political football in a game between a divided Congress and the FDA. Last week, as reported by ABC News, House Democrats issued a report showing that most states are lax in their oversight of compounding pharmacies, and congressional investigators say state pharmacy boards lack the information and expertise to oversee them.

Of 49 states in the report, only Missouri and Mississippi provided the exact number of compounding pharmacies in their state. They were the only two that require permits or licenses for pharmacies that perform compounding. No state reported having tracked pharmacies that sell compounded drugs across state lines or in large quantities.

Many states, ABC reported, don’t keep inspection records of compounding pharmacies, and 22 don’t keep histories of problems like contamination, cleanliness and drug potency. For some states, record-keeping amounts to a combination of inspection reports, complaints and "staff recollections."

The average pharmacy board has five inspectors to visit all the pharmacies in the state. Only 19 states train inspectors to recognize problems with sterile compounding.

The next day, Republicans issued a report charging that the FDA’s sloth was the problem, not its authority. According to the Associated Press, the GOP said the agency should have closed NECC years earlier, and has always had the authority to do so. And lawmakers on both sides of the aisle called the FDA on carpet for its lack of aggressive action on compounding pharmacies generally.

In her blog, Hamburg said that the FDA has inspected 31 compounding pharmacies considered high risk and found objectionable conditions at 30 of them. Specifically, the FDA was investigating how well the facilities maintained sterile conditions and minimized the risk of contamination. You can read a summary of these inspections here.

In some cases, the feds had to get court warrants because the pharmacies delayed and resisted inspection, and U.S. marshals had to accompany the inspectors. Can you imagine a meat-processing plant engaging in such an act of defiance? An exotic flower importer turning away customs inspectors charged with keeping pests out of the country? And these people claim to be providing products people trust with their lives?

No wonder Hamburg seeks authority and resources for the FDA to police compounding pharmacies nationwide before there are violations, before someone else gets hurt or killed because the people who made their medicine took less care with hygiene than they would changing the fry oil at McDonald’s.

Sometimes, we read an article or book about health, medicine and/or patient safety that’s fascinating but too long to summarize fairly in a blog post. So here’s a shout-out to a few recent stories you might want to look up, on a common theme.

According to the Centers for Disease Control and Prevention (CDC), drug overdose death rates in the U.S. have more than tripled since 1990 and have never been higher. Most of these deaths, says the CDC were caused by prescription drugs. In the last several months, the Los Angeles Times has published a series of investigative articles about the epidemic of prescription deaths. The four-part series explains how legal drugs have deadly outcomes, how reckless doctors and rogue pharmacists contribute to the problem, how regulatory authorities allow problems to fester and what they can do to address it. Link here.

Also, see our blog, “Doctors Don’t Know Dangers of Narcotics, and FDA Leaves Drug Makers in the Driver’s Seat.”

“NPR’s Akathisia Blind Spot,” was posted on Paul John Scott’s website devoted to “groupthink in science medicine and fitness—popular culture and the madness of crowds.” In the eloquent essay, he indicts the media for continuing to ignore a major side effect of a class of anti-depressant drugs known as SSRIs—selective serotonin reuptake inhibitors--including Celaxa and Lexapro. “[T] he problems with SSRIs and suicide seems no closer to being articulated in the culture at large, let alone resolved, beyond a few ardent voices and the small print on some drug labels that, thanks to the silent skepticism of so many, no one really knows what to think of.” Link here.

“Bad Pharma: How Drug Companies Mislead Doctors and Harm Patients,” Dr. Ben Goldacre’s new book, addresses our culture’s willingness to believe that drug treatment is based on evidence, that doctors are familiar with the latest drug studies, that drug research is pure science unpolluted by conflicts of interest and that when it comes to drug safety, regulators have our back.

As readers of this blog know, that’s fiction. Goldacre shows how the manipulation of the prescription drug market has been protected from public scrutiny because it’s too complex to capture in a sound bite. Goldacre untangles the tale in the hope that all patients and medical professionals can understand the tricks and distortions inherent in Big Pharma. Link here.

Patients depend on their doctors not only for diagnosing and treating health problems, but for keeping current with important medical news. So it’s unsettling to learn that many neurologists--doctors who treat the brain and central nervous system—may not be getting important information in timely fashion about the risks of certain anti-epileptic drugs.

According to a preliminary study for the American Academy of Neurology (AAN), FDA drug alerts about anti-epileptic drugs might not be reaching the target neurologist community, and even if they do, some doctors might not be retaining or acting on that safety information.

According to MedPageToday.com, 2 in 10 respondents to an online survey of AAN members who treat epilepsy patients were not aware of major FDA drug safety warnings that were reported by electronic messages.

The valproate drugs, whose brand names include Depacon, Depakote and Stavzor, are prescribed for seizures, bipolar disorder and to prevent migraine headaches. Also, they are used off-label (which means the FDA has not approved them for this specific use) for other psychiatric conditions.

Even if neurologists were aware of the alerts, only about 2 in 10 could remember what, exactly, was the specific risk identified in the alert.

The study can’t be construed to define a whole industry practice—as MedPage Today points out, neurologists who chose to participate in this survey might be more informed than neurologists at large. The survey sampled 505 AAN-affiliated neurologists via email and Internet.

Its subject was four anti-epilepsy drug safety risks recently announced by the FDA. That agency issues medication safety warnings via email and on its website, but only people who have signed up to receive Drug Safety Communications and MedWatch Alert emails get the updates automatically. The FDA also emails health-care professionals via physician specialty organizations, black box warnings or "Dear Healthcare Provider" letters, as well as in published articles on company and third-party websites. (Black box labels are so named for the black border around the text on a package insert, label and other literature warning of a dangerous possible event; it’s the sternest, most serious warning the FDA requires.)

The FDA’s alerts included:

• a gene-screening recommendation for Asian patients before receiving carbamazepine (Tegretol);


• a product warning about suicide in 11 anti-epileptic drugs;


• a recommendation for counseling and a labeling change because of the risk of congenital malformations in pregnant women treated with valproate;


• a communication and labeling change to show a risk of impaired cognitive development in fetuses exposed to valproate.

But “general awareness” isn’t satisfying to patients whose lives might be at risk. About 7 in 10 health-care professionals correctly remembered specific risk details from the carbamazepine communication. Only 6 in 10 did so for the suicide risk of 11 drugs.

Somewhat more than 3 in 10 remembered details of the congenital malformation risk of valproate, and nearly half remembered details of the cognitive development risk of valproate.

Most of the neurologists said they were aware of the requirement for genetic screening, but nearly 8 in 10 reported that they did not perform it.

The study’s authors conclude that there’s a systemic breakdown in delivering vital drug information to neurologists. To say the least…

Whether it’s Fritos, Corvette or iPod, certain products have undeniably wonderful names crafted by deep-thinking marketers. The drug industry is no different in hoping that the names they give their creations will resonate with doctors and, sometimes, consumers.

An interesting story recently published on Reuters.com explained how prescription drugs get their names, and how the sexiest letters in the alphabet often are the key. Big Pharma, it seems, is partial to names beginning with X and Z because they are unusual—that is, they don’t appear in many words—and therefore are memorable. Also, they have the quality of being “fricative,” a wonderful word that means they have a sense of speed or fluidity.

(Why being fast or fluid translates into good, or effective, is something that escapes us. But we’ll just roll with it for now.)

A professor of psychology and linguistics told Reuters that manufacturers who want to appeal to the psyche need memorable, distinctive names not only in terms of sound, but appearance. That’s why drug names like Xtandi (lung cancer), Zytiga (prostate cancer) and Zoloft (anxiety/depression) are hot.

Since 1995, Reuters says, 15 drugs whose names begin with X have been approved by the Food and Drug; seven were launched in the last 2 ½ years.

But most kids can’t be named Rainbow Moonbeam without some social backlash, so names for drugs also must be practical. Both the FDA and regulators in Europe have guidelines for acceptable names for medicine. Manufacturers are not allowed to call their drugs by a name similar in sound or appearance to another drug because somebody might take the wrong medicine by mistake. Also, a pharmacist might mistake a doctor’s handwriting on the prescription and dispense the wrong drug. Drugs with letters including X and Z are less likely to be misinterpreted.

Pronunciation seems to be a decidedly lesser consideration. The novelty of a name is more important than someone’s ability to pronounce it. Call it “the artist formerly known as Prince” phenomenon.

But mostly, patients don't choose these drugs, their doctors do. So manufacturers coin their names for that group, rather than the general consumer. If a consumer product like an eyelash builder is named Latisse because it sounds lush and consumers can ask for it, Reuters says, a cancer drug must appeal to oncologists and its name indicate something about its medical/scientific basis.

For example, a new Pfizer drug, Xeljanz, is approved to treat rheumatoid arthritis. One branding expert told Reuters that it perfectly represents both innovation and ability. "It includes both X and Z ... and the name is really key to the product profile," he said, explaining that the drug works by blocking certain molecules known as Janus kinases.

"For a doctor who is anticipating this product, when they see that JAN that might be the light bulb."

This whole discussion is amusing, but kind of creeps us out. Prescribing or taking a drug because you like its name is like buying a car because you like the color. Except that there’s far more potential for harm.

Or are we just over-thinking this?

As we reported a year ago, the U.S. Supreme Court prohibited injured patients from suing generic drug companies because such companies didn’t control the information on their labels—such information was held to be the exclusive responsibility of the pharmaceutical companies that developed the brand name drug. The court said that if the generic manufacturers are prohibited from printing warnings about drug side effects, patients shouldn’t be able to sue them when bad things happen after taking the drug.

Last week Pop Tort, the civil justice blog from the Center for Justice & Democracy, summarized where we are now in the responsibility game. The site used the example of one woman’s experience with sulindac, the generic version of Clinoril, an anti-inflammatory.

The patient was prescribed Clinoril for shoulder pain, and her pharmacist dispensed sulindac for insurance purposes. It wasn’t long before her skin started burning off. She spent two months in a burn unit in a medically induced coma. She spent a year on a feeding tube and survived only with severe disfigurement and permanent lung, esophagus and vision damage. She couldn’t read, drive, work or eat normally.

She sued for compensation because the drug was “unreasonably dangerous.” In the discovery process, she learned, according to Pop Tort, that there were more adverse event reports made to the FDA over sulindac than any other similar nonsteroidal anti-inflammatory drug; that it was known that sulindac’s rate of life-threatening conditions was comparable to another drug the FDA had recommended be removed from the market, but that this knowledge was not given to the FDA.

The jury in her trial awarded her $21 million.

Sulindac’s manufacturer, Mutual Pharmaceutical, appealed to the U.S. Supreme Court to deny the award and protect it from any harm its drugs cause patients. Mutual, says Pop Tort, has 80% of this market.

Mutual’s argument is based on last year’s case, Pliva v. Mensing, that held that generic drug manufacturers can’t be held responsible for failing to warn patients about a drug’s side effects. By federal law, generic drug manufacturers must use whatever label was approved for the brand-name drug.

“But the issue here is quite different,” says Pop Tort. “There’s no federal law that requires a company to sell a generic drug. The manufacturer could simply decide not to make and sell the drug they know to be unsafe – as they clearly did here (and as the lower court held).”

At least one Congressman, Henry Waxman of California, who has been instrumental in writing laws on generic drugs, supports the plaintiff’s case against Mutual. “[D]amage suits advance public health,” he said. “Product liability lawsuits help to uncover information that can lead to safer products. Material produced in litigation can help the public and the FDA to identify problems with particular drugs and can add to physicians’ and public understanding of the risks of the products and flaws in the regulatory system.”

This is a simple concept. You cannot make informed choices, you cannot weigh risks against benefits, if you lack essential information. Product liability litigation yields information that helps patients and doctors make decisions, and enables drug companies to address product defects. Or it should anyway.

After the Mensing decision last year, Pop Tort notes, U.S. Senate Judiciary Chair Pat Leahy of Vermont introduced the Patient Safety and Generic Labeling Improvement Act to try to correct the injustice. He explained that now, “If a consumer takes the brand-name version of drug, she can sue the manufacturer for inadequate warnings. If the pharmacy happens to give her the generic version, she will not be compensated for her injuries. The result is a two-track system that penalizes consumers of generic drugs – even though many consumers have no control over which drug they take, because state law and their health insurance plan require them to take generics if they are available.”

It’s about accountability. It’s about full disclosure. When you’re afraid of information, it seems to us, you have something to hide.

This week the FDA renewed a warning it had first sounded last year about the antibiotic azithromycin. But it wasn’t just a reminder that the drug, whose brand name is Zithromax, or Zmax, carries risks—this was a graver assessment that azithromycin can cause the heart’s electrical rhythms to change which, for some people, can be fatal.

As widely noted in the media, including the New York Times, the initial warning came on the heels of research published in the New England Journal of Medicine (NEJM) last spring. Since then, warning labels have been included on the drug’s packaging, and the FDA has been reviewing the study.

The data showed a modest increase in the likelihood of death in people with a five-day course of azithromycin compared with patients treated with other antibiotics including amoxicillin (Amoxil) and ciprofloxacin (Cipro, Proquin).

As The Times notes, azithromycin was believed to be safer than a couple of other related antibiotics, erythromycin (Erythromycin) and clarithromycin (Biaxin), which also can raise the risk of death. But it has leapfrogged those drugs in concern over heart problems. The new, more serious FDA warning says patients at risk of the heart arrhythmia include the elderly and those with a history of heart problems, low blood levels of potassium or magnesium, slow heart rates and anyone taking medication that slows the heart rate.

People typically are prescribed azithromycin for bacterial infections such as bronchitis and pneumonia, sore throats and earaches. Commonly called “Z-Pak,” it’s taken for five days, which most people find preferable to many other antibiotics that must be taken for twice as long.

If you are taking azithromycin or if your doctor prescribes it, ask about the cardiac risks of the drug. Ask if any other drugs you take slow your heart rate. Ask if another antibiotic in the same class, such as fluoroquinolones (levofloxacin, moxifloxacin, norfloxacin) can be substituted for azithromycin. Like all drugs, they, too have potential risks and side effects, but do not present the cardiac risks of azithromycin.

Heartburn is one of the most common gastrointestinal disorders and, apparently, a problem that leads too often to overprescribing drugs. That’s the conclusion of a study in the Journal of Internal Medicine by researchers from Northwestern University.

As summarized on AboutLawsuits.com, doctors often write prescriptions for proton pump inhibitors (PPIs) at excessive doses. And they often advise patients to take the medicine for too long. The risks of such overuse are bone fractures, infections and pneumonia.

Such drugs include Nexium, Prilosec, Prevacid and Protonix.

In addition to the generic problem known as “heartburn” or acid reflux (burning in the chest, neck or throat caused by stomach acid moving up into the esophagus), PPIs are prescribed for gastroesophageal reflux disease (GERD), stomach and intestinal ulcers and inflammation of the esophagus. The medicine reduces the amount of acid in the stomach.

The researchers said appropriate prescriptions are the lowest effective dose for four to eight weeks. If the symptoms aren’t relieved by then, doctors are supposed to seek other causes for the problem and investigate different types of treatments. But, too often, that’s not what happens.

Of 1,600 veterans diagnosed with GERD at a Veterans Affairs Hospital, the study showed that about 373 were prescribed high doses from the start and were kept on the pills for 90 days or longer. More than 8 in 10 patients received at least one refill, and many took the drug for more than two years.

As noted on AboutLawsuits, in 2010 and again in 2011 the FDA compelled manufacturers of proton pump inhibitors to update their warning labels to include information about the risks associated with use of the medications. (See our blog, “New Safety Concerns Over Celexa, Proton Pump Inhibitors.”) Nexium is the most popular drug in this class, and generates more than $6 billion in annual sales.

Over-the-counter versions of PPIs do not appear to pose the same risks.

Several former patients who suffered bone fractures, says AboutLawsuits, are suing AstraZeneca, the manufacturer of Nexium, claiming that the company did not sufficiently warn consumers about the risks associated with long term use.

If you have gastrointestinal pain, Choosing Wisely, an initiative of the American Board of Internal Medicine (ABIM) Foundation, recommends that before using a prescription PPI you try other treatments Choosing Wisely says that as many as 7 in 10 people taking a PPI were never diagnosed with GERD, that, instead, they might have less serious heartburn. That often can be eased with dietary and other lifestyle changes and, if necessary, antacids like Rolaids and Tums.

If your doctor prescribes a PPI for acid reflux or any other disorder, ask if the dose is the lowest possible for your symptoms. Don’t take it for longer than six weeks. If your symptoms haven’t resolved, discuss with your doctor if there might be another reason besides the one diagnosed for the symptoms, and whether other treatment options are available. If you take any of these drugs and have an adverse response, file a report with the FDA’s MedWatch program.

Counterfeit drugs are a global problem. There’s no single solution to curbing the availability of falsified, substandard and unregistered drugs, but a report issued earlier this month by the Institute of Medicine (IOM) is a meaningful effort to acknowledge and address the problem. The IOM is an independent, nonprofit organization that provides unbiased and authoritative advice to decision makers and the public.

As reported on FDA Law Blog, the report, “Countering the Problem of Falsified and Substandard Drugs,” discusses, among other issues, the poor quality of drug ingredients and the lack of global regulation.

The report makes 12 recommendations international regulatory authorities should follow to combat the proliferation of this bad medicine throughout the world. Among them are:

• Adopt universal definitions for “substandard,” “falsified ,” and “unregistered” drugs.


• Establish and strengthen governmental systems to identify substandard, falsified and unregistered drugs.


• Create “investment vehicles” for drug manufacturers who are interested in upholding international standards.


• Promote government support in low- and middle-income countries for stronger international manufacturing and quality-control standards.


• Fund public education campaigns on the dangers of falsified and substandard medicines.


• Implement stronger licensing standards for wholesalers and distributors, and establish a public database of licenses to be maintained by FDA.


• Authorize and fund a “mandatory track and trace” system to be implemented by FDA.

Such drugs might be contaminated, like the steroid injections last year that caused an outbreak of meningitis. They might contain the wrong or no active ingredient. They might contain the right active ingredient but at the wrong dose. Some of effects of taking counterfeit drugs are merely irritating, but some are lethal.

As more foreign countries manufacture drugs taken by Americans, we have more exposure to unregulated businesses whose processes and premises don’t meet our standards and are beyond our reach. The global problem is our problem.

As FDA Law Blog interprets the IOM, “falsified” drugs “carry a false representation of identity or source or both”; they’re often substandard, which means they vary from country to country, and can range from a legitimate product in fake packaging, or a fake product in legitimate packaging.

“Substandard” drugs “do not meet the specifications given in the accepted pharmacopeia [that’s like a drug recipe book—pharmaceutical products described by their formulas and methods of preparation] or in the manufacturer’s dossier.” The complication is that what’s considered “substandard” varies from country to country, despite the fact that many countries adhere to international pharmacopeias.

“Unregistered” drugs are “not granted market authorization in a country.” Unregistered drugs are also often substandard, and distributed outside the normal, regulated distribution channels.

FDA Law Blog applauds the IOM efforts, but identifies some problems in turning the recommendations into reality. Here are two:

Creating a centralized public database of suspended and revoked wholesale pharmaceutical licenses in collaboration with existing state licensing boards would be a “one-stop shop” for the public good, but how the FDA would implement such a large program is unknown. The Prescription Drug Marketing Act (PDMA) already supports a state system of wholesale and manufacturer licensure, but there’s no federal licensure system. And the FDA would have to rely on the states to provide timely data.

Creating a mandatory track and trace system an old idea that has gone nowhere. “We can only imagine,” says FDA Law Blog, “the regulatory quagmire and backlash from industry trying to comply with a federal pedigree, along with myriad state pedigrees.”

Stronger regulation and quality oversight in other countries can only benefit the quality of products coming into the U.S., and progress toward a global solution to an increasingly global problem would be encouraging.

But until there’s a strong and sustained global effort to regulate the quality and delivery of prescription drugs, patients should do what they can to ensure they’re getting what they’re supposed to be getting. To learn how to buy and use medicine safely, see the FDA’s guidelines. And see our recent blog about the risks of buying drugs online.

Benzodiazepines are strong drugs prescribed for a range of problems, including lung disease, depression and anxiety. Adverse outcomes, including life-threatening side effects, have been associated with benzodiazepines, but until now there has been little data on how frequently these drugs are prescribed, and who uses them.

As reported on ScienceDaily.com, a study recently published in the journal Drugs and Aging helps to define the scope of benzodiazepine use by older adults with chronic obstructive pulmonary disease (COPD). And the results are unsettling.

Many brand names in the benzodiazepine class are familiar: Valium, Xanax, Klonopin, Ativan and Ambien are members. They’re so well known, they were the subject of banter between the two troubled lead characters in the movie “Silver Linings Playbook.”

In Canada, where the study was conducted, COPD (also known as emphysema or chronic bronchitis) affects 5 to 10 people in 100. Often, it’s caused by smoking. Despite the fact that, according to ScienceDaily, the guidelines of the American Thoracic Society/European Respiratory Society recommend that COPD patients not use benzodiazepines because of potential respiratory-related side effects, "I see a large number of COPD patients taking this medication class to help relieve disease-related symptoms like insomnia, depression and anxiety," said the study’s lead author.

The side effects, he said, include memory loss, decreased alertness, falls and increased risk of motor vehicle accidents.

The study examined more than 100,000 adults older than 65 with COPD to see how many new benzodiazepines were dispensed and the severity of each patient’s pulmonary symptoms while on the drug.

Dispensing new benzodiazepines was common—more than 1 in 3 adults got new meds. The more severe the symptoms, the higher the use of the drugs. Those with the most severe symptoms had the highest number of repeat prescriptions and early refills.

Benzodiazepines also were dispensed to patients experiencing flare-ups of COPD.

"These findings are new and they are concerning because they tell us that the patients most at risk to be affected by the adverse effects of this drug are the same ones that are using it with the most frequency," the authors said "This medication could be causing harm in this already respiratory-vulnerable population."

Benzodiazepines can be effective as a sleep aid, but they have been found to affect breathing ability and oxygen levels at night. Generally, their use should be infrequent, measured and only after a complete discussion with your doctor about the harms as well as benefits, especially if you are older or suffer from lung problems.

If you take one of these drugs and experience an adverse event, report it to the FDA’s data collection site MedWatch by linking here or calling (800) 332-1088.

Innumerable websites offer information about medicines that pregnant women can take safely. But because evidence is limited about many of the drugs listed and because the advice about them is inconsistent, the journal Pharmacoepidemiology and Drug Safety conducted a review to see if their guidance is reliable.

Guess what? In many cases, it’s not. And half of the websites examined didn’t include the key message that women should talk to their doctors about using medicine during pregnancy.

The Centers for Disease Control and Prevention (CDC) has summarized the most important elements of the study.

Half of all women of reproductive age look for health information on the Internet. More than 9 in 10 women use at least one medicine during their pregnancy, and about 7 in 10 of them use at least one prescription medicine. But almost none of the medicines had sufficient data to assess the risk for birth defects.

In the journal study, 25 active Internet websites listed medicines reported to be safe for use in pregnancy. The researchers tried to find out if there was scientific evidence to support this conclusion. Of the 245 medicines listed as pregnancy safe on these websites, about 4 in 10 didn’t have enough data to make that claim.

That doesn’t mean a medicine isn’t safe, but it might be. The point is that no pregnant woman should take any medicine, over the counter or prescription, if she doesn’t discuss it first with her doctor. That includes dietary or herbal supplements, which aren’t regulated by the FDA. If you’re planning to become pregnant, discuss the need for any medicine with your doctor before you conceive. And if you’re pregnant and taking medicine, don’t stop without first consulting your doctor.

Some medicines are notorious for causing birth defects. They include thalidomide (Thalamid) and isotretinoin (Accutane). They should be not be taken by anyone who is or might become pregnant.

Although some medications are known to be harmful when taken during pregnancy, according to the CDC, the safety of most medications taken by pregnant women has been difficult to determine because of certain variables:

• how much medication was taken;


• when during the pregnancy the medication was taken;


• other health conditions a woman might have;


• other medications a woman takes.

As the CDC notes, part of the problem in determining pregnancy-safe meds is the approval process. When the FDA tests medications to ensure their general safety and effectiveness, it doesn’t usually include pregnant women because of possible risks to the fetus. That’s why websites cannot make safety claims with authority for many medications.

The CDC suggests several resources where you might be able to find out more about the possible effects a medication might have when taken during pregnancy:

The Organization of Teratology Information Specialists (OTIS) has information about the risks and safety of taking medications during pregnancy and while breastfeeding. OTIS also conducts studies of pregnant women who contact them after having taken certain medications.

Drug companies sometimes conduct special studies using pregnancy registries. They enroll pregnant women who have taken a certain medication. After they give birth, the health of their babies is compared with the health of the babies of women who did not take the medication. For a list of current pregnancy registries and how to enroll, link here.

National Birth Defects Prevention Study is sponsored by the CDC. It works to identify possible risk factors for birth defects, including the effects of taking certain medications during pregnancy. For more information, link here.

Drug companies are required to report any problems with medications to the FDA. Health-care providers, researchers and the public also may report problems directly via the FDA’s MedWatch program.

Also, visit the CDC’s site for pregnancy and medications, and our backgrounder on prenatal care.

As we reported last year, part of the Obama administration’s health-care reform includes the Physician Payments Sunshine Act. It requires drug companies to disclose payments they make to doctors for research, consulting, speaking, travel and entertainment. Sometimes, such compensation influences treatment decisions and encourages overuse of drugs and devices. And these relationships are ripe for conflicts of interest.

So where are we in this process of finding out who’s getting what from whom?

According to the public interest news site ProPublica.org, things are moving slowly, but they’re moving. Final regulations were announced last month, but the release of payment data won’t happen until September 2014. The information was supposed to become public beginning this year, but since federal officials released the proposed regulations in December 2011, they’ve been collecting and analyzing comments about them.

Either there was a tsunami of comments, or the government is a bit tardy.

The first group of data to be released reflects payments made from August to December of this year. The reporting companies must turn the data over to the government by March 2014, then doctors have 45 days to review it for accuracy before it becomes public. Companies must report every year.

The information helps patients find out if their doctors receive money from any companies whose products they prescribe. If they do, these docs might be influenced to treat their patients in a way that might not be in the patients' best interests.

Until now the only similar resource has been a ProPublica initiative, Dollars for Docs. It has tracked payments since 2009 from a dozen drug companies, most of which were required to post the information on their websites as part of lawsuit settlements with the federal government. Mostly, the companies allegedly engaged in illegal marketing practices, such as off-label promotion. That’s when they promote a drug or device for a treatment purpose for which it hasn’t been approved by the FDA. Such settlements total billions of dollars.

Soon, Dollars for Docs will be updated through 2012 and include payment info from 15 companies.

Everyone—drug companies, lawmakers and consumer advocates—has been frustrated with how long it has taken the Centers for Medicare and Medicaid Services (CMS) to release the final rules for collecting and publishing the data. But at least it’s happening.

Any payment larger than $10 made to a U.S. physician or teaching hospital must be reported by date of payment and include a description of the service provided, the amount paid and which company products the payment involved. Speaking fees, consulting payments, research, gifts, food, entertainment, honoraria, research grants, royalties and license fees are included.

Fines for failure to report range from $1,000 to $10,000 for each incidence. A deliberate failure to report can cost $1 million.

According to ProPublica, some practitioners are rolling in the payment (graft?) green.

One Los Angeles-area doctor got more than $300,000 in speaking fees in 2009 and 2010 alone just from the companies in its database. Those businesses account for less than half of all U.S. pharmaceutical sales, so who knows how much more dough is in promotional play?

It’s interesting—dismaying?—to note that more than 250 physicians who were drug company speakers and consultants had been disciplined by their state medical boards or other regulatory agencies.

Find out if your physician is one of them at the Dollars for Docs link.

If you played a coin-flipping game where you could show all your winners and hide your losing tosses, you'd be way ahead. But nobody would let you get away with that, would they? If you're Big Pharma, you get away with hiding the evidence every day, as Dr. Ben Goldacre explains in an op-ed in the New York Times.

Drug companies developing new products get to run their own tests and publish only the results they like. Independent audits are few and far between.

This well known scandal was supposed to have been cured in 2007 when a new law required that the results of every clinical trial of a drug be published within one year of completion, or face a fine of $10,000 a day from the FDA. But as Goldacre reports, the first audit of this law was published in 2012 and found that four of every five trials had ignored the reporting requirements.

How many fines have been issued since the start of the new law?

Zero.

Goldacre also reports that a pledge of medical journal editors back in 2005 to never publish drug trial results unless the study had been publicly registered at its outset (to solve the same "bury the bad evidence" problem) has also failed to work. More than half of published research studies since then have not been properly registered, according to one audit.

Why is this bad for patients? Because we don't really know if the expensive drugs we take really work. And we'll never know unless each and every clinical trial that starts gets published when it ends.

Despite efforts by the government and conscientious health-care facilities to promote the proper prescribing and administration of medicine, the incidence of hospital medication errors is more frequent than believed, according to new research published in the journal Critical Care Medicine.

Possibly even more disappointing is that patients and their families often aren’t told when such a mistake occurs.

As described in a story on AboutLawsuits.com, the study found that when an error occurred, not only weren’t the people affected notified, more than half the time no corrective action was taken after the mistake was discovered.

Researchers at Johns Hopkins University School of Medicine in Baltimore analyzed nearly 840,000 medication errors that happened in 537 hospitals across the country. Both regular care wards and intensive care units (ICUs) were studied. More than 750,000 errors were reported, and more than 9 in 10 of them occurred in wards other than intensive care. So the sheer number of mistakes doesn’t necessarily appear to be a matter of the urgency or extreme condition of the patient.

But the gravity of the errors does appear to be related to critical conditions. Mistakes that caused the most harm or resulted in the patient’s death did occur in the ICU at twice the rate of non-ICU wards.

“Consideration should be given to developing additional safeguards against ICU errors,” the study authors concluded, “particularly during drug administration, and eliminating barriers to error disclosures.”

As explained by AboutLawsuits, the data was collected for the years between 1999 and 2005 from MEDMARX, a program for anonymous, confidential reporting of medication errors. It’s a self-reported system, which makes the results of this study even more alarming. How many errors weren’t reported because they didn’t have to be?

Most of the mistakes happened when the medicine was being administered, as opposed, for example, to a contaminated or missed medicine, although failing to give a patient a scheduled medicine was common.

The most harmful errors involved problems with a dispensing device, such as an IV line. Giving someone the wrong dose also was a significant problem.

Although patients and their loved ones often weren’t told that a medication mistake had been made, neither was 1 in 3 hospital staff members who had made the mistake, at least not immediately after they’d done so.

To learn more about the types of medication errors, see our backgrounder. To learn how to protect a loved one in the hospital, see my newsletter here. To learn how to have or help someone have a safer hospital experience, see my newsletter here.

With the constant appeal of “get a flu shot” echoing throughout the news media, and with so many Americans reeling with the flu, you begin to wonder what you’ll do if you fall victim.

One thing you might consider, but probably should reconsider, according to Dr. Harlan M. Krumholz writing on Forbes.com, is Tamiflu.

Krumholz, professor of Medicine and Epidemiology and Public Health at Yale University School of Medicine, says we don’t know enough about the effectiveness and safety of Tamiflu, and Roche, its manufacturer, isn’t telling.

Flu can make you miserable, with fever, chills body and headaches, a host of respiratory issues and the general sense that you must’ve gotten hit by a truck, except where’s the truck? Unlike a bad cold, flu generally comes on fast and hard; and colds aren’t associated with the extreme body and joint aches you get with flu.

For some people, flu can be life-threatening, especially the very young, very old, people with immune or pulmonary (lung) problems, cardiovascular disease, diabetes, the obese and people younger than 19 who are on long-term aspirin therapy. But even if you’re healthy as a horse (and why they’re healthier than people we have no idea), you really don’t want to get the flu. And if you do, you want to minimize its symptoms and shorten its course.

That’s what Tamiflu, an antiviral agent, promises to do. And a lot of custodians of public health, apparently, believe its promoters—the U.S. reportedly stockpiled $15 billion of Tamiflu not so long ago before a vaccine for H1N1 was developed and fears of an outbreak were widespread.

Tamiflu, whose generic name is oseltamivir, is prescribed for people older than 1 if they’ve have had symptoms for a couple days, to prevent flu if they’ve been with someone who has the flu or sometimes when there’s an outbreak. It’s supposed to stop the spread of the flu virus in the body and shorten the time you have symptoms.

Because Tamiflu battles a virus, it won’t do anything if you have a bacterial infection, which can be a complication of the flu.

But, says Krumholz, Roche won’t divulge all the relevant data it has about its drug. Cochrane, an organization that reviews scientific evidence and analyzes it to assess the value of medical interventions, recently updated its Tamiflu file. Here, says Krumholz, are five things you should know about that examination.

1. The manufacturer of the drug sponsored all the trials. That calls into question the objectivity of the results—if you want to sell something, you have an interest in making sure the drug trials show what you want them to. And, says Krumholz, “reviewers found evidence of publication and reporting biases.” There were no controlled trials conducted by independent sources.

As Krumholz notes, industry trials can be well conducted, but lack of independence has been known to influence study design and what results are released, meaning they probably are designed to have the best chance of showing benefit and the results that are released are probably selective. One of the Cochrane study authors found that 60 percent of the randomized data from Tamiflu trials on people with flulike illness symptoms have never been published, including the biggest trial ever conducted.

You have to wonder: What are they hiding?

2. The studies did not show that Tamiflu reduced the risk of being hospitalized. One reason people might take an antiviral is to prevent the illness progressing to the point where they would need this level of care. There was no evidence that the drug produced that benefit.

3. The studies were inadequate to determine the effect of Tamiflu on complications. Other than hospitalization, people may think Tamiflu would prevent other complications, such as bacterial infections, but the reviewers found that the way the drug trials were designed and reported were too limited to make any conclusions about effects of the drug on complications. “To expect that Tamiflu can reduce complications would be a leap of faith currently unsupported by the available evidence,” Krumholz writes.

Also, the FDA requires Roche to print on the label: “Tamiflu has not been shown to prevent such complications [as serious bacterial infections].”

4. The studies were inadequate to show if Tamiflu could reduce the chances of a sick person transmitting the virus to someone else. One of the Cochrane study authors said, simply, that Roche did not design the trials to answer the question of transmission. The trials, and the FDA’s approval of Tamiflu, were based on the drug’s ability to reduce the chances of “symptomatic influenza.” Because no one knows anything about asymptomatic influenza infections, no one can say if Tamiflu reduces transmission of the virus.

5. The use of Tamiflu did reduce the duration of flu symptoms—by about one day. Several studies showed this, but the duration of symptoms varied a lot among all the different studies the reviewers examined. So if some subjects had symptoms that lasted three days and some subjects had symptoms that lasted two weeks, a day might be meaningful the first group and barely noticeable by the second.

The Cochrane reviewers asked Roche for full clinical study reports so that they could make a more conclusive report about Tamiflu. Roche declined to cooperate. “People face decisions every day about this drug,” Krumholz writes, “and more than ever this season, so it would seem reasonable that the company would share all that they know about the drug.”

According to the National Institutes of Health, some of the lesser side effects of Tamiflu/oseltamivir include:

• nausea


• vomiting


• stomach pain


• diarrhea


• headache

• rash, hives, or blisters on the skin


• itching


• swelling of the face or tongue


• difficulty breathing or swallowing


• hoarseness


• changes in behavior

Is Tamiflu worth taking? Why is Roche unwilling to share information? Should doctors keep prescribing medicine when “potentially vital” information is being withheld? All questions Krumholz asks, and so should the rest of us.

People who take medication to help them get to sleep and stay asleep have always been cautioned about its potential for addiction and side effects ranging from the minor to the serious. Last week, the FDA deemed one class of this medication so dangerous that it’s requiring manufacturers to reduce its dosage.

As reported on NPR, Ambien, its generic versions and similar sleeping pills (AmbienCR, Edluar and Zolpimist) must reduce the amount of their active ingredient, zolpidem, because it remains in the body longer than had been thought. That means people who take a pill to sleep might be dangerously drowsy the next day.

Side effects of sleeping drugs range from headaches, dry mouth and constipation to trouble concentrating, dizziness and rebound insomnia. That’s when you stop taking a drug and the problem you originally took it to address returns, only worse.

Daytime sleepiness has long been a sleeping pill hazard, and, it turns out, Ambien and its fellow pharmaceutical travelers, carry an extreme risk, to the point of making driving and operating machinery hazardous. The FDA has gotten about 700 reports of people getting in traffic accidents after taking these drugs.

The concern is most acute for women, because the drug stays in their bodies longer than it does in men.

The FDA has required the dose for women to be reduced by half--from 10 milligrams to 5 milligrams for immediate-release products (Ambien, Edluar and Zolpimist), and from 12.5 milligrams to 6.25 milligrams for Ambien CR, an extended release pill.

Manufacturers also must change the products’ labels on the drug for men, for whom FDA also has recommended lower doses.

Ellis Unger, director of the FDA’s Drug Evaluation and Research, said "Patients who must drive in the morning or perform some other activity requiring full alertness should talk to their health care professional about whether their sleep medicine is appropriate."

Unger told NPR that although other popular sleeping pills, including Lunesta and Sonata, have different active ingredients and are not subject to the warning and reduced dosage, the FDA is looking at their safety as well.

The New York Times reported that in 2011 about 60 million prescriptions for sleeping medication were dispensed; about 40 million were drugs containing zolpidem.

In addition to the common side effects, The Times noted some other strange behavior attributed to the drugs--texting, eating or having sex during the night without any memory of it in the morning.

Some people who are dependent on sleeping medication may have difficult tapering off of it. If you take a zolpidem drug, FDA officials recommend continue doing so for now, but talk to your doctor about altering the dose. Doctors will still be able to prescribe the higher dosage, according to The Times, if the lower dose does not work.

The FDA has a list of questions and answers for patients about Ambien and other drugs including how to treat insomnia, what are the over-the-counter options, what are the effects of other classes of sleeping pills and how to decrease your risk of next-day drowsiness if you take sleeping pills. Link here for the complete discussion.

Last year we wrote about a report issued by the Centers for Disease Control and Prevention, “Grand Rounds: Prescription Drug Overdoses — a U.S. Epidemic.” Powerful painkillers continue to be overprescribed, abused and mismanaged by doctors, as told in horrifying detail in an ongoing series by the Los Angeles Times.

The FDA, in acknowledgment of so much going wrong in the prescribing and use of opioids, will begin holding public hearings next month. Better late than never, considering that:

• Prescription drug abuse is the fastest growing drug problem in the U.S.


• In one recent year in the U.S. one death due to drug overdose occurred every 19 minutes.


• The recent increase in unintentional drug overdose deaths has been driven by the increased use of prescription narcotics.

As reported on AboutLawsuits.com, FDA officials will consider the diagnosis and understanding of patient pain; methods professionals use to distinguish various types of pain; definitions for terms such as mild, moderate or severe in diagnosis. Specific drug concerns, such as product composition, abuse deterrence, dosage controls and prescribing practices are also key.

Many opioid drugs, including Vicodin, Oxycontin and Methadone, are abused not only by medical patients, but street users. AboutLawsuits says that officials hope to find balance in minimizing drug abuse while preserving access to such drugs by patients with a legitimate need.

Beauty’s only skin deep, but for many people who take prescription drugs, appearance apparently strengthens the bonds of belief. According to a recent study in Archives of Internal Medicine, people who receive generic drugs whose color varies from one prescription to the next are more than half as likely to stop taking the medicine.

That can mean losing out on a drug's healing power, all because of its color.

As reported on ScienceDaily.com, more than 7 in 10 drug prescriptions are generic versions of brand name pharmaceuticals. Generics are the bioequivalent of the patented version; that means that although they might be formulated differently from the brand drug, their active ingredients are the same and they are broken down and used by the body in the same way. But generic drugs usually look different from the brand version in shape, color and size.

Most prescriptions require that the medicine be taken according to a certain regimen. Some medicine should be taken at the same time each day, some should be taken with food or on an empty stomach. Some, like antibiotics, must be taken until the prescription is exhausted, even if the symptoms of the infection have subsided. Taking one’s medicine as one is supposed to do is called “compliance” or “adherence.” In many cases, the inability or unwillingness to comply with the regimen can have adverse effects, and sometimes failing to comply can be dangerous or even life-threatening.

As one of the study’s researchers told ScienceDaily, “Pill appearance has long been suspected to be linked to medication adherence, yet this is the first empirical analysis that we know of that directly links pills' physical characteristics to patients' adherence behavior. We found that changes in pill color significantly increase the odds that patients will stop taking their drugs as prescribed."

Studying patients on anti-epileptic drugs, the researchers compared the odds that those who didn’t refill their meds had been prescribed pills that looked different from those in a previous prescription. The researchers compared their subjects with entries in a national database of filled prescriptions.

Interruptions in filling prescription occurred significantly more frequently if the pills were of a different color. As ScienceDaily noted, interruptions in anti-epileptic drug use for even a few days presents an increased risk of seizure.

There are lots of reasons why people fail to comply with any medical treatment regimen. It might be uncomfortable, inconvenient, or cause unpleasant side effects. Sometimes they just forget. This study’s authors acknowledged that medication adherence can be complicated. But they suggest that if measures were taken to permit—or even require—bioequivalent pills to be manufactured with a similar appearance, brand or generic, it might boost patient adherence.

The message for physicians is to explain to their patients when prescribing pills that they might look different from refill to refill. Pharmacists should inform consumers that a change in supplier can result in a change of appearance, but that the medicine is the same.

And patients, as always, should know the name of the drug they’re taking, its intended effect and how long they should expect to wait to see results. They should also ask the doctor and/or the pharmacist about potential side effects if those practitioners have not offered that information.

GlaxoSmithKline paid $3 billion.

Abbott Laboratories paid $1.4 billion.

Pfizer paid $2.3 billion.

Eli Lilly paid $1.4 billion.

And now, Amgen will pay $762 million for, as a U.S. attorney in New York said last month, “pursuing profits at the risk of patient safety.”

Yes, folks, once again a major player in the pharmaceutical industry has been caught engaging in criminal behavior, thanks in part to a former employee who couldn’t tolerate its utter disregard for the law, and blew the whistle.

We regularly cover the misdeeds of Big Pharma (here, here and here), and everyone aware of this history of settlement payments understands that to the drug industry, they’re merely the cost of doing business.

The Amgen settlement, as reported by the New York Times, resulted from federal charges to which Amgen pleaded guilty. The company illegally marketed Aranesp, which is approved by the FDA for chemotherapy patients. But that wasn’t enough for Amgen, who promoted it to treat anemia in cancer patients. That’s an “off-label” use, or one for which the medicine was not approved.

Amgen also was charged with promoting larger doses of Aranesp than the label directed. That enabled the drug to be used less frequently, which, according to The Times, made it more attractive to doctors and patients than a rival’s anemia drug.

Doctors are allowed to use drugs for off-label use, but companies may not promote them.

Clearly, Glaxo, Abbott, Pfizer, Lilly, Amgen and who knows how many others don’t care. These companies believe the rules were written for everyone but them. Amgen had tried to obtain FDA approval for the less frequent dose, but was denied. The FDA called the company’s studies inadequate. So what? was Amgen’s response--according to federal charges, the company continued to promote the off-label dosing after the denial.

One federal prosecutor told a judge, The Times reports, that “in certain instances, Amgen employees were so thoroughly indoctrinated to sell the drug for off-label uses that they did not, in fact, know that the drug had not been approved for the use for which they were selling it.”

Sales representatives, according to The Times, were not supposed to initiate discussions of off-label uses, but they were trained in ways that would prompt doctors to ask certain questions that opened the door for the reps to offer the docs “studies” supporting the off-label use. Amgen calls this approach “reactive” marketing. Federal prosecutors called it illegal.

A story in the Los Angeles Times recounted how one former Aranesp product manager filed suit against Amgen, alleging that, among other inducements to use the product, it gave “liquid kickbacks” to doctors. She charged that Amgen overfilled vials of Aranesp so doctors got more medicine without paying the additional cost. She said the company encouraged the docs to bill Medicare and private insurers for the surplus, thereby scamming the system and lining their pockets.

Why does Big Pharma continue to get away with criminal behavior? Because the fines, as huge as they are, don’t begin to threaten the companies’ huge profits—at one point, Aranesp earned Amgen more than $4 billion a year. Critics, according to the New York Times, say that the companies won’t be deterred until their executives are held personally responsible.

The U.S. attorney said that there was insufficient evidence to charge individuals at Amgen. But the company did agree to sign a corporate integrity agreement requiring execs and board members to personally certify compliance with regulations, which would make it easier to prosecute individuals if the company violated the law again.

Not that it’s suitable redress for Amgen’s despicable behavior, but Aranesp, which once was Amgen’s biggest seller, has declined in popularity. Studies, the New York Times says, show that high doses can lead to blood clots and the worsening of cancer. Sales of Aranesp in the first nine months of 2012 were $1.55 billion.

Prescription drugs undergo scientific and regulatory scrutiny for the simple reason that they are dangerous when not used properly … and sometimes even when they are. Because they pose a threat to public health and the environment, there’s a proper way to dispose of them when they have expired, go unused or no longer are needed.

Because pharmaceutical companies manufacture prescription medicine and because they’re the ones that profit from them, a California law demands that they operate and subsidize a program enabling consumers to turn in unused meds for proper disposal. Is anyone surprised that Big Pharma is fighting this law?

As reported in the New York Times, drug take-back programs generally are run by local or other government agencies. But there’s a building sense that the pharmaceutical industry should assume the responsibility.

Unused and/or unneeded medicine is dangerous to curious small children (see our post about drug-poisoned kids), to teenagers seeking the thrill of experimentation, to drug abusers and because criminals see it as a commodity to be traded or sold. Pills or other medicine flushed down the toilet has been shown to pollute drinking water and disturb the ecosystem.

Various drugs—antidepressants, antibiotics, heart meds and hormones—have been found in waterways. Sewage and drinking water treatment facilities are not designed to remove pharmaceuticals, and trace amounts in drinking water probably aren’t harmful to humans. But larger amounts could adversely affect wildlife—The Times referred to a study that found the antidepressant Prozac in the brains of fish.

In the summer, Alameda County in the San Francisco Bay Area became the first locality to require drug companies to implement take-back programs. Manufacturers have until July 2013 to submit plans for doing so.

Always quick to protect its rights but less quick to do the right thing, the Pharmaceutical Research and Manufacturers of America (PhRMA), which represents brand-name drug companies, the Generic Pharmaceutical Association and the Biotechnology Industry Organization filed a lawsuit earlier this month to have the law struck down.

Big Pharma claims that the ordinance violates the Constitution in authorizing a local government to interfere with interstate commerce. One of its spokesmen told The Times, “This program is one where the cost is shifted to companies and individuals who are not located in Alameda County and who won’t be served by it.”

He said the program would cost millions and that pharmaceutical companies were “not in the waste disposal business.” (This reminds us of an old Tom Lehrer song satirizing a German-American rocket scientist: “ ‘Once zee rockets are up, who cares where zey come down? Zat’s not my department,’ says Wernher von Braun.”)

The president of the Alameda County Board of Supervisors told The Times, “It’s just unfortunate that PhRMA would fight this because it would be pennies for them.”

The company take-back program idea is hardly new: Three Canadian provinces have take-back programs subsidized by the pharmaceutical industry, The Times reports, and seven U.S. state legislatures have introduced bills to require drug companies to pay for take-back programs in the last few years. None has passed, but Scott Cassel, founder and chief executive of the Product Stewardship Institute, a nonprofit group that advocates such programs, told The Times that scores of similar “extended producer responsibility” laws have been enacted in 32 states for other products, such as batteries and mercury-containing thermometers. He was unaware of any that had been struck down on constitutional grounds.

If you have drugs in need of disposal, don’t flush them down the toilet or put them in the trash. Pharmacies generally accept unused drugs, and can advise you how to dispose of leftover drugs safely.

Last week a federal appeals court made a ruling that chips away at a fundamental aspect of the FDA's gatekeeping function with new drugs. The court tossed a conviction of a drug sales representative who was promoting drugs for uses the FDA had not approved. Two of the three judges on the panel said such restriction was a violation of the drug rep’s first amendment rights.

“Off-label” use of drugs is not illegal—doctors often prescribe a medication for a purpose other than what is specifically approved by the FDA. But pharmaceutical companies are prohibited by law to advertise or market them for such “customized” purposes. Because doctors understand the individual needs of their patient, they are in a unique position to know when off-label use might be appropriate—sometimes, such treatment is part of the art of medicine.

Big Pharma appreciates this art not because it’s creative and useful, but because it sells product.

A story in the New York Times said the court’s ruling “could have broad ramifications for the pharmaceutical industry.”

No kidding. Many companies have suffered huge financial penalties when they got caught and punished for off-label promotion. As we wrote in July, GlaxoSmithKline agreed to fork over $3 billion for promoting the antidepressant Paxil for treating depression in children and adolescents despite reports of increased suicidal tendencies among teens who took the drug. It promoted Wellbutrin, also an antidepressant, for weight loss, substance addiction, attention deficit hyperactivity disorder (ADHD) and sexual dysfunction. Then, the sales reps’ description of it as “the happy, horny, skinny pill” was deemed illegal. Now, it’s a free-speech issue.

Another company, Johnson & Johnson, settled a consumer fraud problem for $181 million after it fudged the marketing of Risperdal, an antipsychotic drug.

John R. Fleder, an attorney who formerly represented the FDA, told The Times, “Most if not all of these cases have been based on a central premise: that it is unlawful for a company and one of its employees to be promoting a drug or a medical device off-label. And this decision hits at the heart of the government’s theory.”

This case involved Alfred Caronia, a former sales rep for Orphan Medical, later acquired by Jazz Pharmaceutical, and the drug Xyrem, which had been approved for narcolepsy, a sleeping disorder whose victims experience uncontrollable attacks of deep, if brief, sleep. Caronia allegedly promoted it to doctors as a treatment for insomnia, fibromyalgia (chronic musculoskeletal pain and fatigue) and other conditions. In 2005, The Times reports, he was taped discussing such uses with a doctor who was a government informant. He was convicted by a jury in 2008.

He appealed on the basis that his First Amendment rights were restricted illegally.

At least one of the appellate judges retained her wits. Dissenting Judge Debra Ann Livingston vigorously argued, according to The Times, that by tossing Caronia’s conviction “the majority calls into question the very foundations of our century-old system of drug regulation,” she said. “[If drug companies] were allowed to promote FDA-approved drugs for nonapproved uses, they would have little incentive to seek FDA approval for those uses.”

Gerald Masoudi, a former counsel of the FDA, tried to split the difference between a truthful discussion of off-label drug uses and a misleading or false discussion. He told The Times that anyone except pharmaceutical companies could discuss off-label uses, and that the ruling is significant “because it’s going to make FDA, in its promotion cases, focus on the kinds of speech that are more likely to harm consumers, such as false or misleading marketing versus something that is not approved.”

This isn’t over until it’s over, which might not be until the government decides whether to request a rehearing before a full panel of judges, and after that, it could land in the lap of the U.S. Supreme Court.

The only saving grace at the moment, as noted in The Times’ story, is that because the ruling applies only within the Court of Appeals for the Second Circuit in New York, pharmaceutical companies that sell their wares far and wide won’t be making wholesale changes to their marketing policies. More likely is that the FDA will chill on the pursuit of similar cases until resolution.

The blood-thinning drug Pradaxa has starred in a long-running drama with hundreds of adverse event reports, scores of lawsuits and more than 500 deaths. Introduced in 2010 as an option to Coumadin (warfarin), Pradaxa is under fire for dire side effects including hemorrhage and internal bleeding, as we wrote earlier this year. Unlike older anti-clotting drugs, Pradaxa has no antidote for uncontrolled bleeding.

The latest chapter in this tale was told earlier this month by the New York Times, when the FDA released a report concluding that Pradaxa did not show a higher risk of bleeding than warfarin. As The Times noted, the report did not mention the lack of an antidote.

Medical professionals and patients alike have complained about Pradaxa, expressing concern that the approval process was insufficient, and that such a potentially dangerous drug should not be on the market without a way to reverse its unwanted effects. Pradaxa has made $1 billion for its manufacturer, Boehringer Ingelheim, but critics say it’s exemplary, as The Times puts it, “of what can happen when a drug that performs well in tightly controlled trials is released into the messy world of real-life medicine.”

The FDA report says that bleeding rates associated with Pradaxa don’t appear to be higher than those associated with warfarin. At the American Heart Association Scientific Session a week after the FDA report, Boehringer Ingelheim presented findings that, according to its news release, an antidote in development shows promise, and clinical trials are being initiated.

We have to ask: Didn’t they put the cart so far in front that you can’t even see the horse?

When reports began to surface of bleeding problems, Boehringer Ingelheim recommended dialysis to flush the drug out. Dialysis involves bypassing the kidneys to purify the blood through a machine. But the company, according to The Times, acknowledges that “the amount of data supporting this approach is limited.”

The boneheaded dialysis advice was described perfectly by one doctor in The Times’ story: “People that are bleeding to death aren’t going to tolerate being put on dialysis.”

The problem is compounded, according to The Times, if doctors prescribe the drug to the wrong patients. Older people and people with kidney problems are not good candidates for Pradaxa—their bleeding risks are higher than for other people. Boehringer Ingelheim advises testing a patient’s kidney function before prescribing Pradaxa, and notes that the risk of bleeding increases with age.

“The problem is that the people that prescribe this, as a general rule, are cardiologists and family practitioners,” Dr. Mark L. Mosley, director of the emergency room at Wesley Medical Center in Wichita, Kan., told The Times. “The people that see the harm are your E.R. docs and your trauma docs.”

When Pradaxa was approved, its lower maintenance seemed superior to the nearly 60-year-old warfarin (Coumadin) for preventing prevent strokes in people with atrial fibrillation (a heart-rhythm disorder commonly called A-fib). Warfarin patients must be carefully monitored for diet and drugs, and must have frequent blood tests. Not so for Pradaxa patients.

In little more than a year, The Times reports, 17 in 100 a-fib patients got Pradaxa; 44 in 100 got warfarin. The FDA estimates that in the U.S., about 725,000 patients have taken Pradaxa.

But in 2011, according to The Times, Pradaxa “was linked to more reports of injury or death than any of the more than 800 drugs regularly monitored by the Institute for Safe Medication Practices.”

Other new drugs intended as an option to warfarin (Xarelto, which has been approved to treat blot clots, and Eliquis, for which FDA approval is pending) also lack antidotes, but they haven’t shown the same bleeding-death risk as Pradaxa.

All medicine carries a risk of side effects; some can be life-threatening. Sometimes, the risk is worth it, which is the position adopted by medical professionals who believe in Pradaxa. The Times referred to a recent study showing that about 4 in 10 people with atrial fibrillation don’t take any drugs, leaving them at risk for strokes. Many cardiologists say the risk of stroke is more dangerous than the risk of bleeding complications.

Maybe. But if you’re an A-fib patient whose doctor recommends Pradaxa, find out why he or she prefers it to warfarin, which also can cause a host of side effects, some of them serious. If you’re older or have a history of kidney problems, beware, and seek a second opinion.

From the meningitis outbreak, something good may come out of something bad. Earlier this month, U.S. Rep. Edward J. Markey of Massachusetts introduced a bill in Congress to boost the federal government’s authority to regulate compounding pharmacies.

As we’ve been reporting in the last several weeks (most recently last week), compounding pharmacies have been able to operate in often sketchy ways without the kind of oversight necessary to protect patients from harm. As reported on FDA Law Blog, Markey’s bill, the Verifying Authority and Legality in Drug Compounding Act of 2012 (VALID):

• Ensures that compounding pharmacies operating as drug manufacturers are regulated by the FDA as drug manufacturers (they do not currently fall under FDA scrutiny).


• Preserves state regulatory authority for traditional small compounding pharmacy activities and the requirement that drugs are compounded per each patient’s prescription. The FDA may waive this requirement in the event of a drug shortage or to protect the public health or well-being, but not for longer than one year unless the Secretary of Health and Human Services deems an extension necessary.


• Increases transparency to the public by requiring compounded drugs to include this statement: “This drug has not been tested for safety and effectiveness and is not approved by the FDA. Serious adverse reactions to this drug should be reported to the pharmacy where it was received and the FDA at _____” (phone number and a website).

Pharmacists and pharmacies compounding a drug product are required to report to the Secretary of Health and Human Services (HHS) any adverse event associated with the use of it within 10 days after becoming aware of it. If a pharmacist or pharmacy knows of any kind of contamination, chemical or physical change or deterioration of a drug that has been distributed and “could cause serious injury or death,” the pharmacist has five days to report it to the Secretary.

Some compounding operations are excused from some of the Act’s provisions, but not pharmacies required to be registered as drug manufacturers. Pharmacies or pharmacists might be waived if they: work within a hospital system compounding drug products exclusively for its patients; compound sterile drug products; compound drug products in limited quantities before receiving a valid prescription for an individual patient in their state.

As noted on FDA Law Blog, Markey, whose district is home to the New England Compounding Center (NECC) that distributed the contaminated steroid medicine that caused meningitis, said the VALID Compounding Act would close the “regulatory black hole.”

Additional developments in the NECC case were reported last week by the Boston Globe.

First, Massachusetts regulators ordered all the pharmacists and technicians employed by the NECC to stop working in the drug-compounding industry. That indicates, the paper said, that state regulators are concerned that the workers failed to follow proper procedures.

Duh. A letter from the Massachusetts Board of Registration in Pharmacy obtained by The Globe said that pharmacy staff “may present an immediate or serious threat to the public health, safety, and welfare and should immediately cease.”

The state board had already decided to seek surrender of NECC’s license. And the outfit shut down last month and recalled all of its products.

Later in the week, The Globe reported that the director of the state pharmacy board was fired and the board’s attorney placed on administrative leave for allegedly ignoring a complaint in the summer that NECC was distributing bulk shipments of drugs to hospitals in Colorado. That violates its state license.

NECC has long been a problem. As the Globe noted, The Colorado Board of Pharmacy issued a cease and desist order to the pharmacy in April 2011 after discovering its “unlawful distribution of prescription drugs.” This summer, when a Colorado hospital discovered a bulk shipment of a drug from NECC, Colorado authorities notified their Massachusetts counterparts.

They blew it off.

The House of Representatives’ Energy and Commerce Committee is convening public hearings Nov. 14 about the problems at NECC.

As many people know, grapefruit is a delicious and healthful fruit that can be very bad medicine when consumed with certain drugs. One of its chemical constituents, furanocoumarin, interacts with a variety of drugs that can enhance or diminish their effects. Among the more common drugs not to be consumed with grapefruit are those taken for high cholesterol (Lipitor, Zocor), high blood pressure (Plendil, Procardia), anxiety (Buspirone), depression (Zoloft) and seizures (Carbatrol, Tegretol).

Like grapefruit, many dietary supplements seem benign, but also might pose health risks when taken in the company of certain prescription drugs. A study published recently in the International Journal of Clinical Practice concluded that although interactions between drugs and herbs and dietary supplements (HDS) affect relatively few medications, health-care practitioners should be certain to address the issue when prescribing drugs to patients to avoid adverse events. We would add that patients should inquire about their safety.

More than 1 in 4 adverse incidents documented in the study were classified as “major” events. Complications included heart problems, chest and abdominal pain and headaches.

Medications affecting the central nervous system or cardiovascular system had more documented interactions with HDS. Flaxseed, Echinacea and yohimbe were more likely to cause problematic side effects when taken with drugs than were vitamins and minerals.

Researchers studied 1,491 unique pairs of HDS-drug interactions, 213separate HDS and 509 medications. They documented 882 negative interactions. HDS products containing St. John’s wort, magnesium, calcium, iron and ginkgo notched the most interactions with medications. Among the drugs, warfarin (Coumadin), insulin, aspirin, digoxin (Digitek, Lanoxin), and ticlopidine (Ticlid) had the most interactions with HDS.

As noted on AboutLawsuits.com, nearly half of all patients with chronic diseases who use prescription drugs also take herbs or dietary supplements. The latter are not regulated by the FDA. AboutLawsuits referred to a report by consumer watchdog Public Citizen that determined there was little benefit to healthy adults in taking HDS. Like many scientists, Public Citizen advocates for greater regulatory oversight of dietary supplements.

But the lack of systemic review of the industry and its products’ effects on human health does not excuse doctors and patients from taking responsibility for what they prescribe or consume, respectively. We’ve written about the folly of vitamin supplementation, and our newsletter “Eat, Drink and Be Wary: The Truth About Diet Supplements and Sports Drinks” offers a wider discussion.

Make sure your doctor has a full record of all medicines—prescription and over-the-counter—you take, as well as any vitamins, minerals or dietary supplements. If you are prescribed a new drug, remind him or her of what you take, and ask if it’s safe to take them with the new medication.

As the death toll continues to rise from the meningitis outbreak after a compounding pharmacy distributed contaminated medicine a few months ago, how these facilities operate has come under increased scrutiny. A story published last week in USA Today detailed how compounding pharmacies escape regulatory punishment and end up paying for their mistakes only through lawsuits by injured patients for damages.

“In some cases,” the paper reports, “there's almost no penalty for pharmacies that break the rules, and the people who run them simply continue with business as usual, sometimes with tragic results.”

Compounding pharmacies “customize” medicine—they combine various ingredients to create products specific to individuals or discrete markets, but for regulatory purposes are not considered manufacturers. (See our recent post about how compounding drugs are made.)

According to USA Today, since 1990 the FDA has recorded about 200 adverse events associated with 71 compounded products.

In its review of state and federal legal and regulatory documents, USA Today tracked contaminated, adulterated and mismeasured products, and some that were counterfeit or illegal. Many compounding pharmacies went out of business not for their failure to uphold regulatory standards, but because they got sued for their skanky wares.

Personal injury lawsuits are an avenue for reparation by people who have been harmed by wrongdoing and malfeasance, but they’re hardly a substitute for governmental control. As Joanne Doroshow, executive director of the Center for Justice & Democracy at New York Law School told USA Today, civil lawsuits help “to make sure the most dangerous compounding pharmacies are forced out of business. Nothing else seems to be doing it … because the entire regulatory system lacks teeth."

Three such lawsuits have been filed against the Massachusetts pharmacy responsible for the current meningitis crisis. That number is decidedly preliminary.

The public hammer also fell: The Massachusetts Board of Registration in Pharmacy revoked the pharmacy’s license and those of three of its pharmacists. Among the cases reviewed by USA Today, it’s the only time a state permanently revoked a pharmacy’s license. And that’s pretty much the extent of the civil punishment the government can mete out. The Massachusetts state board is not empowered to issue fines for wrongdoing.

Criminal prosecution by the FDA and U.S. Justice Department remains a possibility, but it’s remote—it’s legally difficult to hold pharmacists accountable for deficient drugs they produce or dispense. Conflict of interest also might play a role.

Former FDA compliance officer Sarah Sellers told USA Today that she can’t recall another case in which a state closed a compounding pharmacy permanently, possibly because members of state pharmacy boards often operate or have interests in compounding pharmacies. "If there is conflict of interest at the state level, that may be a contributing factor in the lack of enforcement," Sellers said.

The paper recounts a story from 10 years ago of a meningitis outbreak in North Carolina due also to a contaminated injectable steroid produced by Urgent Care Pharmacy, a South Carolina compounding facility. After finding poor sanitation and deficient quality-control practices, state and federal investigators ordered it to cease selling the contaminated drug, and issued warnings to 11 states where they had been distributed.

The South Carolina Board of Pharmacy levied a $10,000 fine, shut it down until the pharmacy corrected its deficiencies and suspended the license of the pharmacist in charge.

Urgent Care declared bankruptcy a few months later in the wake of several lawsuits by victims who had been injured by the drug. But the pharmacist whose license was suspended was allowed to continue working on a probationary basis; he now works at another South Carolina pharmacy and his record, USA Today reports, shows him “in good standing” with “no disciplinary action.”

Forest Horne, a lawyer who represented the family of a woman who died after receiving a contaminated injection, told USA Today "The regulatory system failed. If that guy is able to go back and work in a pharmacy … I think the regulatory system is not working, because the conditions in that plant were absolutely abysmal.

"If these people aren't stopped through litigation, they're not going to be stopped."

This is no way to promote best medical practice and ensure patient safety. Litigation takes a long time and isn’t always successful. And we haven’t even touched on the topic many people find most troubling about free-wheeling compounding pharmacies: their role in producing and distributing illegal drugs.

In antiquity, people chewed willow bark for its analgesic properties. Willow is rich in salicylate, the precursor to acetylsalicylic acid, the compound delivered today by common aspirin. It not only relieves pain, it reduces inflammation and fever. And within the last generation, aspirin has become the only over-the-counter analgesic that some health professionals have recommended to lower the risk of heart disease and stroke.

But the October issue of Harvard Men’s Health Watch suggests it might be wise to reconsider the regular use of aspirin for what it calls “primary prevention” of cardiovascular disease—that is, taking it an aspirin once a day when you don’t have heart disease but hope to prevent it.

Millions of Americans take a daily aspirin not for headaches but to hedge their heart health bets. They leave themselves at risk, according to Health Watch, for bleeding in the upper gastrointestinal (GI) region -- i.e., stomach and esophagus -- and the brain.

When blood vessels are constricted or obstructed, blood flow is reduced. Blocked arteries can cause heart attacks and strokes, so some people take aspirin because it suppresses the ability of blood to clot by making platelets less "sticky." The same trait raises the risk for bleeding in the gut and brain. “The critical question,” Health Watch says, “is whether your risk of cardiovascular disease outweighs the risk of bleeding. Right now, the answer is not simple.”

See our blog from last year about the danger of taking aspirin along with other pain relievers.

The risks are not the same for someone taking low-dose aspirin for “secondary prevention,” or those who have had a heart attack, certain kinds of stork or other cardiovascular disease. They have a high risk of additional problems, so the question of balance is clear: Aspirin is their friend (unless they are allergic to it or have a major bleeding issue).

Out of 10,000 people with a heart problem history, aspirin can prevent 250 cardiovascular events (heart attacks, strokes and sudden death). That same group will experience 40 cases of serious bleeding. For every six people helped, one will be harmed. “That's little consolation if you're sent to the hospital with internal bleeding,” Health Watch says, “but as a public health policy this risk equation is acceptable.”

Is it acceptable for you? Probably not if you’re taking it to prevent a heart “event.”

On average, for every 10,000 people taking low-dose aspirin, seven people will be helped (mostly by preventing heart attacks) and four will be harmed. Individual risk, of course, varies depending on your health profile and lifestyle choices. The benefit of aspirin rises with age, being overweight, smoking and having high cholesterol. The risk of bleeding also rises with age, but so does the risk of heart attacks and strokes, and, therefore, the potential benefit of taking aspirin.

A study in the Journal of the American Medical Association (JAMA) added fuel to the prophylactic aspirin fire. Analyzing health records in the Italian National Health Service, researchers concluded that the study “demonstrated that the incidence of major bleeding events is much higher than that recorded in randomized, prospective clinical trials. …[W]e found a 5-time higher incidence of major bleeding leading to hospitalization among both aspirin users and those without aspirin use.”

That study involved a wide range of patients; Health Watch says some probably would have had a higher risk of bleeding than the previous trial patients, which could explain the higher incidence of bleeding. That study also didn’t define the benefits of aspirin, which could have been significant.

For now, the science remains uncertain and experts disagree about who should take aspirin to prevent a first heart attack or stroke. European cardiology guidelines don’t recommend aspirin for primary prevention. In the U.S., the FDA has not approved aspirin labels touting cardiovascular disease prevention.

That could change if better primary prevention trial results indicate they should. But unless and until that happens, what should you do? The advice from the Harvard Men’s Health Watch is sensible: First, know your medical history and health profile. In other words, know as much as you can about your risk for developing heart problems. You can’t weigh potential harm against potential benefit without this information. And if you already take low-dose aspirin to head off cardiovascular disease, discuss the wisdom of this practice with your doctor.

NOTE TO READERS: The Harvard Men’s Health Watch newsletter was the major source for this piece.

Drugs known as bisphosphonates are huge sellers in the U.S., prescribed mostly for post-menopausal women to protect against bone fractures. The risk of osteoporosis (bone density loss) increases after menopause.

But the possible side effects of bisphosphonates have long been of concern if they’re taken for an extended period. Bisphosphonates have a long half-life, which means they can remain active in the body for years, and over time, users might experience cumulative damage.

In its column “Ask the Pharmacist,” Consumer Reports has renewed concern about bisphosphonates (Fosamax, Boniva, Actonel), and advises women with low bone density not severe enough to qualify as osteoporosis to forgo them. The benefits, CR says, do not appear to outweigh the risk sudden femur fractures and decay of the jaw bone.

We wrote about bone-building drugs a couple of years ago in the wake of lawsuits over the death of jaw bone tissue associated with the use of Fosamax, the most well-known bisphosphonate. Sometimes this adverse event requires surgery to remove parts of the jaw.

Another risk of this class of drugs is sudden femur (thigh bone) fractures that can happen during activity as simple as taking a step. Other unpleasant side effects include gastrointestinal ulcers, eye inflammation and incapacitating muscle, bone and joint pain.

Even the diagnosis of osteopenia—lowered bone mineral density that’s often a precursor to osteoporosis—does not warrant taking these drugs. CR supports its stance with recent analysis from the federal Agency for Healthcare Research and Quality (AHRQ).

In 2010, the FDA required Merck, the manufacturer of Fosamax, to issue new warnings about the risk of femur fractures. In June, as noted on AboutLawsuits.com, the FDA released new guidelines for taking bisphosphonates. They indicated that even people with osteoporosis should limit their exposure to bisphosphonates. The feds recommended, per an FDA report from 2011, that use be limited from three to five years, at least until more definitive data become available.

The 2011 report, according to AboutLawsuits, was issued before an FDA advisory committee was convened to review the risks associated with the long-term use of the medications. The panel favored stronger bone-fracture warning labels but did not finalize length-of-use recommendations.

Merck still faces hundreds of Fosamax fracture lawsuits.

To reduce your likelihood of brittle bones, according to Consumer Reports:

• Eat calcium-rich foods such as green leafy vegetables, low-fat dairy products, shellfish, canned sardines and salmon, and take supplements as directed by your doctor to ensure you're getting at least 1,200 milligrams of calcium per day.


• Check your vitamin D blood level. It should be greater than 30 nanograms per milliliter; supplement your diet as directed by your doctor.


• Spend 30 minutes or more each day doing weight-bearing exercises such as walking and weightlifting to support bones and increase muscle strength.


• Do a safety check of your home, which is where most falls occur.


• Learn tai chi or similar exercises to improve balance, and use a cane if necessary.


• Limit alcohol consumption and sleeping pills.

Online commerce is convenient, quick and often cost-conscious. When it comes to purchasing prescription medicine online, however, the market is fraught with risk.

Late last month the FDA initiated a public education program to inform consumers about fake pharmacies and the dangers they present. Called BeSafeRx:Know Your Online Pharmacy, the website helps people vet possible online drug sources and understand how to spot the bogus players.

Just last week, as reported by Reuters, the FDA cracked down on more than 4,100 Internet pharmacies, bringing civil and criminal charges, removing offending websites and seizing drugs worldwide. More than 18,000 illegal pharmacy websites were shut down, and $10.5 million worth of drugs were seized.

Among the unapproved and potentially dangerous medicines in last week's action were Tamiflu, Viagra and Domperidone. The latter was removed from the U.S. market in 1998 because it may cause serious adverse side effects. The feds also confiscated Isotretinoin, previously marketed as Accutane in the U.S. It was prescribed to treat severe acne but carries serious risks including birth defects.

According to an FDA survey, 1 in 4 Internet consumers has purchased prescription medicine online. Three in 10 survey respondents said they lacked confidence about how to make safe online purchases. And with good reason: The National Association of Boards of Pharmacy reported that fewer than 3 in 100 online pharmacies meet state and federal laws.

In a news release announcing the BeSafeRx program, FDA Commissioner Margaret Hamburg said:

“Buying medicines from rogue online pharmacies can be risky because they may sell fake, expired, contaminated, not approved by FDA or otherwise unsafe products that are dangerous to patients. Fraudulent and illegal online pharmacies often offer deeply discounted products. If the low prices seem too good to be true, they probably are.”

Earlier this year, we wrote about counterfeit Adderall that was being sold over the Internet. (And last week we cautioned patients about another medication risk: unregulated compounding pharmacies, one of whose contaminated compounds led to a national outbreak of meningitis.)

It can be difficult to separate the legitimate from the scammers. Fraudulent online pharmacies use sophisticated marketing techniques or phony web storefronts to appear legitimate. And even if they do supply actual medicine, there’s a high probability that the products contain the wrong ingredients, have too little or too much of the active ingredient, have expired and/or are contaminated.

As noted on AboutLawsuits.com, even slight differences in how a drug is compounded can have a big effect on its effectiveness or side effects. Also, drugs purchased from rogue online pharmacies may arrive without medication guides, warnings about potentially dangerous drug combinations or other information about side effects, all of which is supposed to be provided to consumers.

Add to that the possibility for identification theft. Fake pharmacy websites can harvest valuable personal information, such as Social Security numbers, credit card and banking information they can use for fraudulent purposes, including selling it to other criminals. Doing commerce with these websites also invites email spam and harassing phone calls.

The feds say you should buy prescription medicine online only through pharmacies that:

• require a valid prescription from a doctor or other health-care professional;


• are located in the United States;


• have a licensed pharmacist available for consultation; and


• are licensed by your state’s board of pharmacy.

1. If your report involves a life-threatening situation due to an FDA-regulated product you purchased from a website, call (866) 300-4374 or (301) 796-8240 immediately. Also, contact your doctor for medical advice.

2. If your report involves a serious reaction or problem with an FDA-regulated product, fill out an FDA MedWatch form and contact your doctor.

3. If your problem does not involve a life-threatening or otherwise serious reaction, fill out this form. To report e-mails promoting medical products that you think might be illegal, forward the email to webcomplaints@ora.fda.gov.

The death and disability toll from the contaminated spinal pain relief drugs "compounded" by a New England pharmacy continues to mount. Patients have come down with serious infections in Maryland, Virginia and eight other states, according to the Centers for Disease Control. Check this CDC web page for updates and good advice on what patients should do if they feel any unusual symptoms after a spinal injection.

Patients who are looking into possible legal action against the pharmacy should make sure that the clinic where they got the injection keeps all records of who sold drugs to the clinic.

The ongoing outbreak of spinal infections -- with so far five patients dead and 30 with serious meningitis infections in six states, including Maryland and Virginia -- shows the antiquated regulatory system for drugs that are compounded by a pharmacy.

All the injected steroid drugs that have sickened and killed patients came from a pharmacy in Massachusetts that was "compounding" the drugs: in other words, mixing different drugs together and essentially manufacturing a new drug. The drugs were contaminated with a common fungus known as aspergillus. When injected into patients' spines for chronic pain, the patients got a fungal infection of the meninges, the lining of the spinal cord and brain.

The Food and Drug Administration closely regulates the manufacture of drugs by regular manufacturers. But the pharmacies that essentially manufacture drugs are in a regulatory shadowland. They are allowed to engage in the ancient art of "compounding" on the theory that they are making customized products for individual patients. But some have enough volume, like the pharmacy in Massachusetts that sold its contaminated injection drug across the entire eastern U.S., that they really should be treated as any other manufacturer.

The New York Times has a good story explaining this regulatory gap that endangers patients who unknowingly receive these compounded drugs.

The gatekeepers are the pain management doctors and pain clinics that order these drugs. I have spoken with pain management specialists who tell me they would never dream of buying drugs from any except an established manufacturer. But big clinics and hospitals can sometimes save money by buying from the compounding pharmacies. And patients never know what they're getting.

It's a scary proposition that needs new oversight from drug safety agencies. In the meantime, if you're a chronic pain patient who gets these injections, ask your doctor what source he is using.

Check our website for an article on other ways that patients can get infections in hospitals and clinics, which has links to prevention techniques.

Anyone who’s ever had an owie after cleaning out the garage or trying to match Paul Ryan’s P90X regimen is probably familiar with names like Bengay, Flexall and Icy Hot. They are topical analgesics you apply to sore, complaining muscles and joints.

As of last month, the FDA has issued a warning about such creams, gels or skin patches because some people have reported burning pain and blistering ranging from mild to severe. Some injuries have required medical attention.

In some cases, the FDA reports, these over-the-counter (OTC) treatments caused first- to third-degree chemical burns after only one application. Symptoms appeared within 24 hours, and some people had complications serious enough to be hospitalized.

There have been 43 reported cases of burns associated with the use of OTC topical muscle and joint pain relievers containing the active ingredients menthol, methyl salicylate and capsaicin. They came to light through the FDA's adverse event reporting database and the medical literature.

Millions of people use these products, so the number of reported adverse events represents a tiny fraction of consumers. But, "There's no way to predict who will have this kind of reaction to a topical pain reliever for muscles and joints," said Dr. Jane Filie of the FDA's Division of Nonprescription Regulation Development.

Menthol, methyl salicylate and capsaicin create sensations of local warmth or coolness when applied directly to the skin, but they should not burn. Most of the severe cases occurred with products containing menthol or a menthol/methyl salicylate combination. Most involved concentrations of menthol and methyl salicylate greater than 3 percent and 10 percent, respectively. Few burn cases involved capsaicin.

If you are using an OTC topical analgesic for the first time, choose one that isn’t a combination product and one with lower concentrations of active ingredients. If your pain persists, and you have tolerated those compounds, graduate to a more powerful treatment.

Otherwise, the FDA advises:

• Don't apply these products onto damaged or irritated skin.


• Don't apply bandages to the area where you've applied a topical muscle and joint pain reliever.


• Don't apply heat to the area (heating pads, hot water bottles, lamps). Doing so increases the risk of serious burns.


• Keep these products away from eyes and mucous membranes (such as the skin inside your nose, mouth or genitals).


• If, instead of a warming or cooling sensation, you feel pain where you’ve applied the product, if it looks blistered or burned, stop using the product and seek medical attention.

Generally, when a prescription drug becomes available over the counter (OTC), it’s a good thing—it’s less expensive and available more quickly. But as a recent report on MedPage Today explains, often, something gets lost in the translation from Rx to OTC. And that loss has the real potential to harm patients.

Advertising for the newly prescription-free drug is much less likely to warn about potential risks, according to research published in the Journal of the American Medical Association (JAMA).

In the study, 7 in 10 ads for four prescription medications explained the drugs’ potential harms; only 11 in 100 ads for the same four drugs did so once they became available without a prescription.

As the study authors wrote, "Pharmaceuticals do not lose their capacity for harm after moving from behind the pharmacist's counter to in front of it. Closer attention should be paid to how such drugs are promoted to consumers."

Regulatory oversight for prescription medicine, including advertising claims, is the responsibility of the FDA. When the same drugs move to over-the-counter status, that oversight shifts to the Federal Trade Commission (FTC). Those agencies have different standards when it comes to product promotion.

The FDA requires that ads contain a "fair balance" of risks and benefits; the FTC demands only for a "reasonable consumer" standard of truthfulness. That excuses manufacturers—and their advertising copywriters—from explicitly describing both harms and benefits. So guess what? The promo balance tilts noticeably to the benefits side of things.

The researchers studied all print and broadcast ads from four commonly used drugs that moved from prescription to OTC status: the antihistamine loratadine (Claritin); the gastroesophageal reflux medicine omeprazole (Prilosec); the weight-loss medicine orlistat (Alli); and the antihistamine cetirizine (Zyrtec).

They analyzed advertising that ran two years before and six months after the drugs achieved OTC status. Once they were available over the counter, nearly 100 percent of the ads described the drugs’ benefits, versus slightly more than 8 in 10 when they available only by prescription.

So the gap in mentioning potential harms—from 7 in 10 prescription drugs to 11 in 100 OTC—was huge. Except for print ads for orlistat, the researchers said, no OTC ads mentioned contraindications or adverse effects.

And if someone wanted to research drug effects, his or her ability to get complete information is complicated by the fact that the OTC drug information was less likely to mention the generic names. As the researchers wrote, those are "key tools for consumers seeking independent information on risks, benefits, and costs."

The small sample of only four products might not represent how all prescription-to-OTC drugs are described in their promotional efforts. The researchers note that even the FDA’s direct-to-consumer advertising regulations "do not necessarily result in balanced presentations of
risks and benefits, and these guidelines are known to be inconsistently enforced."

Couple that with the less-information-is-more-sales behavior of Big Pharma, and the researchers conclude that patients get "even less information for making an informed decision, at a time when [they] must have more knowledge of whether their medications' potential benefits are worth their risks and costs."

To learn more about the risks of drug treatment, whether by prescription or over-the-counter medicine, see our backgrounder about medication errors.

One of the strongest risks for heart attack and stroke is hypertension, or high blood pressure, which is a measure of how hard the heart is working to pump blood.

The medical establishment has been aggressive in addressing hypertension with prescription drugs. But a new study in BMJ (British Medical Journal) concludes that treating patients with stage 1, or mild, hypertension with drugs has no benefit.

Study results indicated that drug treatment did not reduce total mortality risk, coronary heart disease or stroke.

Blood pressure (BP) is read via two numbers, systolic (top number) and diastolic (bottom number. Systolic reflects the maximum pressure exerted as the heart contracts, and diastolic reflects the heart at rest, or the time elapsed between beats.

BP readings generally are defined by four levels:

• normal (below 120/80);


• prehypertension (120-139/80-89);


• stage 1 hypertension (140-159/90-99);


• stage 2 hypertension (160+/100+).

The BMJ study results were drawn from controlled, randomized trials of more than 8,900 patients with stage 1 hypertension. They were treated for four to five years. People with pre-existing cardiovascular disease were excluded.

Drugs prescribed to treat hypertension fall into several categories, including diuretics (Lasix, Bumex, etc.), ACE inhibitors (Vasotek, Prinivil, Mavik, etc.), beta blockers (Lopressor, Levatol, Inderol, etc.) and others.

Side effects of blood pressure drugs can be significant. They vary depending on the class of drug taken, and include:

• irregular or rapid heartbeat;


• erectile dysfunction;


• dizziness;


• headaches;


• weakness, fatigue;


• leg cramps;


• intense, sudden foot pain;


• depression;


• insomnia;


• dry cough;


• skin rash;


• loss of sense of taste;


• constipation;


• swollen ankles;


• dry mouth;


• diarrhea;


• heartburn;


• fluid retention;


• joint pain.

Dr. Julian Tudor Hart responded to the research with particular insight. “Why has it taken more than 30 years to reach this conclusion,” he wrote, “when it was already evident from any careful and critical reading of the trials claimed originally to justify interventions in the diastolic range 90-100 mm Hg? And what should we do now to get practice onto a more rational footing?”

Hart has long believed that controlling blood pressure with what he calls a “whole community,” or less pharmaceutical, approach is possible and effective. But the medical establishment had been steadfast in finding the 90 mm Hg (millimeters of mercury, the silver element visible in the BP gauge) as the threshold for drug intervention.

After a series of symposia on mild hypertension sponsored by the World Health Organization decades ago, Hart refused to support this advice. The WHO organizer, he writes, “appealed to me to do what all other participants had done, and sign the statement, reminding me that three transnational pharmaceutical companies were sponsoring all three symposia and had a right to expect results. I still refused.”

Really, is anyone surprised that Big Pharma is happy when the medical establishment opts for scorched-earth treatment when a drug-free approach might work better?

After a nasty, profane exchange with other medical professionals, Hart relented and signed the statement supporting drug intervention for mild hypertension. “I thought I had reached the limit of what a mere GP could do without becoming hopelessly isolated,” he explains, but, “… I was never convinced that the very small reductions in cardiovascular and cerebrovascular event rates justified the conclusion, except in diabetics.”

Another researcher at the symposium told of the pressure he had felt to find positive results in large scale studies or risk losing funding for future research. That man, Hart, says, “concluded that, realistically, medical scientists might have to accept that some degree of ‘quasi-science’ was inevitable and therefore justifiable, for obtaining necessary state funding. Conclusions must sometimes be bent to our market.”

Science, Hart admonishes, “cannot include a market for medication accepting all the plausible mythologies lobbyists can maintain among the lay public, media editors and politicians.” The body of knowledge is advanced not only “by showing that new methods are useful, but equally by showing that they are no better than old methods, or perhaps don't work at all. All three outcomes represent worthwhile gains in knowledge.”

Although not all causes of high blood pressure are known, several factors contribute, many of which individuals can address without drugs:

• smoking;


• being overweight or obese;


• lack of physical activity;


• too much salt in the diet;


• excessive alcohol consumption;


• stress;


• advancing age;


• genetics;


• family history of high blood pressure;


• chronic kidney disease;


• adrenal and thyroid disorders.

If your hypertension is mild, and you do not have other, complicating disorders (diabetes, kidney disease, etc.), do not accept a prescription for blood-pressure medicine without discussing lifestyle changes first. If your doctor is unwilling to have this conversation, or to see beyond the pill fix, it’s time for a second opinion.

Just as children require medical treatment different from that of adults, seniors have specific health-care needs as well. As we’ve noted, elderly patients are more sensitive to some drugs, less to others, can present different symptoms of common conditions and often communicate differently from younger people.

They are also disproportionately large consumers of medication. A recent study published in PLoS One puts that reality into an uncomfortable context by concluding that inappropriate drug prescribing is common for elderly patients.

The risk, the researchers said, is about 1 in 5 prescriptions. The most common inappropriately prescribed drugs are:

• propoxyphene (Darvon and other narcotic pain relievers);


• doxazosin (alpha blockers to treat high blood pressure and other disorders);


• diphenhydramine (Benadryl and other antihistamines); and


• amitriptyline (Elavil and other antidepressants).

As reported on MedPage Today.com, the median rate of inappropriate prescriptions was 1 in 5, but the high end of the range was nearly 4 in 10. The authors wrote:

"Despite intensified efforts to scrutinize and improve the quality of medication prescription among elderly persons in the primary care setting, inappropriate medication prescriptions are still common."

More than 1 in 3 at-risk older individuals experience drug-related adverse events, even in cases where less hazardous options are available, they noted.

The researchers reviewed 19 studies to assess the use by older patients of several classes of drugs including analgesics (pain relievers), hypnotics (sleep inducers), antihypertensives (for high blood pressure) and anticholinergics (for spastic and other disorders).

Some lower-risk drugs were more commonly prescribed than higher-risk drugs in the same category. For example, propoxyphene, which is classified as low risk, was the most common inappropriate medication, but higher risk drugs in the same class, such as Demerol, were the least commonly prescribed. Doxazosin, a low-risk drug, was the most common inappropriate antihypertensive prescribed, and guanethidine, a high-risk drug, was the least prescribed. Digoxin, which treats abnormal heart rhythms, was the most commonly used inappropriate medication, and disopyramide, a high-risk antiarrhythmic, was the least common.

But some high-risk drugs were commonly prescribed inappropriately. The high-risk anticholinergic diphenhydramine was most often used. (The least common in this class were belladonna alkaloids, which also are high risk.) The same was true for amitriptyline (most common) and doxepin (least common)—both are considered high risk. Ditto for muscle relaxants—cyclobenzaprine (Flexeril and others) was the most common, and metaxalone (Skelaxin) the least. Both are high risk.

All sedative hypnotics are considered high risk. In this class, diazepam (Valium) was the most used, and alprazolam (Xanax) and oxazepam (Serax) had the lowest rates.

Acknowledging that individuals respond differently to drugs within a given class, the researchers advise doctors generally to avoid the riskiest agents, and to monitor patients closely. They advocate a “decision support system” to alert doctors of potential side effects and interactions when they write prescriptions.

Surely we are not alone in thinking this is simply part of a doctor’s job—when you prescribe medicine to a patient, you must know, based on age, gender and full medical history—how it’s likely or even possible to affect that person, in ways both good and harmful.

When a doctor prescribes medication, always ask:

What is this medication for?
What will happen if I don’t take this medication?
When can I expect this medication to work for me?
What do I do if I have a problem with this medication?
Can I take this medication with all my other medications?

For more information, see my backgrounder about medication errors. To report an adverse event from taking a drug, call the FDA’s MedWatch program at (800) 332-1088 or file a report online.

How medicine gets into your body is called a “delivery system.” It might be an injection, a pill, a drink or a piece of adhesive you stick to your skin. The latter is a “transdermal patch,” and it might be the preferred method to absorb medication if you have trouble swallowing pills, trouble remembering to take medicine on schedule or the medication is most effective if it’s absorbed slowly and regularly.

As simple as a patch is, it’s actually a sophisticated drug delivery system designed to release small quantities of the drug through the skin and into the bloodstream over a long period of time. Some patches are worn for weeks at a time.

Medications commonly delivered via patch include:

• pain relievers;


• nicotine (for people trying to quit smoking);


• hormones;


• drugs to prevent angina (chest pain caused by insufficient blood to the heart);


• drugs to treat motion sickness.

The diclofenac (Flector) patch relieves minor pain when placed directly over a bruise or sprain (other patches are placed in specific places noted on the product’s directions). Some prescription patches—fentanyl (Duragesic)—deliver a strong narcotic, and are used only to treat chronic, severe pain.

The idea behind the nicotine patch is to wean smokers off their dependence slowly and reduce withdrawal symptoms. Nicotine patches (Habitrol, Nicoderm, Nicoderm CQ and Nicotrol as well as generics) are available in various strengths, and the idea is to decrease the strength as time goes by.

Hormone patches often are prescribed to relieve symptoms of menopause and prevent osteoporosis (bone loss), and low testosterone for men.

Nitroglycerin patches (Minitran, Nitro-Dur, Nitrodisc and Transderm-Nitro) address angina by relaxing the constricted blood vessels of coronary artery disease (CAD) to enable the heart to get more blood and oxygen. Nitroglycerin patches can prevent the pain of angina but do not treat chest pain.

The obvious benefits of transdermal patches, noted above, are accompanied, like all medicine, by potential risks and side effects. If your doctor prescribes or suggests a drug patch for you, ask:

• What are the expected side effects?


• What are the possible side effects?


• What other drugs should I avoid?


• What food or liquids should I avoid?


• Are there environmental effects (for example, should you avoid sun exposure)?


• For what side effects should I call you (for example, fever or rash)?


• How long will the drug be active after I remove the patch?

• Apply the patch firmly; it might take 20 or 30 seconds to get all of the adhesive stuck firmly in place.


• Wash your hands after applying a patch to yourself or someone else.


• Use only one patch at a time unless the instructions say otherwise.


• Patches might have to be removed if you need an MRI during the course of treatment; ask your doctor or X-ray technician.


• If you develop skin irritation from the adhesive, replace the next patch in another area. If the problem remains, call your doctor.


• When your remove a skin patch, fold it to stick the adhesive edges together. Dispose of it out of reach of children or pets.


• Gently wash the area with soap and water.

Overdose can also happen if the user lets the area of the patch get hot, such as with an electric blanket.

Beware of the risk of overdose to children if:

• they find patches and put them in their mouths (the Poison Control Center reported one child who had several fentanyl patches stuck to the roof of her mouth);


• they get adult patches stuck to their skin after rolling in the parental bed where a patch has come unstuck from its original host.

Call the poison center even if the person seems OK—even after removing the patch, some drug remains in the body. The poison center will stay in touch with you to be sure that no problems develop.

We’ve discussed the fact that despite the population’s increasing resistance to antibiotics—and therefore their diminishing ability to beat infection—pharmaceutical companies aren’t exactly eager to develop new antibiotics because there’s little profit in it.

But antibiotics aren’t the only class of drugs lagging in development. As described on MedPage Today, innovative drug development lags, according to two researchers, because the pharmaceutical industry prefers to invest in protecting the franchises it has built around existing products.

Resources devoted to finding new products for unmet needs are paltry compared with what Big Pharma spends on marketing and on research to refine its current drugs, claim Donald W. Light of the University of Medicine and Dentistry of New Jersey in Cherry Hill, N.J., and Joel R. Lexchin of York University in Toronto.

"This is the real innovation crisis: Pharmaceutical research and development turns out mostly minor variations on existing drugs, and most new drugs are not superior on clinical measures," they wrote in an article published in BMJ, the British Medical Journal.

Reasons given for failing to invest in drug development are cost (developing and bringing drugs to market averages $1.3 billion per each approved new chemical entity, or NCE), and a decline since the mid-1990s in the rate of NCE approvals.

Light and Lexchin, however, find these arguments mostly bogus, and founded on phony statistics.

"Both claims serve to justify greater government support and protections from generic competition, such as longer data exclusivity [restricting competition from generic versions] and more taxpayer subsidies," they wrote.

The $1.3 billion figure is inflated, the researchers claim: "[H]alf ... comes from estimating how much profit would have been made if the money had been invested in an index fund of pharmaceutical companies that increased in value 11 percent a year, compounded over 15 years," a conclusion they reached as the result of research at Tufts University.

Half of the remaining Big Pharma balance is paid, Light and Lexchin say, by taxpayers in the form of deductions and credits. The companies' actual average expenditure, they calculate, is only about $330 million, and that’s for the most expensive new products, which constitute about 2 in 10 drugs.

The average expenditure for all NCEs is about $90 million.

The decline in NCE approvals is an exaggerated claim Light and Lexchin contend. The mid-1990s benchmark is misleading because that’s when there was a large spike in approvals associated with the introduction of FDA "user fees" that allowed the agency to clear a backlog of new drug applications.

Recent annual rates of 15 to 25 NCE approvals are consistent with averages from 1955 into the early 1990s, Light and Lexchin say.

The percentage of approvals for true medical advances, versus copycat products, hasn’t declined very much. Thirty-four percent of drugs approved from 1974 to 1989, Light and Lexchin report, represented "important therapeutic gains."

The real enemy of innovation, they suggested, is the industry's lust for marketing and for protecting existing blockbuster products. An article in PLoS Medicine a few years ago showed that for every dollar of revenue pharmaceutical companies spend on discovering NCEs, they spend almost $25 on promotion.

Pharmaceutical company behavior, Light and Lexchin say, exploits patent protection laws and free-market competition by keeping potential competitors with generic versions out of the market.

They propose that regulatory agencies such as the FDA make requirements for new drug approvals considerably more rigorous. Simply being somewhat more effective than a placebo (fake or inert therapy) and relying on surrogate endpoints—measuring the effect of a certain treatment by correlating it with but not proving a clinical endpoint—instead of stringent clinical results are insufficient. Such low standards, they say, “allow approval of medicines that may even be less effective or less safe than existing ones."

Light and Lexchin also believe that high prices for new products are not an appropriate reward for drug innovation. They support giving large, taxpayer-funded cash prizes to companies that deliver demonstrable improvements in health care, and allowing immediate generic competition as a cost-control measure.

That way, they say, "innovators are rewarded quickly to innovate again," health-care costs are reduced and patient health and quality of life improve.

Our August newsletter about dietary supplements included some cautionary advice about some so-called “natural” supplements that can cause significant harm. One was Reumofan, a product manufactured in Mexico and marketed as a remedy for pain.

The FDA had issued a warning earlier this year about it after receiving several adverse event reports, including stroke, gastrointestinal bleeding, liver problems and worsening glucose control.

Last week, the feds raised the volume of concern about Reumofan after additional reports of bleeding, strokes and even death, according to AboutLawsuits.com.

The warning, “FDA issues new safety alert on Reumofan Plus and Reumofan Plus Premium,” says that these products contain drugs that are not declared on the labels. They’re also illicit.

The worrisome active ingredients are dexamethasone, diclofenac, and methocarbamol, a combination whose risk factors include severe injury or death, according to the regulators. Dexamethasone, a corticosteroid, is so powerful that the FDA advises people taking Reumofan products to consult their doctor before they stop using it. It must be discontinued under medical supervision because of a risk of withdrawal syndrome.

Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID); methocarbamol is a muscle relaxant. The former can increase the risk of heart attack, stroke and gastrointestinal problems, and the latter can cause dizziness, low blood pressure and compromised mental and physical activity.

It is illegal for products billed as dietary supplements, which are not subject to the same regulatory scrutiny as drugs, to contain FDA-controlled medications.

If you use or recently used any Reumofan product, contact your doctor immediately. If you had a problem after taking Reumofan, contact MedWatch, the FDA’s adverse event reporting program, at (800) 332-1088 or online here.

Like reviews of restaurants and plumbers, these days doctors can be rated six Internet ways from Sunday. Some sites are fair, useful and worth your time; some provide more opportunities to vent than to advise. We looked at the doc-rating phenomenon in “The Ups and Downs of Patient Ratings of Doctors.”

When it comes to medical provider reviews, there’s an undeniable cred-boost if the info provider is a member of the class under scrutiny. Writing on KevinMd.com, Dr. Jennifer Gunter, who practices obstetrics and gynecology, offers guidance on how to rate your ob/gyn and, if he or she is found wanting, to find a better provider.

In general, she looks for communication skills: “how a doctor discusses options if the care seems valid or if a second option is in order,” and the ability to explain a treatment plan as it relates to recommended guidelines. She also looks for board certification.

When patients come to her with tales of medical misadventure, sometimes, she writes, “they make me want to shout, ‘Your doctor did/said what?!’ These are red flags, because not only are these recommendations potentially harmful, but if your doctor recommends one thing that is so flagrantly bad, well, uh, um, how can you trust the rest of their care?”

Precisely. So here are her six red flags that should prompt you to seek ob/gyn care from someone else.

1. Giving you a prescription for estrogen-containing birth control (pills, patch or ring) without inquiring about migraines. Migraines with aura are an absolute contraindication to estrogen-containing birth control because of an increased risk of stroke. A doctor’s failure to inquire about migraines indicates unfamiliarity with guidelines from the Centers for Disease Control and Prevention (CDC).

2. Blaming pelvic pain on pelvic organ prolapse. Prolapse is not a cause of pelvic pain. It causes a bulge and a feeling that something is coming out of the vagina, but it does not cause pain. A doctor who thinks the two are related knows nothing about prolapse and even less about pain. Or just wants to operate.

3. Booking you for incontinence surgery without a bladder diary (a log that measures input and outgo for 48 hours) and a post-void residual (a test to ensure you empty your bladder correctly). This simple diary and test can distinguish people who can (and can’t) be helped by surgery, as well as indicate some people who could be even worse after surgery.

4. Dismissing your concerns about pain with sex. Painful sex, called dyspareunia, is not normal: Sex should not hurt. If it does, taking a complete history and conducting an appropriate exam are in order. Many medical conditions can cause painful intercourse and not one of them is “It’s all in your head.”

5. Giving you a prescription for fluconazole (Diflucan) if you also take a statin drug for high cholesterol. These two medications can interact with fatal results and should not be given together, especially for a routine yeast infection.

6. Blaming pelvic pain on pressure from fibroids. Fibroids are benign tumors of the uterine muscle that can cause irregular or heavy bleeding, but they do not cause chronic pain. Sometimes, when they outgrow their blood supply, they degenerate into an acutely painful condition, but that can be diagnosed with imaging studies, and is not chronic pain. A large fibroid uterus would weigh 1 pound, so if a 1-pound uterine resident caused severe daily pain, how could pregnancy ever be endured?

Until last week, you didn’t hear much anymore about gonorrhea, a sexually transmitted infection formerly known as a “venereal disease.” It’s back in the limelight because the news is all bad. The Centers for Disease Control and Prevention says that gonorrhea is getting dangerously close to being untreatable.

The problem, as outlined by NPR, is that antibiotic options to treat gonorrhea are becoming increasingly limited. Basically, there’s only one antibiotic that can still eradicate the infection.

We’ve written before about the health threats of antibiotic resistance.

About 700,000 Americans get gonorrhea every year. If it’s left untreated, the infection can cause infertility and life-threatening ectopic pregnancies.

"Gonorrhea used to be susceptible to penicillin, ampicillin, tetracycline and doxycycline — very commonly used drugs," Jonathan Zenilman, who studies infectious diseases at Johns Hopkins, told NPR. But one by one, each of those antibiotics — and almost every new one developed since —stopped working. One reason is that the bacterium that causes gonorrhea can mutate quickly to defend itself, Zenilman said.

Another reason these drugs don’t work anymore is that they’re overprescribed and overused. That enables the bugs to “learn” how to survive against them; that is, they mutate until they become resistant. When antibiotics intended to treat gonorrhea also are used to treat urinary tract, upper respiratory and other kinds of infections, the germs are just given that much more opportunity to develop resistance. Also, when patients fail to take the full course of an antibiotic—that is, they stop taking the drug when their symptoms improve even though they’re supposed to take every pill in the prescription—bacterial resistance improves.

Doctors recently had only two antibiotics that still worked well against gonorrhea — cefixime and ceftriaxone. But last week, the CDC announced that in the U.S., gonorrhea had started to become resistant to cefixime.

"We're basically down to one drug … as the most effective treatment for gonorrhea," one federal official said.

Even worse, cefixime and ceftriaxone are in the same class of antibiotics. So it's only a matter of time before ceftriaxone loses its punch, too. "The big worry is that we potentially could have untreatable gonorrhea in the United States," the official said. It has happened in other countries.

The CDC said doctors should stop using cefixime immediately, and has issued new guidelines for treating gonorrhea.

They know it won’t be easy: Ceftriaxone is an injection, not a pill. And it should be given along with at least one other antibiotic.

Even so, “it's only a matter of time based on the history of this organism until resistance does develop," the CDC official said.

In a follow-up story, NPR discussed the scope of the antibiotic-resistance problem with Dr. Arjun Srinivasan, an epidemiologist with the CDC. He made clear that the responsibility to stop overusing these drugs lies with both patients and doctors.

“As patients,” he said, “we need to be informed consumers. We should never demand antibiotics when our doctors don't think we need them. And as medical providers, we need to consider very carefully when we are writing a prescription for an antibiotic. We need to make sure that the patient actually needs the antibiotic.

“And if they do, we need to make sure that we're up on the latest information so we're giving exactly the right drug for exactly the right dose for exactly the right time.”

Srinivasan reviewed the need for hospitals and medical staff to practice infection control.

One of the major concerns with antibiotic resistance is the drugs’ use for livestock, which we discussed earlier this year, and how it promotes resistance via the food chain. Srinivasan, as a federal official, danced around that one, and someone called him on it in the story’s website comments:

“Dr. Srinivasin conveniently dodged the question about antibiotics in food animals given as growth promoters. It's unfortunate he did so; I assume he's not up on the issue. It's huge, probably more important than medical use.”

The development of new drugs is troubled, too, because—surprise!—the profit motive isn’t there. As Srinivasin said, “It's not simple to develop new antibiotics. Another thing that you hear from drug companies is, of course, that these are drugs for which there is not a substantial profit margin. And as drug companies, they have shareholders to whom they are responsible and they have a duty to try and develop drugs that are going to make money for their shareholders.”

He suggests that this problem can be addressed through collaboration between government and Big Pharma.

Good luck with that.

A couple of recent news reports support the notion that the more we know medicine, the less we know about health. The latest yes/no/maybe answer to a health question concerns grapefruit, a fruit long known to affect how our bodies process drugs.

As reported by U.S. News & World Report, patients with incurable cancer who drank 8 ounces of grapefruit juice a day enhanced the effect of a drug they were taking. The study was reported in Clinical Cancer Research.

The drug, sirolimus (Rapamune), suppressed the immune system and is not approved for treating cancer. It’s generally prescribed to prevent rejection after a kidney transplant, and to treat psoriasis. It was included in this study because its derivatives have been used to treat kidney and breast cancer.

Some study patients responded positively to the drug/juice combo—their condition stabilized for a while. With the exception of one patient, tumors did not disappear. But the primary result of the admittedly small study (about 150 patients with incurable cancer and no effective treatment) was that grapefruit juice enabled the drug to be used in smaller doses, which would reduce side effects and possibly cost.

Sirolimus has poor “bioavailabilty”—that means the body can’t use it efficiently. Only about 14 percent of it is metabolized. Because grapefruit is known for boosting the effects of other drugs, researchers wanted to see if it could improve this one’s bioavailability. And it did.

Sirolimus costs about $1,000 a month. Combine it with drinking grapefruit juice, researchers suggest, and the cost could drop to around $300 a month. The cost of other expensive cancer drugs ($3,000-$10,000 a month) also could be slashed by equivalent amounts when taken with grapefruit juice.

Lowering the dose, of course, also could reduce side effects, which include nausea and diarrhea.

But because the effects of grapefruit vary among different drugs and dosages, broad generalizations can’t be drawn, and consumers are advised not to experiment on their own.

The research is in its infancy. Grapefruit juices vary in how well they inhibit the enzymes in the liver and intestine that break down drugs, leaving more of the drug available to be metabolized, and individual biochemistry also affects absorption.

But yang to that study’s yin was noted recently by consumer organization Public Citizen’s recent Best Pills, Worst Pills newsletter. It warned that drinking grapefruit juice while taking certain medications can be really bad medicine, a cautionary tale described by AboutLawsuits.com.

Public Citizen listed 82 medications whose effects can be altered by drinking grapefruit juice. The combination might result in some delivering too much of the drug, and others too little, the organization said. Earlier this year, the FDA reported that grapefruit juice might reduce the effectiveness of some drugs.

Among the common drugs Public Citizen identified as problematic in terms of grapefruit interaction are:

• Lipitor;


• Tegretol;


• Propulsid;


• Celexa;


• Valium;


• Benadryl;


• Multaq;


• Prozac;


• Haldol;


• Serzone;


• Viracept;


• Prilosec;


• Paxil;


• Seroquel;


• Zoloft;


• Viagra;


• Zocor; and


• Coumadin.

• Ask your pharmacist or doctor if grapefruit or grapefruit juice affects absorption of the medicine. If so, ask other juices are a safer option.


• Read the medication guide or patient information sheet that comes with your prescription medicine. Some advise not to take the drug with grapefruit juice.


• Read the drug facts label on nonprescription medicine; it often mentions grapefruit or other fruit juices that might pose a problem.


• If you must avoid grapefruit juice with your medicine, check the label on other fruit juice or drinks flavored with fruit juice to make sure they don’t contain grapefruit juice.


• Seville oranges (often used to make orange marmalade) and tangelos (a cross between tangerines and grapefruit) affect the same enzyme as grapefruit juice, so avoid them if your medicine interacts with grapefruit juice.

Three anemia drugs--Epogen, Procrit and Aranesp--have generated more than $8 billion in U.S. sales. Epogen became the single costliest medicine under Medicare, and taxpayers shell out as much as $3 billion a year for these drugs.

A growing body of research has shown that the drugs’ benefits, including quality-of-life issues such as “happiness,” are seriously overstated. Worse, according to a long story in The Washington Post, their potentially lethal side effects, including cancer and strokes, were long overlooked.

Anemia occurs when the body produces too few red blood cells, which carry oxygen from the lungs to the rest of the body. The drugs are artificial versions of a natural hormone called erythropoietin, which stimulates the body to produce red blood cells. Before the drugs’ advent, patients were given transfusions of red blood cells, a cumbersome process that can take hours.

Epogen and Procrit were approved by the FDA in 1989 for patients with kidney disease. Amgen manufactured both; Procrit was licensed by Johnson & Johnson. Amgen’s Aranesp was approved in 2001.

Last year, an 84-page Medicare research study determined that among most kidney dialysis patients, who compose the drugs’ largest market -- the kidneys are where the natural hormone is made -- there was no solid evidence that they made people feel better, improved their survival or had any “clinical benefit” except a higher red blood cell count. As The Post said, “It was a remarkable finding of futility: While drugmakers had seen billions in profits over 22 years, much of it from taxpayers, millions of patients had been subjected to dangerous doses that might have had little advantage.”

One of those patients was Jim Lenox. On the day the frail cancer patient received his last injection in 2008, he was awaiting discharge from the Baltimore Washington Medical Center. Then a nurse said he needed another dose of anemia drugs.

His wife, Sherry, wondered why, because his blood readings had been close to normal. But the Lenoxes deferred to the professionals and accepted an injection of Procrit, which his cancer clinic normally billed for $2,500 each.

Hours later, Lenox was dead.

The story behind the anemia drugs is long and complicated, and illustrates how the financial incentives that are integral to the U.S. health-care system contribute to its inefficiency and lethal potential. We wrote about this smarmy situation last year.

Drug trials conducted by both Amgen and Johnson & Johnson missed the dangers and promoted the benefits that years later would be deemed unproven. The companies took more than a decade to fulfill their research commitments. And when bureaucrats tried to curb the largest doses, Congressional lobbyists were successful, and regulators opened the spigot.

The fault of dangerous drugs being promoted on the open market is shared by doctors, clinics and hospitals, whose budgetary pressures contribute to a “more is more” philosophy. The more they treat, the more they earn, the bigger the dose, the bigger the payoff.

Unlike medications you fill at a pharmacy, drugs administered by physicians, such as the anemia group, can be profitable for them.

Big Pharma offered doctors incentives to give large doses and they offered volume discounts. Most critical, The Post says, was the lobbying pressure, under which Congress and Medicare administrators forged a system in which doctors and hospitals were reimbursed more for the drug than they paid—as much as 30 percent, according to the Medicare Payment Advisory Commission, a group that advises Congress. The markup on patients covered by private insurance was even larger.

At the peak of the drugs’ use in 2007, more than 8 in 10 Medicare dialysis patients were receiving the drug at levels higher than the FDA now considers safe, according to federal statistics. (Other patients got the drugs, but records kept on dialysis patients are better.)

“An oncologist could make anywhere from $100,000 to $300,000 a year from this alone. And all the while they were told that it was good for the patient,” Charles Bennett, from the Medication Safety and Efficacy Center of Economic Excellence at the University of South Carolina, told The Post.

During his cancer treatment, Jim Lenox was given Aranesp several times at a clinic. The insurance company reimbursed it about $900 for each, although the clinic would have paid about $600.

The profit margin for Amgen was far higher than the industry average. Much of it came from the pockets of taxpayers. A Washington University professor of medicine who had been paid by Amgen to promote the drug, called its success “a paradigm for the pharmaceutical industry.” He later turned critic after Aranesp’s dangers became known while Amgen continued to promote higher doses.

Both companies declined the paper’s requests for interviews and claimed that their primary interests were serving patient needs and providing consumer information.

The market expanded to nearly all dialysis patients, not just the estimated 16 in 100 who require blood transfusions, and the size of the average dose more than tripled. The FDA approved the drugs to treat anemia in cancer and AIDS patients, as well as those getting hip and knee surgery.

The drugmakers agreed to conduct safety studies, but the full results were never published. Amgen filed a “clinical study report” with the FDA in 1995, claiming its research commitment was fulfilled. The FDA did not deem the study completed until March 2004, almost 15 years after the company agreed to conduct it.

Another study in conjunction with the drugs’ approval was supposed to have 400 patients. Eleven years after initiating it, Johnson & Johnson said it was having difficulty recruiting enough, so statistically significant conclusions were elusive. And the FDA said significant amounts of data were missing.

With FDA approval, Johnson & Johnson halted the study in 2004. Medicare researchers later noted that patients in the trial who took the drugs appeared more likely to die than those who took a placebo, or fake, inert drug.

The drugmakers committed to doing another study, which was supposed to be completed by 2008. It still isn’t finished and Amgen doesn’t expect to finish until 2017 — nearly 25 years after the drug was approved for use in cancer patients.

Still another study funded by Amgen involved dialysis patients with a history of heart trouble. It was supposed to study the effect of the drugs in boosting certain blood levels close to normal, instead of simply higher than the anemic levels, which had been medically acceptable. That trial was stopped three years after it began because patients in the “normal” higher-dose group were dying or having heart attacks at a higher rate than those in the lower-dose, lower-level group.

What should have been a clear warning wasn’t: The FDA didn’t limit the recommended dosing levels, and the reason for the “increased mortality” at the higher doses, according to the label, “is unknown.”

In 2006, a study published in the New England Journal of Medicine reported that kidney patients taking higher doses were linked to higher risks of hospitalization, strokes and death. Some Danish researchers stopped a trial of Aranesp in cancer patients because of an increase in deaths and tumor growths.

Finally, the FDA ruled out the drugs’ use for cancer patients considered curable and for patients considered only slightly anemic. Maximum recommended doses were lowered, and the agency told doctors to use the smallest amount possible to avoid a blood transfusion. The agency removed the quality-of-life claims from the label.

Last year, nearly two decades after the Office of the Inspector General first suggested it, economic incentives to use more of the drugs on patients in dialysis were withdrawn. Medicare implemented a system under which health-care providers are allowed a certain amount of money per dialysis patient, rather than more money for each dose.

“The effects were immediate,” The Post reports, “suggesting again that health is not the only factor that doctors weigh in treating patients. After a quarterly sales plunge in April, Amgen chief operating officer and President Robert Bradway blamed the drop on the new payment scheme.”

Still, no major class-action lawsuits have been mounted, presumably at least in part because the patients taking the drugs were already ill. Amgen has been hit with whistleblower lawsuits alleging that the company engaged in illegal sales tactics.

But for people like Sherry Lenox, questions remain: Although her husband’s death certificate says he died of cancer, did he? Or was he he killed by the drugs he took to treat it?

The drug study was small, and the participants were recruited via an Internet forum of people who were hardly objective—they all had suffered adverse side effects. But despite these cautions, the research recently published in the Journal of Sexual Medicine about the hair-loss drug Propecia was significant.

As noted on AboutLawsuits.com, the FDA announced in April that Merck, the drug’s manufacturer, would update the warning label on its packaging to make clear that the sexual side effects some men experienced might continue even after they no longer used the drug.

To call impotence and depression “sexual side effects” is to minimize the reality some men live with long after they give up a drug they hoped would address their concern about going bald.

The research from George Washington University concluded that erectile dysfunction, decreased libido, genital shrinkage and fuzzy thinking could be permanent for some men who used the drug (finasteride), which blocks production of a hormone (dihydrotestosterone, or DHT) that can cause “male pattern baldness.”

Some users have become severely depressed and one man reportedly committed suicide because of the effects of Propecia.

The drug was approved by the FDA in 1997, and until recently its label said sexual side effects were temporary, and would resolve if the user stopped taking it. Merck had updated Propecia’s label several years ago in countries where it was sold other than the U.S. But, according to AboutLawsuits, the company’s U.S. information continued to maintain that the sexual problems it reported during clinical trials would resolve when the drug was discontinued. Why patients in one country would respond differently from patients in another country, of course, defies scientific explanation.

The new study examined 54 men who had been diagnosed with persistent sexual problems after taking Propecia. They were otherwise healthy, young and had no previous history of sexual dysfunction. After nine to 16 months, more than 9 in 10 reported that they still suffered side effects. They had problems no matter how long they had taken Propecia. The lead researcher concluded that most men who experience Propecia-related sexual dysfunction longer than three months after they ceased taking it can expect the symptoms to persist for months or years.

Lawsuits over the adverse effects have proliferated for Propecia; its predecessor, Proscar, is a stronger formula and generally is prescribed to treat an enlarged prostate. It, too, now bears a new warning label.

Sometimes hair loss is due to factors other than genetics, such as thyroid or autoimmune disorders, fungal infections or emotional stress. Chemotherapy treatments as well can prompt hair loss. Before you consider pharmaceutical options to address baldness, consult your doctor to determine if you have an underlying medical condition. And make sure you read the information about Propecia and other drugs such as Rogaine (minoxidil).

Last week we reported about the widely publicized criminal behavior of pharmaceutical giant GlaxoSmithKline, and the $3 billion fine it will pay for its crimes. Thanks to Kaiser Health News (KHN), consumers can get the gory details of just how Big Pharma inflates drug sales and the cost of health care.

It’s about doctors who leverage their medical celebrity into roles as drug shills. It’s about doctors who accept fancy trips and recreational pursuits from the companies who supply their wares It’s about spinning research results into fictional scenarios that make a great story and really bad patient care.

Courtesy of KHN, here are some of the players and their playgrounds with which Glaxo promoted the depression drugs Paxil and Wellbutrin and the diabetes drug Avandia.

• Glaxo paid Dr. Drew Pinsky (radio call-in show “Loveline,” reality TV show “Celebrity Rehab with Dr. Drew”) $275,000 to promote Wellbutrin “in settings where it did not appear that Dr. Pinsky was speaking for” Glaxo.


• On a radio show Pinsky said the active substance in Wellbutrin “could explain a woman suddenly having 60 orgasms in one night” even though Wellbutrin was approved to treat only major depression.


• Glaxo promoted Wellbutrin “knowing that much of the cost of the unapproved, nonmedically accepted and/or inappropriate uses would be borne by federal health care programs.”


• In 2000 and 2001, Glaxo flew psychiatrists to resorts (El Conquistador in Puerto Rico and Renaissance Esmeralda in Palm Springs, Calif.) to promote Paxil for children, even though it was unapproved for that use. “Results suggest that the Paxil Forum had a significant impact on Paxil market share in the months after attendance,” according to a Glaxo memo.


• Glaxo paid what prosecutors described as kickbacks to doctors in the form of consulting fees, entertainment, travel and “sham advisory boards.” It tracked their prescribing habits. A Glaxo memo emphasized that only “KEY Customers” (high-prescribing doctors) should get free tickets to Boston Bruins and Celtics games.


• “When I asked for the business he laughed,” one Glaxo sales rep said of a doctor whom he had treated to a St. Louis Cardinals baseball game. “I didn’t really see the humor in it. How could he think I wouldn’t ask for the business when I’ve treated his family to a day at the ball park.”

So if you’re going to accept gifts, people should know about it. The 2010 health-care reform legislation supports that notion, and as of next year, the Physician Payment Sunshine Act will require doctors to disclose such activity.

In the meantime, you can look up any number of palm-crossing transactions between doctors/researchers and the medical drug and device industry on the “Dollars for Doctors” page of ProPublica, a nonprofit investigative news operation.

Should anyone doubt that these professional courtesies have the potential to affect someone’s health adversely, consider this comment posted at the end of the KHN story earlier this month:

“I’m on a brand medicine that has a generic. The brand drug is at least ten times the cost of the generic. I have asked my doctor to switch me to the generic and he refuses. He always says to me, ‘I’m the doctor. If you don’t like how I do things, there’s the door.’ The trouble with making my exit is that I’m not sure I can find another doctor that takes Medicare and I’m sure my current doctor will put me on the black list. He’s done to his other patients and I’m sure he’ll do it to me.”

Early this year the Centers for Disease Control and Prevention issued a report quantifying the epidemic of drug overdoses and adverse events from the use of opioids, otherwise known as narcotics. The report, “Grand Rounds: Prescription Drug Overdoses — a U.S. Epidemic,” pointed out that too many doctors prescribe powerful painkillers such as OxyContin without completely understanding the complexity of alleviating chronic pain and without having the necessary information about the risks and often exaggerated benefits of narcotics.

So a lot of interested parties looked forward to last week, when the FDA issued guidelines for prescribing the dangerous drugs. A lot of interested parties were disappointed.

Known as the risk evaluation and mitigation strategy (REMS), the process requires 20 drug manufacturers to sponsor physician education programs about how to prescribe their products, 30 of which are affected. The material will be created by medical education companies, and will include patient-education brochures.

That’s nice, but a story on FDA Law Blog was clear about the program’s deficits: “[M]ore than three years after beginning the opioid REM process, the final REMS … amounts to essentially a mere education and monitoring program. …[D] espite FDA’s statement in 2009 that “voluntary programs have not been successful in getting us where we need to go with maintaining access to legitimate patients and dramatically decreasing the serious adverse event reports,” the healthcare professional education provided by the REMS is in fact voluntary.”

And, as noted on MedPage Today, the guidelines were criticized not only because doctors aren't required to educate themselves about the drugs, but for empowering the industry that produces the problematic products to sponsor education about them and for not including powerful short-acting narcotics such as Vicodin.

The new REMS sound like a language course that teaches students all about nouns, pronouns and adverbs, but lacks lesson plans for conjugating verbs.

As Dr. Andrew Kolodny, chair of psychiatry at Maimonides Medical Center in New York, told MedPage, "These educational programs are likely going to do more harm than good. Nowhere does it say that prescribers should tell patients these drugs are addictive. And these programs give the implied message that there's evidence for using opioids in long-term, noncancer chronic pain."

We addressed some of these issues a few months ago in our post about the demise of American Pain Foundation, which had demonstrated a shocking conflict of interest between its information campaign and its pharmaceutical sponsors.

Kolodny said that the new, unimproved REMS offers the same version that the FDA’s own advisory committee deep-sixed two years ago. He said the REMS is a windfall for the medical education companies retained by the drug manufacturers, about five of which already generate much of the industry-sponsored education for opioids.

A better approach ties a practitioner’s DEA license or certification to his or her mastery of opiate indications, risks and benefits. For example, Kolodny noted, is a drug called buprenorphine (Suboxone), an opiate that also treats addiction. Before a doctor may prescribe it, he or she must complete an eight-hour class.

It’s not a lot to ask when you consider that:

• Prescription drug abuse is the fastest growing drug problem in the U.S.


• Approximately 23 million prescriptions for extended-release and long-acting opioids were written in 2011.


• In one recent year in the U.S. one death due to drug overdose occurred every 19 minutes.


• The recent increase in unintentional drug overdose deaths has been driven by the increased use of prescription narcotics.


• In one recent year, for every unintentional overdose death related to narcotics, nine patients were admitted for substance abuse treatment, 35 visited emergency departments, 161 reported drug abuse or dependence and 461 reported nonmedical uses of these drugs.


• In the 10 years between 1997 and 2007, the distribution of morphine per person increased more than 600 percent. According to the CDC, that’s enough morphine for everyone in the U.S. to take a typical, 5 mg dose of Vicodin every four hours for three weeks.

The FDA estimates that there are 320,000 prescribers of long-acting narcotics in the U.S.; 1 in 4 is expected to be trained by the end of the program's first year. The goal is to have 6 in 10 trained by the third year.

But doctor education programs alone can’t reduce the terrible toll of narcotic abuse and industry-wide ignorance of best pharmaceutical intervention practice. Practices such as “doctor shopping,” in which consumers go from doctor to doctor in search of prescriptions for illegal pharmaceuticals, or seek out multiple practitioners who each prescribe the desired drug, even for a legitimate condition, have to be addressed. There are state laws against such behavior, but their routine enforcement is wanting.

“[O] nly a few states,” according to the CDC, “have laws regulating for-profit clinics that distribute controlled prescription drugs with minimal medical evaluation. Laws against such ‘pill mills’ as well as laws that require physical examinations before prescribing might help reduce the diversion of these drugs for nonmedical use.” (We recently retold the story of one pill-pushing doctor who did get busted for murder related to fatal overdoses.)

The CDC also says the plug can be pulled on doctor shopping by tracking prescriptions in a database, and by insurance companies paying attention to claims processing and limiting reimbursements for narcotic prescriptions to designated doctors and pharmacies.

A meatier set of guidelines by the FDA also would be nice.

The advent of Medicare’s Part D drug plan introduced everyone to the concept of the “donut hole.” That’s the point at which prescription drug coverage ceases for a period during which the plan member pays full price. The gap closes when the patient has spent a set amount for drugs, and subsidies resume. As reported by Reuters Health, research has shown that this gap prompts seniors to stop taking medications for heart problems, diabetes and, now, depression.

According to the researchers of a new study published in the Archives of General Psychiatry, when these patients stop taking antidepressants, their risk of relapse increases. Such behavior, they said, “poses a serious risk.”

Once beneficiaries pay a deductible of a few hundred dollars, Part D drug plans usually cover 75 percent of drug costs until the threshold figure is reached. This year, for standard coverage, that amount is nearly $3,000. Then patients must shell out another $3,700 (amounts vary according to plan) before coverage resumes.

If the Affordable Care Act survives the current political upheaval, the donut hole will expire in 2020, when the legislation mandates that drug coverage be constant. But that’s a long time away, especially if you’re a senior citizen.

We’ve discussed how the insurance coverage options available to supplement Medicare are so confusing that seniors are less likely to enroll for additional coverage. But the study makes clear, however, that they are less likely to forgo their drugs if they have it.

The study involved more than 22,000 Medicare beneficiaries who had been diagnosed with depression and were prescribed antidepressants. Data was collected starting in 2007, the year after the Part D plan was initiated. Nearly 3,000 study subjects had supplemental insurance that filled the gap for generic drugs. Another 11,500 had complete coverage from other sources, including low-income subsidies. But more than 7,500 were stuck paying the gap amount.
Nearly 7 in 100 people who had generic drug gap coverage ceased taking their antidepressant meds, but more than 12 in 100 with no coverage did.

As the study notes, depression affects 13 in 100 Medicare beneficiaries 65 years or older. Many have additional chronic physical conditions. Treating and maintaining treatment of late-life depression with antidepressants prevents recurrent episodes of major depression. Caregivers generally recommend these patients take antidepressants for two years.

It’s a bad idea to stop taking these drugs cold turkey. As the lead researcher wrote, "If patients discontinue their appropriate medication therapy abruptly, they could be placing themselves at risk for medication withdrawal effects [including include dizziness, gastrointestinal distress, disturbing dreams, fatigue and irritability] and for (depression) relapse or recurrence."

Although the study didn’t find that rates of hospitalization were higher for the no-gap coverage group than the others in the study, the depressed elderly population remains vulnerable to the Part D donut hole.

If you or a loved one is in this situation, help is available. Contact the manufacturer of the relevant drug—they often have coupons or rebate/subsidy programs for the financially pinched. That link also includes contact information for other prescription assistance organizations, as well as general resources for seniors. For general information about Medicare’s prescription drug coverage, link here.

Many health and medical journalists, and watchdogs of the practice of medicine, have noted a peculiarly American phenomenon: “disease mongering.” As defined by journal PLoS Medicine, disease mongering is “the selling of sickness that widens the boundaries of illness and grows the markets for those who sell and deliver treatments.”

We’ve discussed the topic before, and no doubt will again because it’s found in several guises.

Instead of preventing disease and maintaining health, disease mongering is about conflating common complaints into pathology; it’s about fear and overtreatment, about selling drugs and therapies to “patients” who, by more measured analysis, are really just people with transient or nonexistent problems.

A recent post on KevinMd.com by Dr. Edward Pullen discussed a current representative of disease mongering: low testosterone. “It seems like every day in the office I see at least one man concerned about testosterone deficiency. If you look at the symptoms of testosterone deficiency, most of us have one or more of these symptoms at least some of the time. Fatigue, depression, weight gain, lack of energy, reduced sex drive, loss of physical strength and moodiness are all described as symptoms typical of testosterone deficiency.”

True testosterone deficiency, as defined by the National Institutes of Health, is known as hypogonadism, and can be related to dysfunction in the brain or the testes. It can reflect genetic disorders, or result from trauma, radiation or chemotherapy. It’s common among people with diabetes, chronic pain, metabolic syndrome, inflammatory arthritis, chronic obstructive pulmonary disease (COPD) and kidney disease. But absent a clinically diagnosed reason for flagging testosterone, is it a medical problem worthy of treatment?

HealthNewsReview.org doesn’t think so. It recently alluded to a couple of studies in the Medical Journal of Australia about low-testosterone campaigns (here and here) in a country that has seen at least a twofold increase in total expenditure on testosterone prescriptions in the last two decades, and where direct-to-consumer marketing is not permitted (unlike in the U.S.). Those researchers, finding an insidious effort to juice the drug market despite no medical necessity, called for strict enforcement of the law and sanctions for companies that violate it.

As Pullen explained, defining “low” in testosterone levels is tricky—population estimates range from nearly 3 in 100 men to nearly 40 in 100, the latter figure reflecting people with the diseases mentioned above. Even if it seems appropriate to prescribe testosterone (known as hormone replacement therapy, or HRT), there is cause for pause, because the long term effects are unknown. Some men who take testosterone create additional red blood cells, a condition called polycythemia, that can cause lead to stroke. Although some dire risks are apparent, who knows about the potential for heart disease, prostate enlargement or cancer, all of which are of concern?

It’s reminiscent of the situation with female HRT when, after decades of treatment primarily to relieve the symptoms of menopause, scientific studies showed an increased risk of breast cancer and cardiovascular disease that prompted most practitioners to cease prescribing hormones for most women except for short-term treatment.

Do most of the common, if unpleasant, side effects of menopause really constitute a disorder? Or is pandering to temporary discomfort, even if extreme, more a matter of disease mongering than a reasonable medical response?

Other factors enter into the decision about male HRT. It can be expensive (one review yielded a cost of $330 per month for one brand name), and the the dose delivery can be erratic. Also, according to the Mayo Clinic, common if not life-threatening side effects of testosterone replacement therapy can include:

• sleep apnea — a potentially serious disorder in which breathing repeatedly stops and starts during sleep;


• acne or other skin reactions;


• enlarged breasts;


• limited sperm production or testicle shrinkage.

If you wonder if HRT might address symptoms you think are testosterone-related, the first step is to get a blood test identifying your levels. The next step is to ask these questions of your doctor:

1. What is a normal testosterone level for me? Are my symptoms from low testosterone or something else?
2. Are my symptoms temporary and/or intermittent?
3. If I take HRT to alleviate my symptoms, what are the risks?
4. Will I have to take HRT indefinitely?
5. What are the alternatives?

And ask yourself: Am I responding to an advertising campaign? Am I experiencing a natural part of life that requires not medicine but coping skills?

We’ve written a lot about pharmaceutical company misbehavior because pharmaceutical companies misbehave a lot, and their actions can pose serious health harms.

One such breach of decency and law was so monumental that last week it made top-of-the-news headlines across all media. GlaxoSmithKline, manufacturers of well-known drugs including Flonase, Levitra and Zantac, agreed to plead guilty to three criminal misdemeanor charges of illegally marketing some of its other drugs and withholding safety information from government regulators.

In November, it had agreed to pay $3 billion to settle several lawsuits over its antidepressants Paxil and Wellbutrin, and its diabetes drug, Avandia. It was the largest health-care fraud settlement in U.S. history. But not until last week did the company plead guilty to the criminal charges, and the details of the complicated case emerge. The fine represents $1 billion in fines and $2 billion to settle civil liabilities.

As noted in the Wall Street Journal, it was the fourth time Glaxo has settled with the U.S. government in recent years. This was not only its most expensive resolution, it was the most far-reaching.

The illegal activity for the depression drugs involved promoting them for uses that hadn’t been approved by the FDA, a practice called off-label marketing. Glaxo also withheld data that showed that Avandia had been linked to an increased risk of heart problems.

Using outside ghostwriters to prepare a medical journal article falsely reporting that Paxil was effective in treating depression in children, Glaxo then used the piece to promote it for the adolescent market, never mind reports of increased suicidal tendencies among teens who took the drug. Glaxo promoted Wellbutrin, which was approved only to treat depression, for weight loss, substance addiction, attention deficit hyperactivity disorder (ADHD) and, most colorfully, for sexual dysfunction. Sales reps referred to it as “the happy, horny, skinny pill.”

All false claims, and all dangerous, especially when you consider that the robust marketing effort financially rewarded sales people according the number of prescriptions they persuaded doctors to write.

And get this: Prosecutors don’t know how much money the company made by promoting the drugs off-label for so many years, so it’s possible the revenue from dirty deeds exceeded even the $3 billion the company will pay. Is it a penalty or an investment?

Avandia, like Paxil and Wellbutrin, remains on the market in the U.S., but the packaging now bears a black-box warning about heart risk. (European regulators deemed it too risky for everybody, and withdrew it from the market in 2010.)

The settlement also addresses conduct the Justice Department says resulted in the overpayment of public funds for drugs issued via programs such as Medicaid. That included kickbacks paid to doctors. At some point do you start to wonder which organization is capable of whacking more people, the Mafia or Big Pharma?

Settlement terms include an “executive financial recoupment program” requiring changes in Glaxo’s executive compensation policies. They permit the company to recoup bonuses and incentive pay from employees who engage in significant misconduct. This seems thin: How about using docked pay to compensate victims?

In 2003, some company insiders filed a lawsuit against Glaxo under the Federal False Claims Act, which prohibits people or businesses from defrauding the government. The whistleblowers, whose information was critical to the government’s case, will receive a handsome share of the settlement penalty.

The rest of us will benefit, one hopes, from the hammer coming down hard, and the rest of the world hearing about it. But we agree with Dr. Sidney Wolfe, director of the Public Citizen Health Research Group: “Until more meaningful penalties and the prospect of jail time for company heads who are responsible for such activity become commonplace, companies will continue defrauding the government and putting patients' lives in danger.”

Who among us has not received prescription drugs in a container bearing more labels than a NASCAR vehicle has decals?

Information and warning labels are applied to medicine bottles and packages, the thinking goes, because it’s the most immediate, and therefore most effective, delivery system for patient safety information. Except that it’s not working, according to a recent study published in PLoS One.

The study found that only half of its participants looked directly at all of the warning labels; more than 1 in 5 didn’t look at any. This is rather alarming when you consider that approximately 4 million Americans experience adverse reactions to prescription medications every year. Some are relatively mild, such as minor rashes, but others can be fatal. The study’s researchers, from Michigan State University, concluded that many such events could be avoided if warning labels were more effective.

Researchers studied how two groups of patients—young adults and those older than 50—reacted to the small, colorful stickers applied at the pharmacy where the medicine was dispensed. They tracked patients’ eye movements when they got the drugs, and later tested their memory recognition about the information printed on the labels. The older group failed more often initially to read labels, but when they did, the age-related differences weren’t significant. That suggests that group differences were related not to the ability to remember, but to pay attention.

That’s important because older people are generally recognized to be at greater risk of an adverse drug event: On average, nearly 1 in 3 people older than 65 take 10 different medications daily.

“Given our results,” said Laura Bix, associate professor in MSU’s School of Packaging, “we are recommending a complete overhaul of the design and labeling of the ubiquitous amber bottles [and plastic containers], which have seen little change since their introduction some 50 years ago. Our initial recommendations would be to move all of the warnings from the colored stickers to the main, white label, which 100 percent of the participants read, or to reposition the warnings so that they can be seen from this vantage point.”

So if drug labels are better at capturing a consumer’s attention initially for warnings such as “do not consume alcohol while taking this medicine,” or “for external use only,” the risk of a problem drops.

Here’s where effective medicine crosses the boundary of biological science. MSU Mark Becker, assistant professor of cognition and cognitive neuroscience said, “By applying basic research on the control of attention to the design of labels, we may greatly improve their effectiveness.”

Until labels that effectively communicate important drug information become standardized across all forms of prescription packaging, anyone taking any drug—even one available over the counter—should read all labels and enclosures for every drug he or she takes. The only way to minimize the risk all medicines carry is to know as much as you can about how it behaves in your body, alone and when taken with other chemical compounds.

Warfarin, the generic name for the most widely prescribed oral anticoagulant (blood thinner) in America, is used to prevent thrombosis (blood clots) and thromboembolism (blood clots that migrate throughout the body). People diagnosed with atrial fibrillation (rapid or irregular heartbeat), narrowed coronary arteries, who have had valve or stent replacement surgery or have a history of blood clots in the legs or lungs, often are prescribed warfarin, or its most common brand name, Coumadin.

The blood thinner can be a lifesaver for people at risk of stroke or heart attack caused by blood clots. (To learn more about maintaining heart health, see our newsletter, “A Healthy Heart: Unlocking the Key to Long Life.”)

But according to the Harvard Medical School heart health newsletter, these patients must ensure that they’re not posing additional risks by taking warfarin with certain antibiotics and antifungal drugs, which enhance warfarin’s blood-thinning effect, and possibly prompt internal bleeding.

The amount of warfarin in the bloodstream is measured by clotting time, and is expressed by the international normalized ratio, or INR. The higher the INR, the longer it takes blood to clot. In warfarin patients, medical practitioners look for a ratio of 2 to 3, although individual numbers might vary. Antibiotics affect these levels. Somebody who’s stable at 2.5 and takes an antibiotic can measure 5. If that level is sustained, it can cause gastrointestinal bleeding; a bump on the head, as the newsletter notes, can prompt bleeding in the brain.

Because antibiotics affect people differently, warfarin patients must be evaluated carefully and monitored regularly as soon as they begin a long-term antibiotic regimen. (With a short-term prescription, such as that used for two or three days in advance of dental work, an increase in INR isn’t necessarily worrisome, as the antibiotic clears the system quickly.)

Potential problems must be monitored particularly with broad-spectrum antibiotics, including erythromycin, penicillin and ciprofloxacin. Sometimes their doses must be lowered to accommodate warfarin patients.

In addition to pills, topical antibiotics—those delivered via ointment, cream or suppository—also are absorbed into the bloodstream and interfere with warfarin. Antifungal cream is a prime example. It’s often prescribed to women with vaginal yeast infections.

Like all drugs, warfarin taken alone carries potential side effects and risks. A recent story in Forbes noted that last year, warfarin was the second most prevalent drug in FDA safety reports “and has been high on the FDA list for many years.” It was the subject of 1,106 serious adverse events, including 72 deaths.

Although doctors generally discuss the risks of antibiotics with their warfarin patients, there’s plenty of opportunity for an adverse event if:

• a patient doesn’t understand the potential significance of the drug-drug interaction;


• a patient forgets the drug information;


• a doctor prescribing the antibiotic is different from the doctor prescribing the warfarin, and communication between the two falters;


• a patient doesn’t comply with INR testing;


• the drug-interaction alert function in the doctor’s computerized medical records is inoperative and/or the medications it lists is out of date;


• a patient uses different pharmacies for filling the warfarin and antibiotic prescriptions, so the pharmacists aren’t aware that a warning should be issued;


• a patient gets an antibiotic sample or handwritten prescription, bypassing a computer system alert.

If you take drugs, especially long-term prescriptions you renew automatically, here’s another reason not to be complacent in the administration of your health care. A report published this month in the Archives of Internal Medicine found significant flaws in how drug recalls are communicated to medical providers and the consumers affected by them.

Recalled drugs are denoted by “class,” which categorizes them according to the degree of danger.

Class III recalls concern products not likely to prompt an adverse health reaction. They might violate FDA labeling or manufacturing regulations, such as a container defect or odd color.

Class II recalls concern products that might prompt a temporary or minor health issue, such as a drug that isn’t as strong as advertised, but isn’t used to treat life-threatening situations.

Class I recalls concern dangerous or defective products that pose a danger of a serious health problem, or even death. They might be contaminated with a toxin, or contain unlabeled allergens. Defective high-risk devices, such as heart valves, also fall into this category.

The new study, as reported on AboutLawsuits.com, found scary flaws in the FDA’s notification system for Class I drug recalls.

“Clinically important drug recalls occur nearly once per month in the United States,” the researchers wrote, “and usually involve thousands of affected units distributed nationwide or beyond. Despite recent efforts by the FDA to address the drug recall burden, health-care providers may be inadequately informed about clinically important recalls that threaten patient safety.”

The FDA is supposed to issue Class I recall notifications through its Recall Alert System and its MedWatch adverse event reporting program. But between 2004 and 2011, the researchers found that 91 of 1,700 drug recalls were unreported Class I recalls.

Of the 91 Class I recalls, the Recall Alert System issued notices for only 55. MedWatch issued notices for 18 of the remaining 36 that were classified as Class I. But 18, or about 1 in 5, were not reported to doctors by any FDA system.

Not only is the lack of information a shocking deficiency of dangerous proportions, but doctors can be confused about which recalls are important and which aren’t—both systems purport to report every drug recall regardless of its intended consumer. Drugs used to treat animals are reported the same way as Class I drugs, and that could be lethal for humans.

“[T] he Class I recalls that are communicated through the Recall Alert System,” the researchers wrote, “become buried in a system that is also used for recalls that have little or no bearing on patient care. It may be difficult for providers who subscribe to and rely on these alerting systems to identify those recalls that are of particular importance.”

The researchers said their analysis was limited because only 5 in 100 reports for Class I recalls noted adverse events, which they thought underestimated the true frequency with which recalled drugs cause harm. They cited as an example heparin, whose recall report in 2008 did not mention adverse events. But the FDA found several, including deaths, associated with contaminated heparin.

They also did not evaluate other means by which health-care professionals might receive drug recall information, such as “Dear Doctor” letters from manufacturers.

But they concluded that a comprehensive new strategy is required to ensure that medical providers are notified efficiently and fully when Class I recalls occur.

In addition to improving communication, they also called for a system to track the distribution of affected products throughout the supply chain, all the way to the consumer. Electronic tagging (radiofrequency identification technology) would enable pharmacies to identify and notify affected individuals as soon as a recall is initiated.

If you take a certain drug or drugs, you should regularly check MedWatch for information. In addition, you can subscribe here to a recall information mailing list distributed by the U.S. Consumer Products Safety Commission.

Martha Deed is exactly the person anyone would want as his or her patient advocate. A psychologist and member of the Consumers Union network of patient advocates, she is trained in patient advocacy and has a profound understanding of patient safety issues.

Yet when her own chronically ill daughter was subjected to a daunting cross-current of hospital specialists and treatment, even Deed felt like a sock being tossed around in an industrial washing machine.

She recently wrote about the experience on Sporkworld.org, and came away with valuable lessons for all.

As designated advocate for her 36-year-old daughter, Millie, who suffered from Behcet’s disease, an obscure autoimmune disorder, Deed had been through multiple medical emergencies and hospitalizations. She knew her daughter’s wishes, her response to various medications and her complicated medical history.

When Millie contracted a respiratory infection, few of Millie’s treatment providers had ever encountered a person with Behcet’s and none had ever spoken to her about how she wished her illness to be handled.

On admission to the hospital, Deed soon learned the limits of her superior knowledge. “I knew only what Millie’s previous illnesses had taught me. Each new hospitalization required a steep learning curve. [This] hospital was not treating Millie for Behcet’s. They were treating her in the ICU for respiratory failure due to swine flu. Behcet’s, to them, was an interesting side issue that they had little time for in an emergency.”

What ensued was a torturous adventure trying to communicate with uninformed professionals and coordinating care for two diseases whose treatment options often were contradictory. Medications that exacerbated Behcet’s were given to Millie without Deed’s knowledge, and sometimes in defiance of her directions.

We’ve written frequently about patient advocacy, including “Bringing an Ally with You to the Doctor’s Office,” “Protecting a Loved One in the Hospital” and “When the Doctor Isn’t Sure: What You Can Do.”

After Millie’s death, Deed learned:

• If you do not have accurate information about your family member’s treatment, you cannot advocate effectively.


• If staff does not accept documented medical facts about the patient, the hospital’s patient safety efforts may fail.


• Patient safety personnel cannot work effectively if there are gaps in handling a patient’s concerns.


• If you don’t know who is in charge, your concerns may not be addressed.

If hospitalization is a surprise:
1. Read the hospital’s orientation material carefully. Find out who is in charge of your loved one’s case. Be present for rounds by that physician.
2. Make sure that others are available to visit and comfort the patient if you are engaged in advocacy.
3. Have someone stay with the patient as close to 24/7 as possible--problems can occur day or night. Do not attempt to do it all by yourself.
4. Get some rest yourself so that you can remain helpful and clear thinking.
5. Keep a log so as not to lose track of what is happening with your loved one’s care. Include notes of any contact with medical staff. This can help prevent misunderstandings as well as mistakes.
6. The hospital probably prefers a single contact person. But that person—you, the patient advocate—can benefit from discussing the patient’s treatment with someone who knows the patient well and is trusted by him or her. The back-up can help identify communication or treatment gaps.
7. Be polite, even in an emergency in which you must engage the highest levels of hospital hierarchy.

Acetaminophen is one of the most common pain relievers in the U.S. It’s also one of the most overused.

A new study in the Journal of General Internal Medicine found that nearly 1 in 4 U.S. adults misunderstands what is a safe dose of Tylenol, the most widely used brand name version of acetaminophen.

Not knowing what is safe, of course, invites overdose. We’ve written in the past about the perils of too much acetaminophen for both children and adults.

The most serious complication is liver damage, which can prompt liver failure and the need for a liver transplant. FDA figures show that more than 50,000 emergency room visits, 25,000 hospitalizations and 450 deaths annually are the result of acetaminophen overdose.

The maximum amount adults should take is 4 grams (4,000 mg) per day.

As noted in a story on AboutLawsuits.com, researchers for the new study found that nearly 1 in 2 adults is at risk of overdosing because more than one medication containing acetaminophen often are taken simultaneously.

The compound is found in many different over-the-counter drugs, and is popular for reducing fever as well as for pain relief.

In the new study, nearly 1 in 4 patients showed a tendency to overdose on a single over-the-counter acetaminophen product by exceeding four grams per day. Five in 100 exceeded six grams per day.

People more likely to exceed recommended limits by taking more than one product containing the drug were of limited literacy and/or were heavy acetaminophen users.

But the problem isn’t limited to people self-administering the medicine. Last month, AboutLawsuits reported findings presented to a medical conference on digestive diseases that hospitals routinely provide patients with excessive doses of acetaminophen.

Those researchers, from Thomas Jefferson University Hospital in Philadelphia, found that 2 or 3 in 100 hospital patients are given too much acetaminophen at least one day during their stay.

AboutLawsuits also noted that research published last year showed that even small acetaminophen overdoses are risky. Such “staggered overdoses,” it said, were more likely to cause serious and potentially life-threatening injury from small, accidental overdoses than from large acetaminophen overdoses, such as in a suicide attempt, because the risk of liver damage is not as easily detectable.

Tylenol’s manufacturer, Johnson & Johnson, has been sued several times by people alleging that the company sold the popular painkiller for years without providing adequate warnings about the risks associated with excessive amounts.

Patrick Malone won a landmark lawsuit, Benedi v. McNeil-PPC, against the manufacturer of Tylenol in 1995 for its deficient warnings for alcohol drinkers.

According to the National Institutes of Health, symptoms of acetaminophen overdose include:

• nausea;


• vomiting;


• loss of appetite;


• sweating;


• extreme tiredness;


• unusual bleeding or bruising;


• pain in the upper right part of the stomach;


• yellowing of the skin or eyes;


• flu-like symptoms.

The teen guide is aimed at the parents, coaches, teachers and school health-care providers who influence the attitudes and behavior of younger folks. The guide for college students is geared toward campus leaders, and the effort to reach seniors emphasizes the dangers of drug interaction and that many medications contain acetaminophen.

Always read the label of any medicine you take to relieve pain and lower fever. A list of brand names containing acetaminophen is available at the National Institutes of Health.

If you take acetaminophen:

The latest player in the ongoing story of counterfeit drugs is Adderall, a controlled substance prescribed to treat attention deficit hyperactivity disorders (ADHD) and narcolepsy.

Last week the FDA issued a warning to consumers that counterfeit 30 mg tablets of Adderall were available for purchase via the Internet. “The counterfeit versions of Adderall should be considered as unsafe, ineffective and potentially harmful,” the FDA said.

Preliminary lab tests showed that the counterfeit meds contained the wrong active ingredients, replacing the legitimate compounds with tramadol and acetaminophen, which treat acute pain.

For patients who need Adderall, the situation can be dire: Adderall is on the FDA’s drug shortage list, thanks to supply problems manufacturer Teva Pharmaceuticals is having with the active ingredients. The FDA warned that rogue websites and distributors take advantage especially of medicines in short supply, and that consumer must exercise extreme caution when purchasing them online.

Purveyors of the bogus drugs don’t require a prescription, which is a huge red flag right there.

Authentic Adderall 30 mg tablets are round, scored, orange/peach in color and are embossed with “dp” on one side and “30” on the other. The counterfeit pills are round, white, smooth and bear no markings. Click here for photos of both.

In addition, Teva packages Adderall 30 mg tablets only in 100-count bottles with the National Drug Code listed—0555-0768-02. Counterfeit Adderall comes in a blister package that may have misspellings.

Do not take tablets you suspect might be counterfeit, or if you are unsure. Telephone the FDA for additional information (888 463-6332) and contact your doctor if your pills are suspect and/or you can’t find a supply of legitimate medicine.

Also, report any negative side effects or adverse events that you believe are the result of taking Adderall, whether or not you know if it’s counterfeit. Contact the FDA’s MedWatch Safety Information and Adverse Event Reporting Program here. You can also request a reporting form by calling (800) 332-1088.

If you think you have counterfeit Adderall, contact the FDA’s Office of Criminal Investigations here, or call (800) 551-3989.

It has been 10 years since the U.S. Preventive Services Task Force (USPSTF) raised a red flag of concern for women who take hormone replacement therapy (HRT). A systematic review of scientific research published on the subject since 2002, the task force concluded last week, confirms the initial call for caution.

HRT is most often prescribed to alleviate the symptoms of menopause, including hot flashes, vaginal dryness, sleep disturbances and mood swings. Although HRT might be appropriate for people in this situation, the task force said that the risks for most women taking HRT for the long term still outweigh any benefits it confers in preventing chronic conditions.

As reported widely, including on MedPage Today, the hormones at issue—estrogen and progestin—do help prevent bone fractures, used alone and together. But they increase the risk of stroke, thromboembolisms (blood clots that dislodge and move through the circulation system), gallbladder disease and urinary incontinence.

The review of HRT was published on the Annals of Internal Medicine.

Most women prescribed HRT are given estrogen plus progestin because unalloyed estrogen increases the risk of uterine cancer, so plain estrogen is generally prescribed only for women who have had a hysterectomy. The new study indicates that the estrogen/progestin compound also increases risk for breast cancer and dementia. Estrogen alone decreases the risk for breast cancer.

In 2002, the USPSTF recommended against routine, long-term HRT use, and in 2005 recommended against long-term us of estrogen alone. The recommendations did not address short-term use of HRT to relieve menopause symptoms.

The new review of nearly a decade’s worth of clinical studies evaluated HRT’s effect on cardiovascular disease, cognitive decline, osteoporosis (thinning of the bones) and cancer.

Use of estrogen alone showed significant decreases in invasive breast cancer and mortality. Use of estrogen/progestin showed significant decreases in diabetes. Bone fractures were reduced significantly with both hormone regimens in some studies but not others.

But the harms significantly increased by one or both hormone replacement regimens were:

• invasive breast cancer (estrogen plus progestin);


• stroke (both);


• deep vein thrombosis (DVT/blood clot—both);


• pulmonary embolism (blood clot in the lung—estrogen plus progestin);


• breast cancer mortality (estrogen plus progestin);


• lung cancer mortality (estrogen plus progestin);


• gallbladder disease (both);


• probable dementia (estrogen plus progestin);


• urinary incontinence (both).

The corresponding numbers for estrogen plus progestin, according to the study, were just as unfavorable.

There might be benefits worthy of HRT (and different harms) for certain people with certain conditions, for which the study was inconclusive. Such different results could occur because of differences in age, type of hormone therapy, natural versus premature menopause or other medical conditions.

But the bottom line for most women is that hormone replacement therapy generally should be used only for short-term relief of menopausal symptoms. Individuals should discuss its suitability for other concerns only in the context of a complete medical history and an understanding of the risks.

The concept of coordinated care is considered a best practice, but in light of a recent survey and story by NPR, the Robert Wood Johnson Foundation and Harvard School of Public Health, it’s hardly a widespread one.

A few years ago, we wrote about what happens to hospital patients when the facility’s right hand doesn’t know what the left hand is doing. The story told how the lack of coordinated care resulted in 1 in 5 Medicare patients being readmitted to the hospital within 30 days.

Earlier this year, we reported that some health insurers are beginning to appreciate the wisdom of coordinating patient care in terms of both health outcomes and cost savings.

Coordinated care involves a therapeutic plan that integrates the efforts of all of the patient’s medical and social service providers. It might designate a single person to manage all of the collaborators or simply might be an understanding they share to ensure efficiency and communication. The point is to maximize resources, minimize duplicate procedures, reduce costs and, ideally, prevent harm.

That didn’t happen for Andrew Dasenbrock, one of the subjects detailed in the NPR story.

A 32-year-old a self-employed IT consultant, Dasenbrock says he can't afford health insurance. When he woke one night with intense stomach pain — "like shards of glass traveling through me," he said—he went to an urgent care center nearby. Doctors ran several tests, couldn’t settle on a diagnosis and sent him to the hospital.

The hospital was part of the same system, but its staff was not alerted to Dasenbrock’s arrival, nor were his records transferred. He was forced to fill out the same questionnaires and repeat all the same diagnostic tests. He remained in excruciating pain.

The hospital diagnosed an ailment that, while painful, wasn’t serious and required only that Dasenbrock ingest a lot of fluid. He went home. Two days later he received two bills totaling thousands of dollars.

"I laid the two bills next to each other and it was literally word for word, letter for letter and line item by line item the same charges ... for all the tests I had gone through," Dasenbrock said. He had to pay double what he should have for his care.

Another tale was told by Jacki Bronicki, whose father was 80. He had Parkinson’s disease, but the retired engineer and physics teacher was mentally acute and responding well to his treatment.

Last year he fell, broke three ribs and was admitted to the hospital. His mental state began to deteriorate by the second day. "He wasn't even coherent by the third day," Bronicki said.

Bronicki said that the parade of doctors who saw him seemed to assume that his confusion was, for him, normal, and reflected his age and condition. Bronicki said she had to explain to each new doctor that he had Parkinson's, that his mental deterioration was not his normal, that he usually was coherent.

Finally, a neurologist finally figured out that all the different doctors had prescribed different pain medications, and the drugs were interfering with Brown's Parkinson's medication. That caused his mental deterioration and made his limbs rigid.

His prescriptions were realigned, and he improved. But Bronicki and her sisters felt they had to remain at his hospital bedside 24 hours a day to prevent another medication error. And, she reported, "He has a lot more dementia than he had a year before. He can't walk anymore. And I'm not sure if it would have normally progressed like this, or if we really sped it up."

It wasn’t they who sped it up; more likely, it was the lack of communication and coordination among all of his caregivers.

Certainly, many of the survey respondents were pleased with their care. But of people hospitalized in the last 12 months:

• 30 percent said doctors, nurses and other health-care professionals communicated poorly with each other;


• 24 percent said doctors, nurses and other health-care professionals didn’t communicate information about their condition or treatment.

Here's another tale of Big Pharma insinuating itself into places it doesn't belong, to the detriment of quality care and patient safety.

Established to support patients with chronic pain, their families and the health-care professionals who serve them, the American Pain Foundation claimed to be the pain community’s largest advocacy group. Early this month, it abruptly shuttered its operation, attributing its demise to economic circumstances.

As several news organizations reported, that’s hardly the whole story.

Given the boom in prescription pain medicine—according to Marketplace.org, prescriptions for painkillers such as Oxycontin and Vicodin have quadrupled in the last decade—Americans clearly are hurting. You’d think there would be plenty of support for an organization that salved the pain.

But as explained in an investigative report by ProPublica, the foundation shutdown had to do with a U.S. Senate committee investigation into makers of narcotic painkillers and groups that champion them. According to ProPublica, 9 of every 10 dollars of the foundation’s funding in 2010 came from the drug and medical-device industry.

And—surprise!—its guidelines for patients, journalists and policymakers had minimized the risks associated with opioid painkillers and had exaggerated their benefits.

Senators Max Baucus, D-Mont., and Charles Grassley, R-Iowa, sent letters to the foundation and drug companies citing an "an epidemic of accidental deaths and addiction resulting from the increased sale and use of powerful narcotic painkillers."

Drug companies, they wrote, "may be responsible, at least in part, for this epidemic by promoting misleading information about the drugs' safety and effectiveness."

The senators are looking into the whole pain-control industry and medical oversight agencies to expose the financial connections among them. In addition to the American Pain Foundation and drug makers, recipients of the letters included the American Academy of Pain Medicine, American Pain Society, the Federation of State Medical Boards (the trade group for agencies that license doctors) and The Joint Commission (an independent nonprofit that accredits hospitals).

The U.S. Government Accountability Office (GAO) reported in 2003 that the Joint Commission had partnered with Purdue Pharma, the maker of Oxycontin, to distribute pain educational materials. In 2007, Purdue had pleaded guilty to federal criminal charges that it misled regulators, physicians and consumers about Oxycontin's risk of addiction.

No one denies that opioids might be appropriate for people in serious pain. But like any other drug, their benefits must be measured against their potential harm, and you can’t do that when manufacturers and so-called “advocates” supply inaccurate or incomplete information.

As quoted in the ProPublica story, Dr. Andrew Kolodny, chairman of psychiatry at Maimonides Medical Center in Brooklyn, N.Y., and president of Physicians for Responsible Opioid Prescribing, said, "These groups, these pain organizations … helped usher in an epidemic that's killed 100,000 people by promoting aggressive use of opioids. What makes this especially disturbing is that despite overwhelming evidence that their effort created a public health crisis, they're continuing to minimize the risk of addiction."

Sales of these potent drugs have risen 300 percent since 1999. And opioids were involved in 14,800 overdose deaths in 2008, more than cocaine and heroin combined. In 2009, the use and misuse of the drugs were cited in more than 475,000 emergency department visits, nearly doubling the 2004 number. The figures come from the Centers for Disease Control and Prevention (CDC).

One in 8 high school seniors surveyed for a research paper in the Archives of Pediatrics & Adolescent Medicine said they had used prescription opioids for nonmedical reasons.

Another report in the Journal of the American Medical Association found that the rate of newborns diagnosed with drug withdrawal jumped threefold from 2000 to 2009. The rate of mothers using opioids at the time of delivery was five times higher in 2009.

Typically, medical professionals and patient advocacy groups acknowledge that drug overdoses are a legitimate concern, but say that most deaths involve illegally obtained drugs. They also say that patients' risk is low if they do not have addictive personalities, and people who suffer from serious pain should not be deprived of relief.

No, they shouldn’t. But narcotic manufacturers also shouldn’t be bankrolling advocacy groups whose job is to provide objective and complete information about drugs.

Here’s another arrow for the quiver of people exasperated with government.

As part of its health-care reform, the Obama Administration proposed that drug companies be made to disclose payments they make to doctors for research, consulting, speaking, travel and entertainment. The rationale, as reported by The New York Times, was evidence that such payments can influence treatment decisions and boost costs by encouraging the use of more expensive drugs and medical devices.

Disclosure, the thinking goes, would make doctors more disposed toward making decisions in the best interests of patients instead of their bottom lines. As we’ve reported, drug and device company largess can be ripe for conflicts of interest.

According to The Times, about 1 in 4 doctors takes cash payments from drug or device makers; nearly 2 in 3 accept routine gifts of meals for themselves and their staff. The Times also concluded that doctors who take money from drug makers often practice medicine differently from those who do not—they’re more willing to prescribe drugs in risky and unapproved ways, such as prescribing powerful antipsychotic medicines for children.

Some companies have begun posting some payment information on their web sites, sometimes as the result of legal settlements with the federal government. Under the new proposal, if a company has even one product covered by Medicare or Medicaid, it must disclose all payments to doctors other than its own employees. The federal government will post the information on a public Web site.

The penalty for noncompliance could be $10,000 for failure to report. A company that knowingly fails to report payments could be subject to a $100,000 penalty for each violation, to a maximum of $1 million a year.

Comments about the proposal were accepted until Feb. 17, then Medicare officials were to issue final rules with the force of law.

Here’s where the archers among us start to take aim. As reported on FDA Law Blog, earlier this month the Centers for Medicare & Medicaid Services (CMS) announced “that manufacturers will not be required to collect data under the physician payment sunshine provisions of the Patient Protection and Affordable Care Act before Jan. 1, 2013.”

The regulation requires the first report to be submitted by March 31, 2013 for payments made in this calendar year, but CMS already has exceeded one deadline--under the Patient Protection and Affordable Care Act (ACA), payment-reporting procedures were supposed to be established by of Oct. 1, 2011.

The postponement gives CMS time to review more than 300 comments about the proposed rule, and also affords manufacturers additional time to prepare for the disclosure reports. Although the CMS didn’t expressly say the March deadline was extended, it’s implicit in the delay.

On news of the extension, Sen. Charles Grassley, R-Iowa, one of the sponsors of the Physician Payments Sunshine Act, said, “It’s disappointing that CMS won’t even collect data at all this year. The process has dragged on long past the statutory deadline for implementation. Consumers need to know more about the financial relationships between their doctors and drug companies sooner rather than later. It’s important that CMS get this right in every way, including the usefulness and accuracy of the information. Given all of the extra time, CMS will have no further excuses for not accomplishing these goals.”

We’d like to believe him. But when it comes to excuses in Washington, supply always
seems to exceed demand.

If you think the word “blockbuster” is reserved for popular entertainment like “Game of Thrones,” you probably don’t need to take a blood thinner. Such drugs are prescribed to people at risk of stroke from conditions such as atrial fibrillation (irregular, rapid heart rate).

In Pharma Land, the drug Pradaxa is considered a blockbuster, or a drug whose annual sales top $1 billion. It’s touted as superior to other anticoagulant drugs because it requires less monitoring.

But just as a blockbuster movie can be ravaged by critics, a blockbuster drug can collect seriously bad reviews.

Since its U.S. introduction in 2010 by Boehringer Ingelheim as an alternative to Coumadin (warfarin), Pradaxa has engendered hundreds of adverse event reports to the FDA, according to AboutLawsuits.com, concerning hemorrhages and internal bleeding. Lawsuits charging wrongful death have cited Institute for Safe Medication Practices (ISMP) records tallying scores of deaths from bleeding.

Other anticoagulants, such as Coumadin, also pose a risk of bleeding, but patients on warfarin can be given vitamin K as a fast-acting reversal agent to bleeding problems. Pradaxa lacks such an antidote to disaster.

Lawsuits also challenge the rigor with which Boehringer Ingelheim researched its drug and allege that the company promoted it as an alternative to the older, safer warfarin despite failing to warn about the lack of a reversal agent.

More incidents of uncontrollable bleeding with Pradaxa, according to the ISMP, were reported during the first quarter of 2011 than were reported for any other drug monitored by the institute. More than 500 reports were made about Pradaxa versus 176 for warfarin, which ranked second.

Researchers have suggested that Pradaxa drug trials were flawed, and the FDA is investigating the bleeding claims, as are agencies in Europe and Canada.

But if you’re Boehringer Ingleheim you don’t dare argue with success. The company recently boasted that the launch of Pradaxa was “among the most successful market introductions in the pharmaceutical industry in the past few years.”

Not if you’re a Pradaxa patient bleeding to death with no way to stop it.

Although the FDA still considers Pradaxa a worthy drug, it has recommended that Pradaxa patients immediately contact their doctor if they detect signs of bleeding problems. They are:

• unusual bleeding from the gums;


• frequent nose bleeds;


• unusually heavy menstrual or vaginal bleeding;


• severe, uncontrolled bleeding;


• pink or brown urine;


• red or black stool that looks like tar;


• unexplained bruises that grow over time;


• coughing up blood or blood clots; and/or


• vomiting blood or a substance that looks like coffee grounds.

Last year, a U.S. Supreme Court ruling prohibited injured patients from suing generic drug companies. Because such companies lacked control over the content of their labels, the court said, if they’re unable to print warnings about drug side effects, patients shouldn’t be able to sue them.

A previous Supreme Court decision allowed patients who took brand-name drugs to sue their manufacturers. Since the decision last year, cases have been thrown out in which patients claimed harm from taking generic drugs. But in many of those cases, the plaintiffs suffered the same injuries as people who took the brand-name versions.

Last week, companion bills were introduced in both houses of Congress to address the inconsistency.

“If a consumer takes the brand-name version of drug, she can sue the manufacturer for inadequate warnings,” said Sen. Patrick Leahy, D-VT, in a statement. “If the pharmacy happens to give her the generic version, she will not be able to seek compensation for her injuries,” he said.

The legislation, as reported by The New York Times, would permit generic drug companies to update warning information about the drugs they manufacture. That would enable patients to sue them if they failed to warn about the risks associated with their drugs.

If it seems like a no-brainer that what’s good for the goose is good for the gander, the outlook for passage isn’t exactly rosy: The Republican-controlled House is likely to vote thumbs-down.

Consumer groups have requested that the FDA take similar action, but the agency has demurred.

As The Times reported, generic drug companies have opposed the label content measure on the grounds that it could create chaos. What if several different drug companies publish conflicting warning information about the same drugs? Now, only brand-name drug companies may update the labels, including everything about a drug’s uses, dosages and risks. Then, generic manufacturers must follow suit.

You’d expect Big Pharma to wiggle away from accountability. Let’s hope Congress does the right thing.

Few medical conditions are as embarrassing as urinary incontinence, so no wonder that its victims often are desperate to try anything that might help. A new study in the Annals of Internal Medicine concludes that for many women, drugs are inadequate and can produce side effects that may be worse than the disorder.

As described in a story last week by Reuters Health, the medical journal reviewed 94 clinical trials that tested drugs for women’s “urge” incontinence—that’s the diagnosis for urine that leaks after experiencing a sudden, strong urge to urinate. It’s less common than “stress” incontinence, when urine leaks because of pressure on the bladder from coughing, lifting or exercise.

Drugs prescribed in the U.S. to treat urge incontinence include Toviaz (fesoterodine), Ditropan (oxybutynin), Vesicare (solifenacin), Detrol (tolterodine) and Sanctura (trospium). They mitigate the urge to urinate by relaxing the bladder. As the review showed, however, they do so only for a minority of women. Fesoterodine was the most effective, and tolterodine the least.

But incontinence was resolved for only 85 to 130 of every 1,000 women using the drugs. Most did not become continent, and 13 to 63 of every 1,000 stopped taking their medication because of side effects, which included dry mouth, constipation, blurred vision and dizziness.

The most troublesome drug for side effects was oxybutynin.

The study’s lead author, Dr. Tatyana Shamliyan of the University of Minnesota School of Public Health, said patients first should try lifestyle changes. If they don’t work, she told Reuters, medication “should be seen as a treatment option. But they are not magic pills."

One unknown is the long-term effect of taking drugs for incontinence. The trials under review in the Annals of Internal Medicine were only two to three months in duration.

The drugs range in cost from about $100 to more than $200 a month. The generic version of oxybutynin costs only about $10 a month.

Urinary incontinence is more common in women. It can be part of the gift that keeps on giving—vaginal childbirth is a major risk factor. Others are obesity and diabetes, the latter because it increases urine production and can cause nerve damage affecting the bladder.

A Reuters story last year noted that more than half of all women older than 20 had reported problems with urine leakage in the last year.

Shamliyan said first-line treatments should include:

• exercise and a healthful diet to maintain optimal weight;


• giving up cigarettes—nicotine can compromise bladder control;


• limiting the consumption of caffeine and alcohol, and not drinking much at night.

Other measures are described as “bladder training,” when patients follow a bathroom schedule even if they don’t feel the urge to urinate. Kegel exercises, which strengthen the pelvic muscles that control urination, also should be practiced daily. They’re simple—identify the relevant muscles by starting and stopping your stream of urination. Then, several times a day, practice flexing and relaxing these muscles, which you can do almost anywhere, and no one will notice.

Using what some observers might describe as systemic loopholes, Abbott Laboratories used lawsuits and minor reformulations of TriCor to hold off generic competition to its cholesterol- and triglyceride-lowering drug. We recently wrote about Eisai and Pfizer pulling the same stunt with its Alzheimer’s drug, Aricept.

The study, published in the Archives of Internal Medicine, estimated that the prolonged exclusivity of brand-name formulations of fenofibrate cost the U.S. health-care system approximately $700 million per year.

Sometimes, drug companies pay off potential competitors to buy extra time for their brands. That cost to consumers also is considerable.

As reported on MedPage Today, generic versions of fenofibrate have been available for more than a decade. When the generic product was developed, Abbott sued, alleging patent infringement. Such lawsuits, per FDA rules, require a 30-month delay in approval of the generic.

The interlude enabled Abbott to reformulate TriCor by slightly revising its dose and presenting the re-branded “Trilipix” (fenofibric acid) to the FDA as bio-equivalent to the original version. By the time Abbott had Trilipix on the market, pharmacists, by law, were unable to substitute a generic because of the dosing difference. Brand-name sales tripled from 2002 to 2009.

The researchers said that Abbott had used the delay tactics twice to protect TriCor from generic competition, and that the company had presented clinical trial results indicating that the reformulations were not more effective or safer. So in addition to higher expense, patients get the short end of this corporate-shenanigans stick for its diminished therapeutic value.

Last year, the FDA required Abbott to relabel Trilipix to reflect the trial results. The agency also ordered that a new clinical trial be conducted.

An editorial accompanying the research study acknowledged that Abbott’s gaming of the system was “perfectly legal,” but that the real news is that the company’s methods “"exposed many patients to a drug with high costs, known risks and little or no clinical benefit."

In addition to the always-possible allergic reaction, TriCor’s risks include rare but severe muscle or joint pain, headache, nausea, chest and stomach pain, confusion, irregular heartbeat, persistent sore throat, coughing up blood, skin problems, dizziness or lightheadedness, shortness of breath and unusual bruising or bleeding.

As readers of this blog know, Abbott is hardly alone in putting its financial interests ahead of medical need. To remedy the situation of Big Pharma fending off competition at significant cost to patients, the researchers suggest:

• allowing pharmacists to substitute bio-equivalent generic drugs, even if the dosing is different;


• requiring companies to seek approval for a dosing change to settle any patent infringement suits before approval, which would allow the generic and the new brand-name version to compete immediately;


• requiring companies to market such reformulations under different brand names.

Find out more about prescription drug reports from the FDA, and more basic information from Drugs.com.

A couple of months ago, we wrote about the overuse of antibiotics, and how the FDA had curbed use of some of them in livestock. The concern was that inappropriate use of antibiotics can encourage development of drug-resistant bacteria—the “what doesn’t kill you makes you stronger” scenario.

Last month, a federal judge ordered the FDA to step up its regulation of antibiotics for farm use. According to AboutLawsuits.com, he said that the agency must begin eliminating nonmedical use of penicillin and tetracycline on livestock.

The venerable bacteria-killers are administered in low doses to cattle, pigs and fowl not because the animals are ill, but to promote growth and protect against disease. Bad idea. Using antibiotics without presence of infection (and sometimes even when there is one) is unsafe for humans. It serves only to create superbugs, such as methicillin-resistant Staphylococcus aureus bacteria (MRSA). These bacteria are responsible for 6 in 10 hospital staph infections, and the Centers for Disease Control and Prevention (CDC) says 5,000 people die from them every year. Some experts put the total annual MRSA death toll at 20,000.

Estimates of antibiotics in farm animals are as high as 7 in 10 uses. In 1977 the FDA said it would begin limiting nontherapeutic use of these drugs, but failed to do in the livestock industry. Environmental and consumer advocates sued.

Now, pharmaceutical companies might be required to petition the FDA for approval before antibiotics may be used in animals, and must prove them to be safe for humans. Of course, the FDA may well appeal the ruling. The FDA Law Blog said it would be surprising if the agency doesn’t appeal, “given FDA’s likely view that it intrudes on the Agency’s ability to set regulatory priorities.”

The blog also said that if the decision isn’t appealed, or is affirmed on appeal, the precedent would invite other parties to pursue legal means to force the FDA to remove any particular drug product.

This issue isn’t over.

As the Supreme Court begins to grapple with the Constitutional challenges to the Obama administration’s health-care reform legislation known as the Patient Safety and Affordable Care Act (ACA), Republicans in the House of Representatives continue to object.

In the words of Fiscal Times correspondent Merrill Goozner, writing on his GoozNews blog, the GOP “took another swipe at the alleged rationing in Obamacare” when they voted to disband the Independent Payment Advisory Board (IPAB). Its purpose is to examine Medicare spending when it grows substantially faster than the economy, and to offer Congress options of how to rein it in. Congress may exercise its suggestions, or enact its own cost-control measures.

That’s a reasonable oversight responsibility for a panel of 15 experts designed to resist political pressure. But Republicans have used fear and loathing to mischaracterize it and, by extension, the rest of health-care reform. They called the IPAB a “death panel,” accusing it of rationing care for the elderly.

Neither party can claim success in moderating Medicare spending, and Goozner indicts the tone of the House debate over the IPAB as the “perennial obsession with the next election, not the next generation.”

The House vote is insignificant because the Senate won’t confirm eliminating the advisory panel, but, Goozner notes, there’s irony in the fact that the vote occurred only a day after a different advisory panel at the Centers for Medicare and Medicaid Services (CMS) convened to discuss coverage issues. That meeting illustrated how wise rationing could save both patients and the government billions of dollars a year without jeopardizing care.

We’ve addressed the issue of cost-effective, appropriate care, by no less a vested interest than the American College of Physicians. The CMS panel, Goozner reports, considered whether there was sufficient scientific evidence to support a Medicare decision to subsidize drug treatments for diabetic macular edema. Caused by diabetes, the disorder compromises vision and can cause blindness.

An expensive drug made by Roche/Genentech called Lucentis is under consideration by the FDA. It costs $1,624 for a monthly shot which diabetics would require for the rest of their lives. Another drug, also made by Roche/Genentech, called Avastin, is equally effective. It’s essentially the same drug, but it’s compounded in larger doses than the newer, pricier version, and was approved by the FDA as a cancer, not diabetes, treatment.

Eye doctors, as Goozner explains, understand that dividing Avastin into smaller doses appropriate for injection into the eye pencils out to $43 per treatment.

If Avastin sounds familiar, that’s because of its recent notoriety over serious side effects, and problems experienced when eye injections are performed improperly.

But that’s not Goozner’s focus here. He’s concerned that the 325,000 Medicare beneficiaries who have diabetic macular edema and might qualify for the treatments must pay 20 percent of the cost as a co-pay. That’s $324.80, every month, for Lucentis, versus $8.60 for Avastin. The seniors get burned, and so do taxpayers.

“If everyone on Medicare who is eligible for the treatment receives Lucentis, it will cost the government $6.3 billion a year,” Goozner says, according to a report submitted to the panel. “If they receive Avastin, the government will pay only $167.7 million.”

The CMS committee, by law, may not consider cost when evaluating whether or not to pay for a treatment. The reform law that Republicans are trying to repeal says comparative effectiveness research paid for by the government—research such as the assessment on diabetic macular edema—cannot be used in making payment decisions.

So the committee’s vote reflected only science, not cost. It decided that both drugs worked about the same.

Currently, both are being used “off-label,” that is, for a purpose other than what they were approved for by the FDA. Still, Medicare contractors in about half the states, Goozner reports, pay for them. Once the FDA approves Lucentis for diabetic macular edema, Roche/Genentech won’t submit an application for Avastin as a treatment because they’re concerned about profit, not price. By law, Medicare must pay for an FDA-approved drug. And doctors, who get a small piece of the price of drugs they use in their offices, will have an incentive to use the more expensive, approved drug.

So, explain to us, again, why the ACA’s Independent Payment Advisory Board should be eliminated?

If you wish to register your opinions on rational rationing or irrational non-rationing and their effect on the public and individual bottom line, contact your Congressional representatives. You can find them here, as well as Congressional leadership.

In some ways, Alzheimer’s is like arthritis. Its symptoms can wax and wane, making it difficult to determine if a particular treatment is successful. Who’s to say if a symptom subsided because a drug worked or because it was going to diminish anyway?

And, like arthritis, Alzheimer’s cannot be cured, only moderated. That can lead sufferers and the people who care for them to become desperate for any new treatment—what have they got to lose?

So dementia leaves its victims particularly vulnerable to new, if not improved, ways to treat it, and one such recent attempt raised the ire of two professors at Dartmouth’s Institute for Health Policy and Clinical Practice. As reported by Merrill Goozner, Drs. Lisa Schwartz and Steven Woloshin claim that the FDA has “breached [its] own regulatory standard” in approving a new dosage of a best-selling Alzheimer’s drug.

Aricept, whose generic name is donepezil, is earning its manufacturers $2 billion a year for improving memory lapses in the short term. With its patent about to expire (Aricept was introduced in 1996), and generic manufactures poised to compete with their own versions, manufacturers Eisai and Pfizer were motivated to keep the cash flowing. They appealed to the FDA to approve a higher dosage, claiming that a trial of 1,400 patients demonstrated improvements in the ability to think. The feds gave the drug makers three more years to market the stronger drug exclusively.

But as Schwartz and Woloshin wrote in the British Medical Journal (BMJ), patients had only slightly better cognition on the higher dose, and it had absolutely no effect on day-to-day functioning, the measure by which caregivers determine disease status. Unfortunately, the stronger Aricept conferred significantly negative side effects, including nausea and vomiting. For patients with dementia, that can lead to pneumonia. The FDA had told the trial sponsors that the drug wouldn’t be approved unless it had a positive impact that patient caregivers could notice.

So at best, the contrary approval makes the FDA look dysfunctional; at worst, it looks incompetent and corrupt.

Aricept’s manufacturers went merrily along their marketing way, their advertisements implying to consumers that the drug helped the Alzheimer brain function better, but not mentioning the severity of side effects. And the ads aimed at doctors, Schwartz and Woloshin charged, were worse: “[They contain] a stunningly erroneous statement in a large bold font: ‘Patients on Aricept 23 mg/day experienced important clinical benefit on both measures [cognition and overall functioning],’ which is simply not true. In fact, this statement is directly contradicted by a statement in a smaller plain font that says that the results for global function ‘did not show statistical significance.’”

That doctors are considered easy marks for Big Pharma is depressingly old news.

Unless drug company labels make inaccurate claims, the FDA does not intervene, even if a drug's risks, benefits and uncertainties aren't communicated.

As explained in the Los Angeles Times, drug companies commonly respond to an expiring patent with a practice called "evergreening." To prolong the profitability of successful drugs, they make a slight change to a drug's formula or dosage, or combine it with another drug. These are legal measures that require FDA approval.

Aricept’s new 23-milligram tablet, The Times story explained, “created a dose that couldn't be reproduced by any combination of Aricept's existing 5- and 10-milligram pills, making the product new enough to win a three-year reprieve from low-cost competitors.”

Dr. Howard Brody, a medical ethicist at the University of Texas Medical Branch in Galveston, told The Times that the Aricept 23 case is “a perfect storm” of commercial marketing and regulatory failure whose victims are patients who are desperate, discouraged and vulnerable.

As Dr. Marcia Angell, former editor of the New England Journal of Medicine, told the newspaper, Big Pharma’s manipulative ads illustrate “very well how drug companies exaggerate the benefits of their drugs, minimize the side effects and through misleading marketing to both doctors and the public convince them that a new version of a drug, with a new patent, is better than the old one, whose patent has expired."

If your loved one is prescribed Aricept for his or her Alzheimer’s disease, ask the doctor what is the dose. If it’s 23 milligrams, ask for a lower dosage. It’s just that simple.

First published on Technorati.

Off-label use of drugs—that is, taking medication to address a problem other than the one for which it was developed and approved by the FDA—is a common and often appropriate practice.

Unfortunately, off-label use is also commonly abused and sometimes dangerous. Among the more alarming off-label practices these days is taking antipsychotic drugs—those used to treat severe mental disabilities—for lesser problems such as insomnia.

As reported recently in the Washington Post in association with Kaiser Health News, until the last decade, an expensive class of drugs called atypical antipsychotics was reserved for only the 3 in 100 people suffering from the most disabling mental illnesses such as schizophrenia. The most popular—Seroquel, Zyprexa and Abilify—are being prescribed off-label for anxiety and attention deficit disorder. Shockingly, as The Post/KHN notes, “Two recent reports have found that youths in foster care, some less than a year old, are taking more psychotropic drugs than other children, including those with the severest forms of mental illness.”

We’ve addressed the overmedicating of children here and here, and the general misuse of depression drugs.

Pharmaceutical companies, of course, couldn’t be happier. Antipsychotics accounted for more than $16 billion in sales in 2010, and often sell better than meds that lower cholesterol. A Stanford studyfrom last year concluded that off-label antipsychotic prescriptions doubled between 1995 and 2008

Although manufacturers are not allowed by law to market drugs for off-label uses, nothing prevents physicians from prescribing them. Thanks, critics say, to hype—TV commercials promote these powerful drugs, which can cost $500 per month—many professionals believe that they are safer and that the newer drugs address more disorders than their predecessors.

Big Pharma has been so successful in encouraging this perception that it has been willing to pay, according the The Post, more than $2 billion in the last few years to settle lawsuits about illegal marketing. In 2009, Eli Lilly and Co. shelled out $1.4 billion to settle charges that it marketed Zyprexa to nursing homes, among other health-care providers, as a sleep aid. We wrote about another such settlement recently.

And consumers pay the price. As quoted by The Post/KHN, Dr. Allen Frances, former chair of psychiatry at Duke University School of Medicine, said, “Antipsychotics are overused, overpriced and oversold.” If some off-label use is appropriate for people for whom other treatments have not worked for, Frances called their widespread use promiscuous and reckless.

Why would anyone take a drug designed to moderate hallucinations and delusions solely to alleviate occasional anxiety when the side effects can include rapid weight gain of 40 pounds, Type 2 diabetes, breast development in boys, irreversible facial tics and an increased risk of death among elderly patients?

Taking these drugs to solve what can be deemed “problems of living” is like using a machete to slice apples. Doctors might find that a suitable way to make fruit salad, says Wayne Blackmon, a psychiatrist and attorney, because of the financial incentive to prescribe quick-fix drugs instead of taking the time to evaluate nondrug treatments. It’s also about insurance companies quick to subsidize pills but not behavioral therapy.

When military operations exceed their stated purpose, it’s known as mission creep. When doctors ascribe difficulty coping as mental illness, it’s diagnosis creep. And the proper response is not to medicate in hopes of moderating symptoms. It’s to re-evaluate the pressures on both patients and doctors to solve a problem via the path of least resistance instead of the more painstaking path of education and information.

If your doctor, particularly if he or she is not a psychiatrist, prescribes an antipsychotic medication for a disorder other than extreme mental illness, ask:

• what alternative treatments are available?


• what are the possible side effects?


• would you take this drug?

If you suffer a terrible injury from taking a generic prescription drug, you have no legal recourse. So ruled the U.S. Supreme Court last year in a case that divided along political lines with five conservative justices throwing a new lifeline of legal protection to the generic drug industry.

Now the consequences of that decision are being borne out as hundreds of patients injured by generic drugs are finding their lawsuits thrown out of court. Some of their stories are gathered by the New York Times in a new report on this arbitrary distinction between generic drugs without legal recourse but brand names where the injured consumer still can sue.

Since the Supreme Court's ruling is not based on the Constitution but just its own interpretation of the wording of the Food and Drug Act and the regulations of the Food and Drug Administration, either Congress or the FDA could fix this problem. But that means politics, and the powerful drug industry will fight hard to protect its advantages. Stay tuned to see if anything happens legislatively to reverse this unfair decision.

A class of drugs called statins lowers blood cholesterol levels by reducing the production of cholesterol by the liver. Lipid regulators, which are primarily statin drugs, are the most commonly prescribed medication in the U.S., according to a report by the IMS Institute for Healthcare Informatics.

Last month the FDA acknowledged that statins may play a role in elevated blood sugar, as well as memory and cognition problems. It determined that the increased risk of diabetes was sufficient to warrant a warning on statin labels.

Although cholesterol is essential to normal cellular function, it also contributes to the development of atherosclerosis, a condition in which cholesterol-containing plaques form within arteries. They can become blood clots and cause angina (chest pain) and heart attacks. If the clot occurs in the brain, the result is a stroke.

Statins are prescribed to prevent and treat atherosclerosis. The most common statin brands are Liptor, Lescol, Mevacor, Crestor, Socor and Pravacahol, among others. They can save lives, but, as always with prescription medicine, are not without risk.

Despite the additional warnings, according to a story by ABC News and MedPage Today, the FDA said it "continues to believe that the cardiovascular benefits of statins outweigh these small increased risks."

The agency backed away from an earlier recommendation that patients taking statins undergo routine liver function tests, but advised that their doctors order one before starting patients on statins. The FDA has determined that the risk of liver damage is rare, but unpredictable.

The diabetes warning is not surprising, given that one trial resulted in an increase of 27 percent in new onset of diabetes among patients taking statins. Those results were curious, because the study subjects were people without a history of cardiovascular disease—a so-called “healthy patient trial.”

At the time, the FDA approved the study drug (rosuvastatin) for prevention of cardiovascular problems, but the scientific community took note of its peripheral results.

Another study reported in the ABC/MedPage story, showed that hyperglycemia (elevated levels of blood sugar) occurred among patients taking atorvastatin, and analysis of 13 different statin trials yielded increased risk of diabetes in nearly 1 in 10 subjects.

The other concerns noted by the FDA were mostly the result of adverse event reports, which are made by patients, practitioners, pharmacists, etc., after a drug reaches the consumer market. The agency said they generally involved individuals older than 50 “who experienced notable, but ill-defined memory loss or impairment that was reversible upon discontinuation of statin therapy."

A few days after the diabetes/memory loss warning issued, the FDA said certain statins—atorvastatin (Lipitor), rosuvastatin (Crestor) and simvastatin (Zocor)—might prompt negative interactions in patients taking drugs to treat HIV/AIDS or hepatitis C. The agency issued a warning about those drugs, and reiterated its warning about combining lovastatin (Mevacor) with HIV and HCV drugs.

The potential problem here is kidney damage. If you take these drugs, consult your doctor immediately about lowering the dose or making other alterations.

Practitioners greeted the diabetes warning-label decision with mixed feelings. Although some expressed support for relaxing the liver function test, they were concerned that patients would be scared away from the statins they need to control their cholesterol.

"All drugs have side effects and rarely some patients will have an odd reaction to statins—cognitive effects are among those—and are usually mild and resolve with stopping the medication,” said Dr. Harlan Krumholz of Yale University.

Dr. Steven Nissen of the Cleveland Clinic said "these are reasonable and prudent recommendations. I am pleased that FDA did not overstate the diabetes and cognitive function risks. Both problems are uncommon and don't diminish the importance of statins in cardiovascular protection. For the vast majority of patients, the benefits far outweigh the risks."

If you take a statin drug, or are considering it, discuss potential side effects with your doctor. Ask him or her if you can try behavioral therapies—diet and exercise—first. We’re hardly alone in questioning whether statins are too often the go-to drug for practitioners. So if your doctor is unwilling to consider options, especially if you are not yet taking statins, it’s time to get a second opinion.

Merck can’t say it wasn’t warned.

In what the FDA Law Blog calls the first of its kind, the FDA last month sent the pharmaceutical manufacturer notification that it violated its promise to conduct postmarket research (PMR) on its diabetes drugs Januvia and Janumet.

The letter represents new authority Congress granted the FDA to compel the pharmaceutical industry to conduct followup studies to assure a drug’s long-term safety after problems have been reported. Violations of this obligation can result in charges of misbranding, and in fines of $250,000 and potentially more if they continue.

This is crucial to patient safety, because what many patients don't realize, but is openly acknowledged in the drug and device industry, is that the first few years a new product is on the market is a crucial test of how safe the new drug or device really is. And keeping track of bad events is really important, but scarcely done well in the United States, at least up to now.

The Merck drugs were approved in 2006 and 2007 respectively. The FDA’s Adverse Event Reporting System (AERS), an information database and postmarketing safety surveillance program for all approved drug and therapeutic biologic products, received reports of pancreatitis associated with the use of the drugs.

In 2009, the FDA recommended that doctors monitor patients for signs of pancreatitis (inflammation of the pancreas) after initiating treatment with Januvia or Janumet, or after increasing their dosage. The feds had found that 58 of 88 cases of pancreatitis in the drugs’ users required hospitalization, four in intensive care. And last year a study in the journal Gastroenterology found that Januvia might increase the risk of pancreatic cancer as well.

In light of the adverse events reported, Merck agreed to conduct PMRs via a three-month pancreatic safety study with rats. The final report was due last June.

But Merck’s study results were rejected because the FDA had not approved its design. The agency implied that the studies hadn’t reached sufficient levels of exposure to properly evaluate the safety concern.

The Warning Letter orders Merck to submit a plan for the study within 30 days of its issue. The trial must begin within six months of the agency’s approval of the plan.

The FDA was hardly demure in its Merck smack down: “You have not provided an adequate explanation for the cause of the delay of either of the milestones in the timetable for completion of the postmarketing requirement, nor did you propose to revise the agreed-upon timeline,” read a passage in the Warning Letter. “[Y]ou are more than 20 months late in achieving the June 15, 2010 final protocol submission milestone and more than 8 months late in achieving the final protocol submission milestone in the timetable, and you have not demonstrated good cause for these delays.”

The agency concluded that Merck’s drugs were misbranded, and threatened it with financial penalties and the wrath of “other federal agencies” that might consider Merck’s recalcitrance “when considering the award of contracts.”

When Big Pharma acts only in its own interests, ignoring that of the patients who consume its drugs, it appears the feds are more willing to treat it as the dangerous scofflaw it is. As the Law Blog reported, only days after the Warning Letter was issued last month, the FDA issued a Notice to Industry that read, “Once FDA notifies a drug sponsor of the need for a postmarketing study or clinical trial, the company is required to provide a timetable for completion, including study milestones, and periodic status reports on progress toward completion of the PMRs. If a company fails to comply with the timetable, FDA is authorized to take enforcement action against the company, unless the company can demonstrate good cause for the failures.”

Impressive expression of force. But given Congress’ generally weak-kneed submission to the medical industrial complex’s financial power, is there bite behind this bark? Merck hopes not. We hope so.

It’s as if they’re playing hokey-pokey over at the FDA.

The Endocrinologic and Metabolic Drugs Advisory Committee recently gave a thumbs-up to Qnexa fewer than two years after recommending against it. It’s the first time since 1999 that an advisory panel for the federal agency has approved a weight-loss drug.

The FDA doesn’t have to accept the panel’s advice, but usually does.

The side effects that prompted the initial rejection of Qnexa are still of concern, but experts believe that if the drug is used only by a certain segment of the obese population and if trials study its performance after approval, the benefits for that population supersede the risks.

Like all the expansive media coverage of the Qnexa announcement, MedPage Today reported that concern centers around the increased risk of an elevated heart rate and of birth defects, specifically oral clefts.

Cardiovascular issues arise because Qnexa contains phentermine, the second member of Fen-Phen (fenfluramine/phentermine), an obesity drug yanked from the market six months after its introduction in 1997 because it increased the risk of valvular heart disease, posed a risk for birth defects and compromised mental acuity.

The drug combines phentermine, an appetite suppressant, with topiramate, an anti-seizure medication that increases the feeling of having eaten enough. Both drugs already are FDA-approved.

FDA panelists reviewed three studies that were conducted after the first advisory committee review of Qnexa and concluded that they did not show an association of topiramate exposure and risk of major congenital malformations. They warned, however, that topiramate exposure in pregnancy was likely to be associated with increased incidence of oral clefts.

Vivus, manufacturer of Qnexa, agreed to develop a risk-mitigation strategy that provides:

• labeling that states the drug should be discontinued if the patient becomes pregnant;


• distribution of Qnexa only through 10 certified mail-order pharmacies that agree to train pharmacists in use of the drug and submit to internal audits;


• targeted education programs aimed at providers and patients, including a brochure on contraception and recommendations for monthly pregnancy testing;


• development of a pregnancy registry to track pregnancy outcomes.

For a long time, Primatene Mist was the go-to relief for asthma sufferers in the midst of an attack. Known as one of many “rescue inhalers,” Primatene was used during critical moments to deliver epinephrine that opened airways and enabled breathing.

But as of this year, Primatene, the only asthma inhaler that was available over-the-counter, was taken off the market.

The problem wasn’t Primatene’s drug safety or efficiency; it was the adverse effects its spray propellant had on the ozone layer. After its departure, many asthma patients felt cast adrift from the only relief they could get without a prescription. According to a story in the Los Angeles Times, lung doctors and asthma specialists said Primatene wasn’t a good option for asthma patients anyway.

Asthma, these experts believe, is controlled more effectively with prescription medication than any over-the-counter product. "Primatene Mist does not treat asthma — it treats symptoms that can come from asthma," Dr. Kyle Hogarth, medical director of the pulmonary rehabilitation program at the University of Chicago Medical Center, told the L.A. Times.

He said that treating only the symptoms of asthma ignores the fact that repeated attacks can damage the lungs permanently. So the best asthma care prevents attacks, it doesn’t just react to them. That requires daily medication, such as inhaled corticosteroids, which prevent inflammation in the airways. The use of rescue inhalers, Hogarth said, should be limited to twice weekly.

Some asthma patients use prescription inhalers whose active ingredient is albuterol instead of epinephrine, and is delivered via a different propellant. Like Primatene Mist, they're used at the onset of an attack only to relieve symptoms. But they require more priming, have a different cleaning regimen, taste different and offer a less powerful puff.

Armstrong Pharmaceuticals, which manufactures Primatene Mist, is developing its product with the more environmentally friendly propellant, but it will continue to use epinephrine as the active ingredient.

But what if you’re one of the estimated 3 million Primatene users who aren’t sure now what to do, especially if you lack insurance coverage or the financial means to get the more expensive prescription drugs?

Community health centers often have sliding-scale payment options for patients requiring diagnosis, treatment and follow-up care. Your doctor and pharmacist are resources for medication assistance as well, and you can find prescription drug coupons online if you search by the drug or manufacturer’s name. Large retailers such as Wal-Mart and Costco often offer deep drug discounts.

Many pharmaceutical companies also offer patient assistance programs. For more information about asthma and medication assistance programs, contact:

• the Allergy and Asthma Network/Mothers of Asthmatics;


• Partnership for Prescription Assistance, (888) 477-2669;


• RxHope[www.rxhope.com], (877) 267-0517.



Posted by Patrick A. Malone | Permalink | Email This Post

Posted In: Medications

All medications carry risks and potential side effects, but seldom does a pill do precisely the opposite of what it promises.

That’s why Pfizer recalled about 1 million Lo/Orval-28 and generic norgestrel birth control pills. Thanks to a packaging error, women who are taking the contraceptive risk getting pregnant.

As widely reported, the recall announcement Jan. 31 explained that some of the blister packs could contain the wrong number of pills, and that the tablets could be out of sequence.

Properly prepared packages contain 21 tablets with active ingredients, and seven with inert ingredients. Pfizer said some packages involved in the recall contained too many tablets with active ingredients, and some had too few. Although manufactured by Pfizer, the pills were distributed under the Akrimax RxProducts label.

If you use this product, notify your physician and return the tablets to the pharmacy.

For a full list of affected lot numbers, NDC number (National Drug Code) and expiration dates, consult the recall announcement. If you have questions, call Akrimax Medical Information at (877) 509-3935. If you believe you experienced an adverse event, contact the FDA MedWatch Adverse Event Reporting Program.

When patents expire on profitable brand-name prescription drugs, patients and their insurance companies usually both catch a break on the price as generic manufacturers move in with cheaper versions of the same drug. That's happening now with Lipitor, the most prescribed brand name drug in the U.S., but the usual rules on pricing may be broken.

Every day 3.5 million people take Lipitor to control cholesterol. Since its debut in 1997, Lipitor has lined the coffers of Pfizer to the tune of $81 billion. It’s the best-selling prescription drug ever, and its patent protection ended in November.

A few months ago we wrote about how pharmaceutical companies whose patents are expiring for prescription drugs sometimes go to great—and questionable—lengths to prevent other manufacturers from making a generic version that costs a lot less. So it seems counterintuitive that a member of Big Pharma would celebrate the end of a drug protection period by lowering its cost below that of a generic.

But that’s exactly what’s going on with Lipitor.

In order to maintain loyalty among those customers who otherwise might have a choice (depending on their health plan coverage) often driven by cost, Pfizer cut deals with insurers and pharmaceutical plan brokers to price Lipitor at or below the cost of generic competitors. The company has even lobbied patients directly to take Lipitor instead of other atorvastatin-based compounds.

As reported in the Los Angeles Times, “It was an unprecedented effort, but the motivation was clear: When a drug loses its patent protection, more than 80 percent of its prescription sales are replaced by generics within six months…”

Often, patients are forced by their insurance plans to switch to generics when their drugs go off patent. Often, the transition is smooth, but sometimes generics are metabolized differently from the brand, and patients and their doctors prefer the status quo. Sometimes the generic is equally or more effective, and patients welcome the opportunity to choose.

Although brand and generic drugs share the chemical or biological agent responsible for addressing the problem, the other ingredients in the compound can be different, and the body can react differently. That’s why all drugs with the same primary agent don’t always have the same effect.

So how does the Lipitor situation affect you? The L.A. Times provided an excellent primer for what you need to know in a time of drug transition that will affect millions of people.

Is atorvastatin as good as Lipitor?

Pharmacologists don’t anticipate trouble with atorvastatin; Lipitor may not be much different from other statins now sold as generics. Generic statins are just as good for 95 in 100 people. They include lovastatin (Mevacor), pravastatin (Pravachol) and simvastation (Zocor).

I have a prescription for atorvastatin, but I was given Lipitor. Why can't I get the generic?

Pfizer made a deal with your insurance companies and/or pharmacy benefit managers (PBMs). Usually, one drug maker gets exclusive rights to make the low-cost generic version of a medication for the first six months after it goes off patent. Then additional generic drug makers enter the market, prices drop more and demand for the brand-name drug withers.

To prevent that with Lipitor, Pfizer agreed to pay rebates to insurers and PBMs to eliminate the cost advantage of atorvastatin. So some companies offer only Lipitor.

Is that legal?
No laws that govern how generics enter the market have been broken, according to Erik Gordon, an attorney and professor at the University of Michigan's Ross School of Business. But Pfizer's actions do raise questions about whether antitrust laws, which aim to keep market competition fair, have been violated.

Pfizer, the biggest drug maker in the world, seems to be using its muscle to make deals with the aim of undercutting the sale of generic Lipitor and limiting consumers' access to it, Gordon told The Times.

What’s odd here is that although Big Pharma often uses rebates to woo PBMs and influence insurance plan coverage, Pfizer’s Lipitor rebates are helping to make a brand name less expensive than a generic. Usually rebates afford an advantage to one or two comparable drugs in the same therapeutic class.

Is it normal for drug companies to do this kind of thing?

Drug makers have a long history of using rebates to influence PBMs and insurance plans as they decide which medications to cover, said Timothy Wentworth, group president of employer accounts with Medco Health Solutions, a large pharmacy benefit manager. What makes this situation unusual is that Pfizer's rebates are helping to make a brand-name drug cost less than a generic. Normally, rebates give an edge to one of two comparable drugs in the same therapeutic class.

Dave Marley, president and founder of the advocacy group Pharmacists United for Truth and Transparency. Marley said this practice is longstanding and prompted insurers including Cigna, Community Care Rx, Coventry and AARP to reject generic prescriptions for brand-name drugs, including Zyprexa (for schizophrenia and bipolar disorder), Nitro-Dur (to prevent chest pain) and Protonix (for gastroesophageal reflux disease, or GERD).

What else is Pfizer doing to keep patients on Lipitor?

The company offers discounts to patients through its Lipitor for You program, bringing the drug's monthly co-pay to as little as $4. Pfizer pays as much as $50 to cover the difference between the $4 minimum and a patient's usual co-pay for a preferred brand-name drug, which averages $25.

Enroll in Lipitor for You by linking here. Select "For Lipitor Patients" and click on "Lipitor for You." Or call (866) 354-7486. The deal is supposed to be good through the end of 2012.

What if I don't have health insurance?

Buy atorvastatin. Prices vary by pharmacy, but a 30-day supply of 20-milligram pills ranges from $80 to $130. Uninsured patients may take part in Lipitor for You and save $50 on the brand-name drug. At a cost of approximately $165 a month for a 30-day supply of either 20 mg or 40 mg pills, that might make Lipitor the less expensive option.

I don't want Lipitor. Can I get the generic?

It depends on the arrangements your insurance company has made. Some say they cover both Lipitor and atorvastatin. But Lipitor costs less for members at the pharmacy. Some insurers declined to participate in Pfizer's rebate program and require most members to switch to the generic. Some insurers will continue allow Lipitor at the cost of the generic co-pay for their Medicare patient.

If my generic prescription is filled with brand-name Lipitor, does that mean I'll pay more?

Not if your insurer has cut a deal with Pfizer; you'll pay the generic co-pay, about $10 for a 30-day supply, on average. For many patients, that's a price cut. And you might be able to lower the cost further via Lipitor for You.

What if I'm on Medicare?

Several pharmacy benefit managers and health plans say they'll continue to dispense brand-name Lipitor but charge a generic co-pay to people with a Medicare Part D prescription drug plan.

But you might pay more in the long run. People with Part D plans hit the so-called “doughnut hole” after accumulating $2,930 in drug costs this year; after that, their drug costs rise. When these patients get Lipitor, the drug's full cost is added to their tally, not the generic. So even with an immediately discounted co-pay, they reach the doughnut hole faster.

Medicare Part D plans are supposed to report rebates they get from drug makers to the government so that the Medicare program and its beneficiaries see cost savings as well. But a report last year by the Office of the Inspector General reviewed some Part D plan sponsors that received rebates when they encouraged patients to use certain drugs. It found that some plans passed along the rebate money and some didn’t.

Article first published as New Questions and Answers on Lipitor, the Most Prescribed Brand Name Drug in America on Technorati.

Given our propensity to pop an antibiotic at the first sign of a sniffle—and much of the medical establishment’s willingness to gratify this often unwise habit—it’s hard to believe that the use of antibiotics to fight infection has been common practice for only a couple of generations.

Like all medications, they come with risks of side effects, but in the right circumstances, antibiotics are truly wonder drugs. They’re so wonderful, however, that we overuse them. The problem then becomes not just one of risky and/or unpleasant side effects, but of reduced efficacy.

The more frequently antibiotics are used, the better bacteria become at resisting them. It’s simple evolution—survival of the fittest bacteria. The fitter (stronger) the bacteria, the more compromised the antibiotics. In order to keep up with the demand of increasingly resistant bacteria, new compounds must constantly be developed. The old ones simply don’t work anymore.

Antibiotic resistance occurs when humans ingest the drugs more frequently and for disorders they are not meant to address. But one contributor to this diminishing-effects scenario is not the direct result of human behavior—it results from the routine use of antibiotics in agriculture. They’re given to livestock to prevent disease and promote growth. That practice has been called into question often in recent years.

As explained in the Los Angeles Times, last year, the American Medical Association (AMA), the World Health Organization (WHO) and other medical groups warned that “the misuse of antibiotics in food animal production may be creating a serious problem for human health by fostering development of drug-resistant bacteria."

Further, some studies showed that taking antibiotics out of animal feed "made antibiotic-resistant bacteria less prevalent in both animals and people with no ill effects for animals or ranchers."

Earlier this month, the FDA put its foot down on some unapproved uses of antibiotics for livestock. The agency prohibited use in certain animals of one class of antibiotics called cephalosporins, and prohibited using the drugs for purposes other than their original intent (called “off-label” or “extra-label” use) except for animals that are rarely consumed by humans.

It wasn’t the first time the FDA attempted to curb the use of antibiotics in animals. In 2008, the FDA made a move to limit off-label antibiotic use in livestock, but wussed out in the face of opposition by agricultural interests.

Congressional Rep. Louise Slaughter (D-N.Y.) is a microbiologist who has written legislation addressing antibiotic overuse. In a statement about the latest action, she said, "We need to start acting with the swiftness and decisiveness this problem deserves. With over 1 million Salmonella cases in the U.S. each year, at least 30,000 Americans will contract cephalosporin-resistant bacteria every year. I'm glad the FDA is finally acting but how many Americans have needlessly been sickened in the meantime?"

The new rules take effect April 5, but as in 2008, there’s a comment period in the interim. Comments received last time helped sway the FDA against enforcing the restrictions. So if you care about antibiotic resistance, you might want to weigh in about the latest proposal. Link here to read a Q&A about general antibiotic use in animals and specifically this action. To submit comments, link here and include the docket number FDA-2008-N-0326.

A recently introduced bill in the House of Representatives seeks to update legislation for “orphan” diseases and drugs. “Orphan” status denotes disorders that are extremely rare—generally afflicting 6,000 or fewer patients.

Pharmaceutical companies have no financial incentive to develop drugs and treatments for them because there aren’t enough users to pay the costs and sustain the consumer market. In order to encourage the development of drugs and other treatments for orphan diseases, the government provides incentives it doesn’t grant to more common disorders, such as easier and faster FDA approval, and extended periods for developing companies to market the drugs exclusively.

Another advantage lawmakers hope to grant to orphan drug development is the routine use of a “surrogate endpoint.” Before drugs are given FDA approval, generally they must pass rigorous clinical muster; they must be tested in studies that identify the risks and side effects as well as the benefits of the treatment using meaningful numbers of real subjects. A surrogate endpoint substitutes for a real, observable, provable clinical result—the surrogate endpoint doesn’t necessarily have a guaranteed relationship with a clinical result like actual cure or extension of life, but it has a “biomarker,” according to the National Institutes of Health, that researchers can accept as indicative of clinical benefit, harm or the lack thereof.

Surrogate markers are used if the number of subjects that might be suitable for a clinical trial is so small that it wouldn’t result in a statistically significant result. It would be impractical to conduct a clinical trial in such circumstances, but the people who suffer—the people stricken with an orphan disease—still need treatment, so the surrogate endpoint, the more relaxed standard, is critical to their well-being.

The proposed law is called the Unlocking Lifesaving Treatments for Rare-Diseases Act, or ULTRA. Specifically, according to the FDA Law Blog, it would permit the FDA to approve an application for a drug designated both as an orphan drug and as a fast-track product by allowing the surrogate endpoint standard.

Currently, the FDA is able to “fast track” approval for a product that addresses a serious or life-threatening illness, and when it provides a meaningful therapeutic benefit to patients beyond the existing treatments.

If a product meets the criteria, the FDA may grant marketing approval based on a demonstrated effect on a surrogate endpoint reasonably likely to predict clinical benefit. Also, the manufacturer must commit to completing studies after marketing approval that confirm its benefits.

Last month we wrote about an executive order that renewed attention to the problem of drug shortages and the FDA’s inability to fix them. This month, both the Government Accountability Office (GAO) and a U.S. Senate Committee provided more ammunition for granting greater authority for the FDA to address the problem. There’s no real news, but there are more and louder authoritative voices to prompt positive change.

As recounted on FDA Law Blog, Marcia Crosse, GAO Director of Health, told the Senate Committee on Health, Education, Labor and Pensions that the FDA is “constrained in its ability to protect the public health from the impact of [drug] shortages.”

Bills in both the Senate and House of Representatives, and an FDA interim rule to enable the agency to
improve its collection and distribution of drug shortage information to physician and
patient organizations and to work with manufacturers to respond
to potential drug shortages speak to the government’s interest in solving the problem.

And, the pharmaceutical industry is beginning to step up. The Generic Pharmaceutical Association (GPhA) announced its own Accelerated Recovery Initiative to “reverse current drug shortages and prevent further ones. . . .”

Specifically, the industry initiative calls for:

• an independent third party to gather current and future supply information from stakeholders for products identified as meeting the critical criteria;


• that information to be used to determine current and potential supply gaps, with a focus on those products where a shortage is expected to last longer than 90 days; and


• a high-level SWAT team to be formed within FDA with the ability to quickly respond to critical shortages and work with the current Drug Shortage staff expanded through the president’s drug shortage initiative.

The GAO confirmed much of what everybody already knew or suspected. Between 2006 and 2011:

• Drug shortages have increased by 200 percent.


• The average duration of a drug shortage has been approximately nine months.

The GAO analyzed the causes of 15 drug shortages that had a significant impact on public health. Twelve out of the 15 shortages were caused primarily by manufacturing problems. Other factors contributed, such as having to make lengthy improvements to aging facilities and disruptions in the supply of certain drug ingredients.

Also, some drugs are produced by only a few manufacturers, so if one experiences manufacturing problems or supply-chain issues, there aren’t a lot of options to boost production elsewhere.

As noted, these issues aren’t news, nor the fact that even if the FDA knows in advance about drug shortages, it can’t resolve problems unless it has the muscle—the statutory authority—to require manufacturers to do what’s necessary to prevent, mitigate or end shortages.

As FDA Law Blog summarizes, the interim rule may significantly increase the instances in which sole manufacturers are required to notify FDA of an impending production disturbance. But without action by Congress, the FDA can’t expand the shortage reporting requirements, and will remain, as the GAO indicates, “constrained” with regard to drug shortages.

Another chapter in the book of “Big Pharma Behaving Badly” is being written, courtesy of a story by Bloomberg News. The news service obtained Bayer company emails reportedly showing executives discussing ways to illegally promote a long-controversial drug.

The suspect drug, Yaz, is a member of the family of birth control pills knows as Yasmin, which several studies suggest carry elevated risks for blood clots, and, possibly, pulmonary embolism, deep vein thrombosis and other life-threatening injuries. As noted on AboutLawsuits.com, an FDA advisory committee is supposed to review the data about the risks of Yaz and Yasmin next month.

The Bloomberg report charges that Bayer may have sought to market the birth-control pills for unapproved—or “off-label”—uses, misleading women about the health risks the drug posed. Specifically, Bayer is alleged to have discussed promoting the contraceptive Yaz to treat several types of premenstrual syndrome (PMS). The FDA has approved Yaz only for the most severe form of PMS.

Doctors are not prohibited from prescribing drugs for off-label uses, but manufacturers are not allowed to promote their drugs for any use other than what the FDA has approved. Earlier this month, we wrote about a large legal settlement paid by GlaxoSmithKline over its off-label marketing of a diabetes drug.

In the Bayer emails, a consultant allegedly suggested how the company’s sales representatives could converse with doctors in a way that invites them to conclude that Yaz is suitable for off-label use: asking doctors, for example, what percentage of their patients had common PMS symptoms, then asking what effect they thought Yaz might have on those situations.

An even bolder, in-your-face repudiation of federal law reflected in another email supposedly came from an executive promising that a doctor under contract to a Bayer unit would promote off-label use of Yasmin on the “Today” show.

According to AboutLawsuits.com, the FDA has warned Bayer at least three times in recent years about problems with Yasmin or Yaz advertisements. Bayer has been busted for its misleading ads overstating the efficacy and benefits, and minimizing the risks of Yaz and Yasmin.

“In 2009, Bayer was forced to run a $20 million corrective advertising campaign to address problems with Yaz advertisements that stressed the potential benefits in treating acne and symptoms of PMS, while minimizing the potential risk of blood clots and other side effects of Yaz,” the website reports.

As additional punishment for its loathsome marketing behavior, Bayer must get any U.S. advertisements for Yaz approved in advance by the FDA.

The legal process of suing someone or some organization involves “discovery,” in which both sides look for evidence from each other supporting their arguments. The Bayer emails were unearthed during the discovery process in numerous lawsuits involving Yaz and Yasmin filed against Bayer by women who took the medicine and suffered blood clots, strokes and gallbladder problems.

If a product is so great, why does its manufacturer have to bypass law and common decency to spread the word?

As the saying goes, keep your friends close and your enemies closer.

Not that we know for sure that behavioral economist Dan Ariely considers pharmaceutical manufacturers “enemies,” but we know he’s onto their practices that are not exactly in the best interest of patients. He and a colleague recently had dinner with a few pharmaceutical sales representatives to find out the tricks of their trade, which is getting doctors to prescribe their companies’ drugs.

Trick No. 1: “One of [the reps] told us a story about how he was once trying to persuade a reluctant female physician to attend a seminar about a medication he was promoting. After a bit of schmoozing, she finally decided to attend – but only after he agreed to escort her to a ballroom dancing class.” A fine example of, Ariely says, if-you-scratch-my-back-I’ll-scratch-yours.

Trick No. 2: “[B]ring meals to the doctor’s office. … [O]ne office even required alternating days of steak or lobster for lunch in exchange for access to the well-fed doctors.”

Trick No. 3: “When the reps were in the physician’s office, they were sometimes called into the examination room (as ‘experts’) to inform the patients about the drug directly. And the device reps experienced a surprisingly intimate level of involvement in patient care, often selling medical devices in the operating room, while the surgery was going on.” (Comment by Patrick Malone: What's really shocking is that these sales reps have at most a bachelor's degree and a few weeks of training from their employers.)

So, Ariely asks, what should be done about this shocking insinuation of commerce into medicine? “[R]ealize that doctors have conflicts of interest. …[P]lace barriers that will prevent this kind of schmoozing, and keep reps from accessing doctors or patients.”

And have dinner with somebody else.

Last week, GlaxoSmithKline agreed to pay $3 billion to settle several lawsuits over how it creates and markets drugs. It’s not as if anybody needed any more evidence that Big Pharma is an industry desperately in need of watch-dogging, but, from the Reuters report, here's the money quote: "… payments would be funded through existing cash resources."

Who except Lindsay Lohan has $3 billion lying around to pay off their bad behavior?

The settlement relates to several cases filed by the U.S. government, including those related to Avandia, Glaxo’s diabetes drug that has been linked to heart risks; how the company exploited Medicaid to boost drug sales profits; and allegations that Glaxo persuaded doctors to prescribe drugs for uses not approved by the FDA (a practice known as off-label marketing).

The United States has beefed up efforts to address unfair pharmaceutical industry practices. Since 2000, Reuters says, the number of industry settlements with state and federal entities has soared. The government is finally objecting to how pharmaceutical business as usual elevates profits over the interests of patients.

Sales reps often receive bonuses based on reaching target numbers, a practice that encourages off-label promotion, which can result in serious harm to patients.

As reported on the business radio program Marketplace, the government allows doctors the freedom to prescribe as they see fit, but it does not allow sales reps to say anything they want to about the drug.

Pharmaceutical companies are challenging that ban in court, claiming that what sales reps say is a form of free speech and should be protected. The Supreme Court recently ruled that some drug marketing is free-speech protected. And a case now in the federal Court of Appeals could decide whether that protection extends to off-label marketing. Which would mean even larger “cash resources” for Big Pharma.

According to Reuters, Glaxo has promised that it will behave in the future – Chief Executive Andrew Witty said that the settled cases "do not reflect the company that we are today."

Maybe.

But don’t forget that last year Glaxo paid $2.4 billion over patient liability claims relating to Avandia, for an investigation into its former Puerto Rico factory and for anti-trust and product liability litigation over Paxil, an antidepressant.

The whole industry’s character has long been called into question. Several other leading drug manufacturers, Reuters said, have settled U.S. charges for huge amounts, or have been forced to pay significant sums in anticipation of such deals.

• Last month, Abbott Laboratories accepted a $1.4 billion charge in conjunction with a U.S. federal investigation into marketing Depakote, an anticonvulsant drug.


• In 2009, Pfizer shelled out $2.3 billion for marketing Bextra (an arthritis drug that has been withdrawn) and other medicines for unapproved uses.


• In 2009, Eli Lilly cut a check for $1.4 billion after charges were leveled about the improper marketing of Zyprexa, an antipsychotic, for children and elderly patients.

Last week’s executive order was the first one in more than 25 years directly affecting FDA operations. That in itself speaks to the gravity of the issue it addresses: shortages of drugs, many of them life-saving.

President Obama’s order had two clear messages:
1. Drug shortages are too critical to ignore.
2. Congress has been derelict in resolving them.

As reported on FDA Law Blog, the number of prescription drug shortages nearly tripled between 2005 and 2010. Among the missing medicines are treatments for child leukemia, breast cancer, colon cancer, anesthetics and antibiotics.

If there isn’t enough medicine to treat everyone who needs it, doctors have to ration. Only patients in the worst circumstances get drugs and others either do without or receive a decidedly second choice. If there even is one.

And when someone must switch medicines in the middle of a course of treatment, the potential for reduced effectiveness is high.

The situation affects not only patient health and survival, it feeds a vicious cycle. Drug shortages create higher prices. They also can delay clinical trials for new, experimental treatments if the “control” group (subjects who are testing the standard treatment in comparison to the new one) is assigned to receive the absent drug.

The causes of drug shortages are many. The FDA has identified “quality/manufacturing issues,” production delays and the discontinuation of older drugs that don’t bring as much profit to their manufacturers as they used to.

Free-marketers say prices of older drugs are low until supply runs low. Industry officials say even the higher prices those drugs would bring if more were manufactured aren’t enough to offset the cost of slicing through the government red tape to increase production.

Once again, Big Pharma’s lust for profit compromises human health.

Congress introduced legislation earlier this year to expand FDA authority to require advance notice of impending drug discontinuations and notice of any circumstances that might cause a drug to be discontinued or its production impeded. But the legislation is languishing in committee, so Obama said, essentially, “enough.”

The executive order directs the FDA to:

• require sole-source drug manufacturers to notify the agency in advance of discontinuation that could lead to shortages of certain critical drugs;


• expedite reviews of new drug suppliers, manufacturing facilities and manufacturing changes if such reviews would avoid or mitigate existing or potential shortages;


• report drug stockpiling and price-gouging for scarce drugs to the U.S. Department of Justice.

Last week, the Federal Trade Commission (FTC) released a report with the boring title “Agreements Filed with the Federal Trade Commission under the Medicare Prescription Drug, Improvement and Modernization Act of 2003.”

But the story it tells is hardly dull, and it has implications for anyone who takes prescription medicine. If you want to read the whole report, spoiler alert! It concludes “pharmaceutical companies continued a recent anticompetitive trend of paying potential generic rivals to delay the introduction of lower-cost prescription drug alternatives for American consumers.”

The Washington Post was less than impressed with Big Pharma’s “pay-for-delay settlements.” As analyzed by FDA Law Blog, there were 43 more of these unsavory brand/generic settlements in fiscal year 2011 than 2010; 28 final settlements involved 25 different branded Big Pharma drugs that both compensated the generic manufacturer and restricted it from marketing the less expensive version of the brand med.

In 2004, the FTC didn’t find a single settlement in a patent litigation matter involving drug makers that raised pay-for-delay concerns.

The commission concluded that fiscal year 2011 “witnessed the continued trends of (a) record numbers of brands and generics resolving patent litigation prior to a final court decision on the merits and (b) significant numbers of such settlements potentially involving pay-for-delay.”

It seems obvious that, as The Post notes, “Such pay-for-delay arrangements hurt consumers and increase costs for federal programs such as Medicare and Medicaid,” but the Generic Pharmaceutical Association (“GPhA”) disagrees. It said that “the FTC continues to miss the fundamental point: Patent settlements speed up the availability of less costly generic drugs and save money for everyone; banning settlements and forcing drugs makers to continue lengthy litigation with uncertain outcomes will be costly.”

It’s saying that when generic companies litigate drug patent cases to conclusion (as opposed to settling the case earlier), the generic drugs are delayed from entering the market at least until the brand patent expires.

This expensive, consumer-averse mess would be eliminated by enacting the Preserve Access to Affordable Generics Act. It would effectively ban patent settlement agreements and empower the FTC to challenge suspicious deals. It would accept certain deals if “clear and convincing evidence” supports the notion that the “pro-competitive benefits outweigh the anti-competitive harms.” The nonpartisan Congressional Budget Office estimates that the government would save $3 billion over 10 years by eliminating pay-for-delay deals.

The FTC and the Obama administration have urged the Joint Select Committee on Deficit Reduction (the “super committee” charged with trying to find federal budgets cuts by the end of November) to include the legislation in its deficit reduction plan.

You wonder if all the zealots keen to limit patients’ right by unreasonably capping medical malpractice awards (euphemistically referred to as “tort reform”) are as eager to put a stop to what looks awfully like pharmaceutical company collusion.

The problems with the cancer drug Avastin are never ending. The FDA has issued a another warning about the drug’s dangers, this time involving ovarian failure, jaw necrosis (bone decay), blot clots and excessive bleeding.

We’ve written about Avastin as well, most recently last week in regard to its use as an injectable drug for macular dengeration, and about the risks it poses for breast cancer patients.

To explore just one of the reasons for the new warning, consider a study that found that 34% of women treated with Avastin during chemotherapy suffered ovarian failure, and most have not recovered their full fertility; only 2% given chemotherapy alone experienced ovarian failure.

Avastin was approved by the FDA in 2004 to treat nonsmall cell lung cancer and colorectal cancer in combination with chemotherapy. It received approval in 2008 to treat breast cancer, but that was revoked in 2010, and reconfirmed in June of this year.

When used for its original purpose, Avastin’s side effects can include high blood pressure, heart attacks, heart failure and the development of holes in the nose, stomach and intestines. All drugs carry the risk of side effects. Sometimes, they’re worth it. Increasingly, expanded use indicates that that’s not the case with Avastin.

The headline is no joke. It's what experts think is the explanation behind vision-ruining infections in the eye that happen occasionally with injections into the eye of a drug used to halt the progress of macular degeneration.

As the thinking goes, if the doctor is talking during the time he or she is drawing the drug from the vial into the syringe, tiny droplets of the doctor's saliva can then be transmitted into the patient's eye.

Another cause of eye infections in patients who get these injections is less than sterile conditions in the pharmacies that take a single vial of the drug and divide it up into the tiny doses for individual eye patients.

Whatever the cause, the infections known as endophthalmitis happen in about 1 in 1,000 injections of both of the commonly used drugs for the wet form of macular degeneration: Avastin (also used in cancer treatment) and the far more expensive Lucentis.

Read this New York Times piece for more on the subject, and about how a raft of publicized cases of infections with Avastin seems to be driving much of the eye injection business to Lucentis despite its higher price -- $2,000 a dose compared to only $50 a dose for Avastin.

A few widely used drugs once again are coming under fire, one thanks to the FDA and the other class courtesy of a consumer watchdog organization.

High doses of Celexa, an antidepressant, can cause abnormal heart rhythms, prompting the feds to issue a new warning that it should not be prescribed at doses higher than 40 mg per day. Disrupting the heart’s regular electrical activity can be serious and potentially fatal. Celexa packaging will now include a safety warning.

Available as a brand-name or generic drug, Celexa belongs to the class of antidepressants called selective serotonin reuptake inhibitors (SSRIs), which have been shown to be effective in treating major depression. Doses greater than 40 mg, the FDA says, are not of greater benefit. Sometimes Celexa is prescribed for other psychological disorders, a practice known as “off-label” treatment, so there is no “proper” dosage for such uses.

Patients with low potassium and magnesium are at increased risk of the serious heart problems from Celexa, says the FDA. Talk to your doctor if you have been prescribed a daily dose of more than 40mg. If you have experienced irregular heartbeat, shortness of breath, dizziness or fainting while taking this drug, contact your doctor immediately.

Public Citizen has raised the flag of concern about a class of drugs called proton pump inhibitors (PPIs). The organization wants the FDA to require a "black box" warning on labels for Nexium, Prilosec, Prevacid, Protonix and similar drugs prescribed for acid reflux.

The “black box” is the FDA’s strongest label warning, and is so named because it’s featured prominently and encircled by a black box.

Public Citizen says proton pump inhibitors, which are also widely prescribed for off-label uses, pose a risk of long-term dependence and other dangerous side effects such as an increased risk of bone fractures, infections, diarrhea and magnesium deficiency leading to heart problems.

In May 2010, the FDA did issue a warning about the risk of bone fractures from heartburn drugs, and updated it in March 2011, indicating that the risk appears to be linked to high doses of the medications used over a long period of time.

According to Public Citizen, acid reflux drugs were prescribed more than 119 million times in 2009 and generated sales in the United States of $13.6 billion. One in 20 people in the developed world take a PPI to reduce the production of stomach acid. If you’re one, now is the time to review your use with your doctor.

Anyone who watches TV has been bewildered/amused/confused/annoyed by pharmaceutical ads that begin by explaining how your life can be perfect if you take this drug, and end with a rushed recitation of all the things that can go wrong if in fact you do take the drug.

Drug companies, of course, are obliged by the FDA to include potential side effects when they’re trying to sell you their products. But as proved by a recent study in PLoS ONE (a journal for peer-reviewed scientific and medical research), Big Pharma pretty much thumbs its nose at the FDA when it advertises in medical journals, where it's trying to sell its wares to doctors.

Among the nine publications reviewed by researchers were such mainstream journals as Annals of Internal Medicine, New England Journal of Medicine and Journal of the American Medical Association. About half of the ads reviewed violated at least one FDA rule, and about one-third were “possibly” out of compliance because of missing information. More than half of the drug ads failed to quantify serious risks. Fewer than 1 in 5 adhered to all FDA guidelines.

As explained by MedPage Today, the pharmaceutical industry spends $58 billion on marketing; the FDA’s division of marketing and advertising has $9 million. So what are the chances a miscreant marketer will get caught?

To help bridge the budget gap, the FDA recently implemented the “Bad Ad” program, asking physicians to report nonadherent or misleading ads. But that’s like asking the playground monitor to report bad behavior – what’s bad to one monitor is just kids being kids to another. As the researchers noted, the guidelines are difficult to enforce, don't emphasize transparency and ignore basic information relevant to prescribing.

The most common breaches or possible breaches of rules were:

• misused references to the scientific literature;


• misleading use of graphics;


• failure to cite references;


• overrepresentation of the experience with the drug.

By medical specialty, at least one FDA rule was broken by ads for:

• 6 in 10 hematology/oncology products;


• 5 in 10 cardiovascular and diabetes products;


• more than 4 in 10 psychiatric products.

As the researchers wrote, “Advertisements do a poor job of conveying basic information necessary for safe prescribing, with the majority failing to quantify serious risks.”

Despite their concerns, they said that “most advertisements we reviewed satisfied the majority of FDA guidelines.” It makes you wonder, though, about the squishy nature of the guidelines – the researchers also noted that an ad that makes no specific claim about efficacy and does not quantify drug safety is still in compliance.

The study recommends that the FDA update and simplify ad regulations, and require ads to explain risks clearly, offer information on absolute benefits and verifiable references and identify the appropriate population for the drug’s use.

All of that seems like a no-brainer. And another reason why, when your doctor prescribes a drug, you should ask what are the potential side effects and risks, and why he or she has chosen it over others. Read the patient information that’s included in the drug packaging.

In 1999, the FDA approved the drug Actos for Type 2 diabetes. Its popularity grew substantially after its primary competitor, Avandia, was linked to increased risk of heart attack. In 2010, the drug generated $3.4 billion in sales for its manufacturer, Takeda Pharmaceuticals.

Now, Actos is under fire, too.

The drug was recalled this summer in France and Germany in the wake of increased incidents of bladder cancer among people who took Actos. Similar reports have occurred in the U.S., where the FDA has allowed the drug to remain on the market provided warning labels are added to the packaging.

Earlier this month, the first lawsuits over Actos’ alleged role in bladder cancer were filed in the U.S., and many more are expected to be forthcoming. The lawsuits charge that Takeda failed to disclose data showing an increased bladder cancer risk.

If you are a diabetic who takes this drug, notify your doctor immediately if you develop:

• blood in your urine;


• an urgent need to urinate;


• pain during urination; or


• pain in the back of lower abdomen.

“The consensus,” he said, “already is that (Actos) should only be considered ... after patients have exhausted all other options."

The U.S. faces a growing shortage of the low-profit but vital generic drugs that cancer patients and other desperate folks rely on. These drugs are made in places like India and China in plants that the Food and Drug Administration lacks power to inspect.

Meantime, Big Pharma focuses on new high-profit but low-benefit drugs. The latest examples of new FDA approvals: Provenge, a drug for prostate cancer which on average extends life by four months at a cost of $93,000, and Yervoy, a melanoma drug with a price tag of $120,000 for a similar average benefit of four more months of life.

As reported by Gardiner Harris in the New York Times, a lot of solutions are being proposed to the crisis that has been brewing for the last few years, ranging from creation of a government stockpile of drugs to a requirement that drug makers give an early warning to the FDA of inability to keep up with demand for drugs.

Good luck getting any of these passed by a Congress whose loudest members reflexively say the government is the problem, not the solution. But as many Times readers noted in comments on the new article, this story is another example of why we need smart government, not no government, to address the many failures of the free market when it comes to vital services like health care.

As reported in the journal Health Affairs, antidepressant drugs are the third most commonly prescribed class of medications in the U.S. Much of the growth of these drugs has been fueled by prescriptions written by nonpsychiatrist caregivers, and are not accompanied by a psychiatric diagnosis.

Between 1996 and 2007, the proportion of doctor visits at which antidepressants were prescribed but no psychiatric diagnoses were noted increased from 59.5% to 72.7%.

Researchers aren’t saying that this remarkable growth necessarily represents inappropriate use of antidepressants, and depression is underdiagnosed and undertreated in this country. But the rapid and marked increase of such prescribing habits have prompted researchers to call for scrutiny of the pattern to better understand the factors driving the trend and to develop “effective policy responses.”

Ramin Mojtabai, one of the study’s authors and a professor in the department of mental health at Johns Hopkins in Baltimore, said to WebMD, “What we are observing is that Americans are increasingly viewing psychiatric medications as a solution for a wide range of social and interpersonal problems and for dealing with daily stress [and] general medical providers appear to be going along with this trend. The irony is that many patients with major depression or anxiety disorders who could potentially benefit from treatment with antidepressant medications do not receive these treatments.”

Another source told WebMD that there may be another story line here. Doctors often get reimbursed at lower rates for treating psychiatric conditions, so they might be motivated to prescribe antidepressants but record them in patient charts as treatment for a nonpsychiatric problem. And there’s still a stigma attached to psychiatric illnesses, which could skew diagnoses.

The study authors suggest that if antidepressants are being prescribed for uses not supported by clinical evidence, there might be a need to improve providers’ prescribing practices, revamp drug formularies or vigorously pursue implementation of broad reforms of the health-care system. The point is to improve communication between primary care providers and mental health specialists.

The cost of treating multiple sclerosis (MS) with a certain class of drugs is significantly higher than the cost of addressing the symptoms of MS with other therapies, according to a study in the journal Neurology.

Analyzing data from 844 individuals with early-stage MS and projecting health-care costs, including the cost of the drugs and lost productivity over a 10-year period, the study found that MS patients using disease-modifying drugs experienced modest health gains. But the cost associated with using such drugs is more than eight times higher than what is considered “reasonable” from a cost-effectiveness perspective.

“While it is clear that disease-modifying drugs are beneficial to some MS patients, those gains come at a tremendous economic cost,” said Katia Noyes, Ph.D., M.P.H., associate professor in the Department of Community and Preventive Medicine at the University of Rochester Medical Center and lead author of the study. “These results point to the need to continually evaluate the cost-effectiveness of new treatments in the interest of controlling health care costs.”

MS, a disease of the central nervous system, is the most common cause of neurological disability in young adults, causing muscle weakness, numbness or tingling in arms and legs, difficulty with coordination, balance and walking, blurred vision and slurred speech. The disease first manifests in cycles of acute symptoms followed by periods of remission and recovery. Eventually, the symptoms generally become debilitating.

Several new drugs introduced in the 1990s modified the course of the disease; traditional therapies primarily treat the symptoms of the disease. The drugs have been shown in large clinical studies to slow the progression of the disease and reduce relapses, but are associated with side effects and are very expensive -- as much as $30,000 per year.

The researchers employed a method called quality-adjusted life years (QALY) to evaluate the health effects of the drugs. QALY is a standard tool for evaluating disease burden by estimating the improved quality of life gained over time from a particular medication or course of therapy. Health policy experts generally accept that for an intervention to be judged “cost-effective” it should cost $100,000 or less to produce an extra QALY. According to the study, disease-modifying drugs for MS cost more than $800,000 per QALY.

And that came with only a modest improvement in health, according to the study. For example, MS patients taking one of the drugs gained about two quality-adjusted months over 10 years compared with patients who did not take disease-modifying drugs. They had an average of six out of 10 free of relapses compared with five years for patients not taking the drugs. The authors also found that the benefit to patients was greater if they began taking the drugs early during the onset of the disease.

Blogger Jim Edwards has a list of "10 Weird Health Theories That Just Won't Go Away."

Many of them flower from the backlash to the medical industrial complex's desire to medicalize, and provide a pill for, all slightly different human behaviors. Others underscore how appropriate skepticism about modern medicine can lead to an over-correction and an endorsement of wrongheaded and dangerous ideas (autism being caused by vaccines as a prominent example).

Here's the list of myths:

• "The so-called obesity epidemic is just a scare tactic to make you feel bad"

• "Human growth hormone is the fountain of youth"

• "Women who don't like sex have female sexual dysfunction"

• "Low-dose naltrexone cures everything"

• "Multiple sclerosis is caused by blocked jugular veins"

• "Taking multivitamins can prevent prostate cancer"

• "High cholesterol is not a health risk" [Note from Malone: This one is complicated.]

• "The feds want to microchip you like a pet cat"

• "HIV is not the cause of AIDS"

• "Vaccines cause autism"

As of this autumn, Tylenol is losing part of its punch. Manufacturer Johnson & Johnson is reducing the maximum recommended dosage on products containing acetaminophen, the main ingredient in Tylenol. The risk of liver damage from too much acetaminophen has long been a problem.

Most cases of liver damage occur when consumers take more than the prescribed dose of acetaminophen within a 24-hour period, take more than one acetaminophen product or consume alcohol regularly before taking acetaminophen.

When reformulated, Extra Strength Tylenol's recommended maximum daily dosage will be 3,000 mg per day, down from 4,000 mg per day. Earlier this year, the FDA imposed new limits on acetaminophen in prescription painkillers including Vicodin and Percocet, which contain other pain-killing compounds. Over-the-counter meds with acetaminophen were not affected by the FDA's restriction.

According to AboutLawsuits.com, more than 400 people per year die, and 42,000 are hospitalized, from overdoses due to drugs that use acetaminophen.

Technology is a wonderful thing. Most of us rely on it to do our jobs, remain informed, communicate and plan and participate in recreational activities.

But like a wonder drug that can render a dread disease a manageable irritant, technology has side effects and some of them are dark, indeed. Writing on his health news blog, Gary Schwitzer recounts the ominous tale of a pharmaceutical company's sly efforts to pretend to be a Facebook friend but whose motives were clearly mercenary.

Marilyn Mann is a well-informed medical consumer; she has to be, she's a breast cancer survivor whose daughter has heterozygous familial hypercholesterolemia (FH), a genetic disease that elevates LDL cholesterol to dangerous levels. She is an administrator of a Facebook group--Familial Hypercholesterolemia (FH) Discussion Group--that enables networking for people with FH and their family members.

Schwitzer reports that recently, Mann got a message from a public relations woman who had joined the Facebook page: "A few months ago, I had emailed you about some research I was doing about a new treatment for FH. I am now working with a pharmaceutical company, and the company currently has a drug in development to help treat people with severe FH that may not be responding to current therapies."

The PR woman continued: "I am trying to do exactly what you are doing--to educate patients and physicians about this disease and to raise awareness so that undiagnosed patients can get the help they need. ... I thought it might be good for us to connect so that I can explain to you a little about what the company is doing and to see how we can work together to reach a larger audience. Through my work in FH, I am regularly in touch with many of the world's leading researchers and the people who work at the company to discuss ways we might be able to collaborate...."

On its face, the approach was friendly and compassionate. Mann spoke with the PR woman, who disclosed that she was working for Genzyme, the company developing the drug to treat FH. The woman wanted Mann to recruit journalists to generate stories about people with FH.

Mann politely declined, saying, "Genzyme's purpose is to sell their products. My purpose is to help patients. Those two goals are not the same."

Not only was the PR person actively trying to manipulate the news--there's a difference between raising awareness about a disorder most people never heard of and working to ensure your employer has skin in the game--but her behavior could be seen as a form of electronic stalking. "I think it was creepy for this PR woman to join the Facebook page,"Mann told Schwitzer, "lurking there and observing on behalf of her drug company client. The idea of having a drug company planting human interest stories in the press is yucky ...a big corporation pulling string behind the scenes. I'm not interested in being used in that way."

As the informed person she is, Mann knew about the Genzyme drug, believed it had limitations based on trials and so informed the PR person.

The PR rep had clearly identified herself, her employer and the nature of her interest in the Facebook community. So why was her attempt to exploit it so unseemly?

As Schwitzer noted, it wasn't just the attempt to join a discussion group because of its potential usefulness for a certain company, it was the attempt to influence news coverage that that was so offensive. Whether you're voting for your local school board, signing a legal contract or making a determination about treatment for a medical condition, you need objective, complete information. Such decisions aren't made by listening to feel-good human interest stories.

Genzyme intended its FH drug not as first-line therapy, but as an additional treatment for people whose cholesterol is not controlled with a statin. Typically, those patients have the most severe forms of FH. It is their stories Genzyme wants the media to tell, not those of people who can control their cholesterol with a statin--they don't need another drug.

Schwitzer says tactics like those of Genzyme might fall under the category of "disease mongering," an effort to "sell" sickness by profit-driven interests beyond the boundaries of what science and medicine accept. The subject is well covered in PloS Medicine by writers Ray Moynihan and David Henry. The point, they say, is to sell products, not to inform, educate or otherwise help medical consumers understand and maintain their health.

If you're a member of a medical-topic social media group, be aware that sometimes a fox gains entry to the henhouse with very little commotion. If you're asked to tell your story, or to find other people who will, make sure it's for the greater good, and not just somebody's bottom line.

Aching back, stiff fingers, cranky knees... We like to self-prescribe common painkillers such as ibuprofen (Advil), naproxen (Aleve) and celecoxib (Celebrex) for all manner of discomfort. But a new study from the University of Florida casts renewed doubt on the long-term use of these drugs known as NSAIDS--nonsteroidal anti-inflammatory drugs.

It found that people with hypertension and coronary artery disease who address chronic pain with regular NSAID use may have increased risk of death from heart attack, stroke and related events.

Physicians already discourage the use of NSAIDs by heart attack patients and the elderly because earlier studies showed a relationship between the drugs and higher risk of stroke and heart attack.

People who also take aspirin--another type of NSAID--for cardiovascular prevention might be especially at risk because these other NSAIDS appear to compromise aspirin's anti-clotting effect, might increase the risk of bleeding and raise blood pressure.

The study's authors advise patients not to stop prescribed use of these drugs before discussing it with their doctors. Further studies probably will focus on whether all NSAIDS share these dangerous properties, or only some.

The road from conception to useful application for a new drug therapy, when properly navigated, is fully mapped, carefully followed, scientfically rigorous and honestly appraised. Not so with a big study of the lucrative drug Neurontin, according to Yale researchers.

In the case of Neurontin, a drug to treat epilepsy, critical parts of that journey took a few unauthorized detours, according to a report in the Archives of Internal Medicine.

Researchers at the Yale School of Medicine reviewed documents relating to the epilepsy drug gabapentin, a drug patented as Neurontin by Pfizer in 1994, that they concluded were misrepresented by the pharmaceutical company as a clinical trial.

Instead, they said, it was a “seeding trial,” which they described as “An important and expensive form of marketing, … a study of an approved drug or device in which the primary objective may not be to answer an important scientific question but rather to introduce a new product and induce clinicians to use it.”

In other words, seeding trials juice the market by enticing practitioners to sample and prescribe a drug that’s already FDA-approved.

Joseph Ross, M.D., said that Study of Neurotonin: Tritrate to Effect, Profile of Safety (STEPS) “was a seeding trial posing as a legitimate scientific study. The trial itself, not trial results, was part of a marketing strategy used to promote gabapentin and increase prescribing among investigators without informing trial patients or investigators."

As noted in the Los Angeles Times, the STEPS study also was intended to fend off efforts by a competitor to introduce a rival drug.

The breach wasn’t against the law, but it wasn’t ethical because the purpose was primarily to promote, not to discover, and because trial participants and physicians might be unaware of the studies’ true purpose.

The Yale team said STEPS’ stated purpose was to examine doses of gabapentin within a patient population of 2,759. Two articles about its results were published in scientific journals, but, the team noted, outside sources had questioned the study’s design as uncontrolled (that is, it didn’t include a separate, or "control," group of participants who didn’t receive the drug). In addition, it was not a blind study. Scientific rigor demands that study participants remain unaware—blind—about whether they are receiving a drug or a placebo (fake drug).

There's more. The Yale team said, "Data quality during the study was often compromised," and some documents appeared to suggest that marketing personnel helped to collect data and witnessed the trial, not just the results.

Article first published as Neurontin Research Was So Flawed It Deserved to Be Called Marketing, Not Science on Technorati.

You fill a prescription with a brand-name medication. The pills are light-blue ovals that come in a plastic bottle. When the generic version becomes available, your insurance company insists that you purchase only that, and your doctor agrees.

This time, the pills are round, white and come in a carboard blister pack. If the medicine works the same, who cares?

Two physicians writing in the New England Journal of Medicine, argue that we all should.

They say letting generics look like the brand name original makes for safer and even more effective medicine.

The doctors argue against a practice called "trade dress." The term refers to federal laws that protect the unique appearance of brand-name drugs by prohibiting generic pharmaceutical manufacturers from making similar-looking pills or designing similar packaging.

The researchers accept that trade dress has played a meaningful role in keeping drugs safe. It can prevent different medications from being mistaken for each other, thwart counterfeiting and prevent shady pharmacists from making unauthorized substitutions of generic for brand-name drugs and skimming the extra profit for themselves.

But drugs that are supposed to perform one way but look different every time you refill the prescription, suggest researchers Jeremy Greene and Aaron Kesselheim, can lead to medication errors, can be unnecessarily more expensive and can diminish the generic drugs' effectiveness, thanks to the placebo effect not kicking in for the generic drug.

A placebo, or "fake" drug, is a sugar pill or other inert substance used in medical trials to test different treatments among trial subjects who are unaware if they are being given medicine or something that just looks like it. Often, however, patients receiving the placebo respond positively, sometimes strongly so.

As reported on MedPage Today, The NEJM researchers note that "A resurgence of research on the placebo effect suggests that drug appearance can have a distinct functionality." They say a medication's packaging and the perceived dollar value of products can influence a product's effectiveness as well.

So because one medicine that always looks different can be confusing, because generics make up about 70% of all U.S. prescriptions but less than 20% of prescription-drug costs and because a patient's mind is a powerful player in his or her ability to heal an ailing body, the researchers support amending regulations to permit generic drugs to resemble their brand-name counterparts.

Such changes would codify a consistent, organized system of pill appearance that would:

• simplify the complexity of certain medical regimens;


• encourage the use of generic drugs when appropriate; and


• increase a patient's ability to take the medication as directed.

A drug prescribed for smoking cessation is linked to an increased risk of heart problems, according to a study published July 4 in CMAJ (Canadian Medical Association Journal). Varenicline, known by the brand name Chantix, was associated with a 72% increased risk of a serious cardiovascular "event."

That sounds huge, but the scientific number-crunching shakes out a bit differently. Although attention must be paid, many critical minds are not ready to dump the drug. Fifty-two (1.06%) of the participants who took Chantix had serious cardiovascular events compared with 27 (0.82%) of those who took a placebo.

One bottom line for smokers who may want to rationalize continuing to puff: It's always better to stop smoking. No excuses.

When varenicline was launched in 2006, the FDA noted that it could raise the risk of cardiac problems, and the federal agency recently updated the label for Chantix to reflect that risk among smokers with heart disease. And we wrote about the drug a couple of years ago. But the new study's authors said, "These increased risks ... are seen in smokers with or without heart disease."

The irony, of course, is that one major risk of smoking is heart disease.

The Chantix-using subjects of this trial were able to abstain from smoking at a significantly higher rate, an achievement that should potentially confer a cardiovascular benefit. Many members of the medical community believe the drug should remained a valuable treatment option, given the devastating effects of smoking. Apart from heart issues, nicotine and the other ingredients of cigarette smoke, of course, compromise lung function and can lead to lung cancer, and also increase the risk of stroke and diabetes.

The results were based on a review of 14 studies of approximately 8,200 smokers or users of smokeless tobacco. Most had no history of heart disease. They were followed for as long as a year, a comparatively short term that gives many researchers pause. It's possible, for example, that the risk diminishes over time.

Dr. Taylor Hays from the Mayo Clinic opined, "Although these results suggest a measure of caution should be taken in prescribing varenicline for tobacco dependence treatment ... [T]he risk for cardiovascular events is low and is far outweighed by the benefits of diminishing the truly 'heartbreaking' effects of cigarette smoking."

If you're taking Chantix, don't stop without consulting your doctor. If you're unable to stop smoking via other methods, discuss the cost-benefit question of treatment with Chantix.

A couple of months ago we gave a shout-out to a physician who had written a commentary about Genentech's efforts to have the FDA bless the use of its drug Avastin for treatment of certain breast cancers. He had objected to the use of patient testimonials as compelling evidence to support such appeals because they're not science, they're marketing.

In what the company and its supporters probably consider honorable tenacity but thinking minds ascribe to naked greed and abuse of taxpayer resources, the FDA again this week is hearing the case for approving Avastin as a conditional treatment for certain breast cancers, never mind that studies have shown it to be neither life-prolonging nor markedly life-enhancing. In the face of life-threatening side effects, Genentech still champions the drug because it has helped some patients. Yes, Virginia, and some people make a living swallowing swords and eating fire, but such activity isn't, as they say in FDA-land, "generally recognized as safe."

Two editorials appearing this week in the New England Journal of Medicine speak in favor of science and respect for human life.

Genentech presented four arguments against the FDA’s proposed withdrawal of Avastin for breast cancer: one, the move has no precedent; two, the possibility of some patients benefiting justifies continued approval; three, individual patient choice should prevail; and four, ruling against Avastin will make future drug development confusing and discourage innovation. And, like the kid who throws the ball over the fence because he doesn't like the ump's call, Genentech also took a shot at the FDA committee considering the matter, calling it biased and requesting different judges.

We won’t dignify Genentech’s hissy fit, but, in order, here's why Genentech's appeal is folly.

One: Precedent for removing a drug’s indication for a specific disease is part and parcel of U.S. drug regulatory process.

Two: Just because some patients might benefit doesn’t mean there is enough benefit to outweigh the harm to many other patients taking this highly toxic drug. Such lazy extrapolation ignores the absence of Avastin data identifying the patient characteristics that are associated with the benefit. That's incomplete science, and it’s dangerous.

Three: Genentech’s position that “conflicting interpretations of data should be resolved in favor of retaining access and choice” is a direct contradiction of the FDA's mandate. As the NEJM commentary stated, "In a democratic republic, access and choice represent two among many values. The FDA must also protect scientific rigor, the integrity and legitimacy of federal regulations and guidance, and the public’s health. The agency’s reputation for using science to guide regulatory decisions in the public interest is its most critical institutional asset."

Four: FDA action to restrict a drug's use from some applications is common and practically perfunctory. Instead of chilling R&D, such a situation might effect more aggressive drug development--if Avastin offers little promise for patients with metastatic breast cancer, won't pharmaceutical companies be inspired to develop a better product? After all, that’s where the money is, and we all know what motivates Big Pharma.

On one side you have what Justice Hugo Black evocatively called "organized money" -- the corporate interests dressed, in this case, in the garb of drug manufacturers: White coats with hundred dollar bills stuffed in the pockets.

On the other side: Regular folks: consumers, patients, and individual doctors.

Who wins in the U.S. Supreme Court? This week, organized money won: twice.

By 5-4 votes in both cases, the Supreme Court decided:

* Generic drug manufacturers are immune from lawsuits for defective and misleading labeling on their products even if patients are injured.

* Drug manufacturers have a constitutional right to collect data on individual doctors' prescription-writing habits, to help them market to those doctors more effectively.

The second decision will help "Big Pharma," brand name manufacturers who work hard to goose sales of their drugs while still under patent, before the generics bring in cut-rate look-alike products. So in a way, the court was balanced: One bone thrown to the brand name drug makers, and the other to the generics. But consumers were on the short end of both cases.

Why is the drug marketing case bad for consumers and for patient safety? Because the state of Vermont, whose law was overturned by the Supreme Court ruling on "free speech", was trying to give some breathing space for doctors to make decisions about what drugs are safest and most effective for their individual patients, without having the manufacturers' sales people in essence spying on the doctors by tallying up their weekly patterns of drugs prescribed. Read more on this drug marketing case from Merrill Goozner's blog.

The other decision is even more obviously bad for consumers. This ruling, based on a bizarre interpretation of the federal law that lets generics copy brand name drugs once the patent has expired, gives generics absolute immunity from lawsuits by injured consumers -- so the generic companies will have no incentive to follow the safety records of the drugs they profit from and put out corrected labels. Read more on this one from the American Association for Justice.

Doctors who aren't directly involved in patient safety issues often sail through their careers without much awareness of how commonly errors and malpractice infect hospitals, clinics and medical offices. Then they become patients, and suddenly their world is turned upside down.

Itzhak Brook, M.D., has been a doctor for more than 40 years. He is an infectious disease pediatrician at Georgetown University Hospital in Washington, D.C. Then he got throat cancer a few years ago.

His cancer was successfully removed, but then it came back. He had to have his voice box -- the larynx -- removed, and the throat was reconstructed.

It was then that the errors began to pile up, or, as he puts it, “mistakes occurred at all levels of my care.”

Dr. Brook recorded these incidents before, during and after his surgery:

* Surgeons had failed to timely diagnose the recurrence of his cancer. It was finally observed by an astute resident via a basic procedure that allowed visualization of the pyriform sinus, which was where his tumor was located. Had his experienced surgeons done the same basic procedure, his tumor most likely would have been observed and removed much earlier.

* Surgeons mistakenly removed scar tissue instead of the cancerous lesion. A week after the surgery, pathological studies revealed that the tumor was actually farther down in the pyriform sinus. This error could have been avoided if frozen sections of the lesion itself, not just its margins, had been analyzed in the operating room. As a result, he had to undergo additional surgery to remove the tumor, which was more difficult because of swelling and changes to the surgical site due to the original operation.

* While still in the ICU one day after surgery, he experienced an airway obstruction and couldn’t find his call button, which had fallen on the floor. Though he was only a few feet away from the nurses station, he was unable to get the attention of staff but was ignored. (He couldn’t call out because he no longer had a larynx).

* In what was probably the most serious error, he was fed soft food by mouth far too early, which, following laryngectomy with flap reconstruction, can lead to failure of integration by the flap. It took 16 hours before the feeding was stopped, and only after Dr. Brook brought this to the attention of a senior surgeon. The error occurred because the order to start feeding was in fact intended for another patient.

In addition, nurses and other staff:

Did not clean or wash their hands.

Did not use gloves.

Took oral temperature without placing the thermometer in a plastic sheath.

Used an inappropriately sized blood pressure cuff (which produced alarming readings).

Attempted to administer medications by mouth intended to be given by nasogastric tube.

Dissolved pills in hot water and fed them through the feeding tube (thus irritating the esophagus).

Delivered an incorrect dose of a medication.

Connected a suction machine directly to the port in the wall without a bottle of water.

Forgot to rinse the hydrogen peroxide used for cleaning the tracheal breathing tube (causing
severe irritation).

Did not write down verbal orders.

Fortunately, despite all these errors, Dr. Brook did not suffer any long-term consequences. Still, his experience made him realize that a hospital is the least safe place for patients, and that all hospitalized patients should have a dedicated patient advocate such as a family member or a friend at their bedside.

Dr. Brook writes extensively about his experiences as a throat cancer patient on his blog. He also lectures to medical groups to try to get doctors and nurses to understand the human costs of the epidemic of medical error.

You can also read Dr. Brook’s account of his hospital experiences in the Journal of Participatory Medicine.

Diabetes medication Avandia will be pulled from pharmacy shelves in November because it poses a major risk of heart attack, the Food and Drug Administration has announced.

Under a new program effective Nov. 18, 2011, only certified physicians will be allowed to prescribe the drug, and then only to patients who've been informed of the risks and who will fill their prescriptions by mail order through specific pharmacies.

The new FDA guidelines limit the drug to patients already successfully treated with it or to those for whom it's pretty much a last-ditch effort to control blood glucose medically. In addition, healthcare providers and patients have to enroll in the Avandia-Rosiglitazone Medicines Access Program to prescribe and receive rosiglitazone medicines.

The restrictions to access are so tough that virtually no one will be able to obtain the drug, says Dr. Steven Nissen, chief of cardiovascular medicine at the Cleveland Clinic, who has long advocated more restrictions on the use of rosiglitazone (Avandia's generic name).

Avandia is also sold as a component in the combination drugs Avandamet and Avandaryl. It was approved in 1999 to lower blood-sugar levels in patients with type 2 diabetes. In 2007, Nissen published an analysis showing that the drug increased heart attack risk by about 40% in people with type 2 diabetes, who are already much more prone to heart attacks than people without the disease.

Subsequent studies confirmed the greater heart attack risk. In June 2010, more than half of the members of an FDA advisory committee recommended pulling Avandia from the market or tightening restrictions on its use, and in September, the FDA decided to impose restrictions.

Source: TheHeart.org

You can read the FDA’s decision here.

Testimonials from satisfied customers sell products. Every marketer knows that. But testimonials from patients are the wrong way to decide if a drug deserves an endorsement worth billions in sales from the Food and Drug Administration.

Why? Because, as a Virginia cancer doctor explains in a new article, the testimonials from happy cancer patients mask the fact that many other patients were not helped, or worse, were killed by the drug.

The drug now being pushed to the FDA by the testimonial technique is called Avastin. It's been proven to help patients with some kinds of cancers: colon, brain, lung and kidney cancers which have spread beyond their first site of discovery. It doesn't cure the cancer, but it can strangle a tumor's blood supply and thus shrink a cancer.

Avastin was tried with advanced breast cancer, but rigorous studies found that it didn't help quality of life for patients with breast cancer, and it didn't extend their lives, even measured by months. Plus it comes with serious side effects, the most prominent being the potential to cause a hole to suddenly develop in the stomach or intestines, which can be fatal.

So the FDA said the manufacturer couldn't market it for breast cancer.

Now Genentech, the maker of Avastin, is taking another run at the FDA, using testimonials from patients and treating doctors to try to get the agency to change its mind.

Dr. Frederick C. Tucker Jr., an oncologist in Fredericksburg, Virginia, wrote an "op-ed" piece in the New York Times commenting on this stratagem by the drug company:

[A]necdote is not science. Such testimonials may represent the human voices behind the statistics, but the sad fact is that there are too many patients who have been treated with Avastin but are not here to tell their stories.

Avastin will not disappear because of the F.D.A. decision. It remains available for treating other cancers, and research to find its appropriate role in breast cancer treatment continues. In the meantime, the F.D.A., which is expected to make its decision in September, needs to resist Genentech’s attempt to have it ignore scientific evidence.

Serious progress in the treatment of cancer will not be the result of polemics, lobbying or marketing. Genentech’s money and efforts would be better spent on research for more meaningful treatments for breast cancer.

The Avastin website has photos of real patients who Genentech says have been helped by the drug. These photos tug at viewers powerfully. But they don't substitute for hard statistical analysis.

Physicians, researchers, drug makers and regulators should pay more attention to patients’ first-hand reports of their symptoms while they take medicines because their information could uncover safety problems and guide treatment and research, a cancer researcher says.

In an article in the New England Journal of Medicine, Dr. Ethan Basch, an oncologist who treats men with prostate cancer at Memorial Sloan-Kettering Cancer Center in New York, writes that direct reports from patients are rarely used during drug approval or in clinical trials, and, when patients’ comments are sought at all, they are usually filtered through doctors and nurses, who write their own impressions of what the patients are feeling.

In addition, physicians and nurses “systematically downgrade the severity of patients’ symptoms” and sometimes miss side effects altogether. One result is “preventable adverse events” — for instance, suicidal thoughts in young people taking antidepressants, or severe constipation in people taking a drug for irritable bowel syndrome, both of which might have been detected earlier if symptoms had been systematically tracked.

Basch first studied people who receive chemotherapy, comparing symptom reports by patients with those from doctors and nurses and found that for every problem — fatigue, nausea, appetite loss, vomiting, diarrhea, constipation — patients reported it earlier and more often than did doctors and nurses.

The tendency to downplay symptoms may be based on the doctor’s knowledge that a patient is in the early stages of an illness and could be much worse. Or the doctor may be making mental comparisons with other patients who are sicker.

Sometimes, the downgrading may reflect wishful thinking by doctors, who may think that a certain drug will help patients and don’t want to take them off it.

Mistakes and distortions in reporting symptoms can be compounded in studies, where one researcher collects the information, another retrieves it from the chart and enters it into the study record, and still others evaluate it. The results can be like playing broken telephone.

He recommends that patient symptoms should be rated separately by patients and their physicians, particularly before and after new medications are approved and brought to market.

Source: The New York Times

You can read the original article in the New England Journal of Medicine here.

Several Supreme Court justices strongly suggested recently during oral arguments that Vermont’s attempt to restrict the use of drug prescription records for marketing purposes violates corporate free-speech rights. Vermont’s law is aimed at so-called data miners, companies that buy prescription records from pharmacies — minus patient identifying information — and sell them to drug makers.

The drug companies use the information to target doctors to try to persuade them to order the companies' products. Vermont Assistant Attorney General Bridget C. Asay told the court that the state’s interest is to “allow doctors to decide whether this information that they’re compelled to provide to pharmacies may be used in marketing that is directed at them.”

But skeptical justices hurled a barrage of questions in return, asking whether the state’s goal was simply to make it harder for drug manufacturers to convince doctors that their drugs should be prescribed instead of cheaper generic drugs.

“The state is interested in promoting the sale of generic drugs and correspondingly to reduce the sale of brand-name drugs,” Justice Ruth Bader Ginsburg said. “And if that’s the purpose, why doesn’t that run up against what this court has said — that you can’t lower the decibel level of one speaker so that another speaker, in this case the generics, can be heard better?”

Asay insisted that drug manufacturers are still free to pitch any message they want, but that doctors don’t want their histories of prescriptions to be used to target them. The Vermont law lets individual doctors "opt out" of having their prescription histories sent to the drug manufacturers.

There’s no doubt that pharmaceutical companies have an easier time if they have such information, she said, but “they have no First Amendment right to demand it, just as they have no right to demand access to the doctor’s tax returns, his patient files, or to their competitors’ business records.”

The federal government and 35 states are siding with Vermont in the fight, which has split lower federal courts.

The case is Sorrell v. IMS.

Source: The New York Times

Medication errors in a hospital’s psychiatric unit were cut drastically with two techniques: an electronic prescription drug ordering system and a computerized method to report adverse events, according to new research from Johns Hopkins University.

The leader of the study, Geetha Jayaram, MD, MBA, an associate professor of psychiatry and behavioral sciences at Johns Hopkins School of Medicine, says that “with the use of electronic ordering, training of personnel and standardized information technology systems, it is possible to eliminate dangerous medication errors” altogether.

The findings published in the March issue of the Journal of Psychiatric Practice illustrate how the psychiatric unit at The Johns Hopkins Hospital in Baltimore went from a medication error rate of 27.89 per 1,000 patient days in 2003 to 3.43 per 1,000 patient days in 2007. And none of the medication errors during the study period caused death or serious, permanent harm, Javaram notes.

“Having something typed eliminates bad writing — and most errors — immediately,” she says. “It’s a good reason for going electronic.” Medication errors, which can be lethal, are known to be caused by illegible handwriting, misinterpretation of orders, fatigue on the part of medical personnel, pharmacy dispensing errors and administration mistakes. A pharmacy may misread what a physician has written or give the wrong medication or the wrong drug dose to a patient.

The computer program used in the psychiatric department also includes integrated decision support for drug dosage selection, drug allergy alerts, drug interactions, patient identifiers and monitoring — things that can be lost with a manual system that relies on layers of human beings to ensure the correct decisions are made, Jayaram says. The more the number of steps involved in the process, the greater the likelihood of mistakes.

Source: Scienceblog

You can read the complete study here.

Drug manufacturers claim their products are pricey because of the high cost and high risks involved in getting new drugs to market. But a recent study shows that these high cost estimates have been constructed by industry-supported economists and that R&D costs are not the barrier to drug development the drug companies maintain they are.

The study, by researchers at Stanford and the University of Medicine and Dentistry of New Jersey and published online in Biosocieties journal, also shows that current incentives reward companies for developing new medicines of little advantage that compete for market share at high prices, rather than clinically superior medicines with public funding that would reduce the price of drugs to consumers and actually lower risk to the pharmaceutical companies.

The study takes aim at drug companies’ inflated cost estimates and shows exactly where they are wrong. For example, figures typically bandied about -- $800 million or $1.3 billion to develop a new drug – do not include the 39% contribution made by taxpayers through tax write-offs for R&D. Furthermore, the study shows that the industry-based figures are based on clinical trials (and number of participants) that are much larger than actual trials reported by the FDA and the National Institutes of Health.

Even worse, as much as half of the industry estimates are not real costs, but exaggerated estimates of profits that companies might have made if they put their money in the stock market instead of developing the drug. And even if the notion that foregone profits should be included as a cost – which, according to the study authors, no other industry does – U.S. government guidelines call for using three percent, not the 11 percent used to arrive at the $800 million figure.

In essence, the study argues, pharmaceutical companies “have it both ways,” treating R&D costs as though they were long-term capital investments even though the the taxman treats them like ordinary, fully deductible business expenses.

The study concludes that the real cost per "self-originated" drug product is closer to $180-231 million, noting that “the mythic costs of R&D are but one part of a larger, dysfunctional system that gives us mostly new medicines that have few or no advantages and serious side adverse reactions that have become a leading cause of hospitalization and death.”

Source: Alison Bass blog

You can read the report here.

The news this week from the Centers for Disease Control and Prevention that as many as 48 million U.S. adults have high levels of bad cholesterol, and aren’t doing enough to control it, left out one conspicuous controversy: Should lots more Americans be taking statin drugs, or would it be a huge waste of money?

Statins like Crestor and Lipitor lower cholesterol in the blood by decreasing cholesterol synthesis in the liver. Since plaques in coronary arteries are mostly composed of cholesterol, lowering cholesterol cuts the rate of formation of plaque, and in some cases, even shrinks it.

For people with diagnosed heart disease, statins are mainstream, non-controversial medical treatment. But for patients who just have high cholesterol, but no known heart disease yet, the drugs have modest if any benefit. And this is the group that is the main target of drug manufacturers for expanding sales of statins.

A cautionary statement about the questionable role of statin drugs in "primary prevention" of heart disease was recently released by the British-based Cochrane Collaboration, which conducts rigorous reviews of medical studies to see how the evidence measures up.

The authors of the new Cochrane review criticized much of the studies sponsored by drug manufacturers for leaving out key data. They concluded:

Only limited evidence showed that primary prevention with statins may be cost effective and improve patient quality of life. Caution should be taken in prescribing statins for primary prevention among people at low cardiovascular risk.

Doctors who are slow to turn healthy people into medical patients are careful about whom they prescribe statins for. For example, Dr. Robert Lemmon, a South Carolina family practice doctor and medical blogger, wrote an analysis of the published studies and concluded that statins were "overrated" and did not much help people who don't have heart disease. Noting that other cautious reviewers had reached the same conclusion, even though it cuts against drug manufacturer hype, he wrote: "This post is blasphemy. Fortunately I am in good company."

The CDC report also talks about improving diet and exercise habits as strategies to cut cholesterol. That can work in individuals very well, but as a public health strategy, education campaigns also fall short in making any notable impact. That's why public health advocates reach for systemic changes that would expose people to less temptation by strategies such as bans on use of certain bad fats in restaurants and fast food manufacturers. A provocative article on this topic was published in PLoS Medicine.

Article first published as Government Reports Millions of Americans Have Untreated High Cholesterol — But What Treatment Works? on Technorati.

A panel of experts set up to probe the effectiveness of opioid treatment agreements has decided not to support the universal utilization of these arrangements, also known as pain agreements or pain contracts.

Pain agreements outline the risks and benefits of opioid therapy, explain what is expected of the patient, educate the patient about how to store the drugs and help the patient distinguish between acceptable and unacceptable drug-taking. Physicians who provide pain management to patients with chronic pain may require such agreements to avoid liability issues if patients misuse their medications.

However, critics say the agreements can result in a more adversarial physician-patient relationship (because the physician can “fire” the patient if he or she doesn’t adhere to the terms of the “contract”).

The real problem, many critics maintain, is the lack of pain specialists. As a result, primary care physicians, many of whom lack appropriate training in pain management, may take the path of least resistance and overprescribe pain medications at the request of patients.

The panel of physicians and pain-policy experts, which was convened by the Center for Practical Bioethics, a Kansas City, Mo.-based think-tank, concluded it could not support the universal utilization of pain contracts at this time due to “the lack of data about the benefit of pain agreements/contracts, concerns about increasing disparities and further stigmatization of pain patients, and other possible unintended consequences, coupled with the importance of preserving the integrity of medicine from inappropriate outside influence.”

Source: American Medical Association News

For more information and analysis of the panel’s conclusions, click here.

To avoid the risk of "severe liver injury," the Food and Drug Administration (FDA) wants manufacturers of prescription combination products containing acetaminophen to limit the amount of acetaminophen to no more than 325 milligrams (mg) in each tablet or capsule. Manufacturers also will have to update warning labels on these products to alert consumers about the potential risks.

Acetaminophen, better known as Tylenol, its most popular brand name, is a pain reliever and fever reducer sold over the counter (OTC) as well as in prescription products in combination with other ingredients, such as codeine (Tylenol & Codeine), oxycodone (Percocet) and hydrocodone (Vicodin). The FDA action affects prescription products only, not OTC medications.

“FDA is taking this action to make prescription combination pain medications containing acetaminophen safer for patients to use,” said Sandra Kweder, M.D., deputy director of the Office of New Drugs in FDA’s Center for Drug Evaluation and Research (CDER). “Overdose from prescription combination products containing acetaminophen account for nearly half of all cases of acetaminophen-related liver failure in the United States; many of which result in liver transplant or death.”

The elimination of higher-dose prescription combination acetaminophen products will be phased in over 3 years. “There is no immediate danger to patients who take these combination pain medications and they should continue to take them as directed by their health care provider,” Kweder said. "The risk of liver injury primarily occurs when patients take multiple products containing acetaminophen at one time and exceed the current maximum dose of 4,000 milligrams within a 24-hour period.”

Because of continued reports of liver injury, FDA also wants to see boxed warnings, the agency’s strongest warning for prescription drugs, added to all acetaminophen prescription products. Most of the cases of severe liver injury occurred in patients who took more than the prescribed dose of an acetaminophen-containing product in a 24-hour period, took more than one acetaminophen-containing product at the same time or drank alcohol while taking acetaminophen products.

Source: Food and Drug Administration.

Click here for more information and a list of affected products.

There is growing concern among pharmacists in developed countries, including the U.S., that drug counterfeiting is a serious problem that current policies and technology have been unable to solve.

In a recently published survey commissioned by Pfizer and the International Pharmaceutical Federation (FIP), 63% of 2,000 community, retail and hospital pharmacists in the U.S., Europe and Australia believe current policies and technologies are insufficient to deal with drug counterfeiting, while 61% of those surveyed also say the prevalence of counterfeit medication is a serious issue in their country.

Long a problem in Africa and Southeast Asia -- where the World Health Organization has estimated that anywhere between 25% and 50% of medicines may be counterfeit – the number of these fake medications in the U.S. market has increased dramatically in recent years. In 2009, the U.S. Customs and Border Protection Agency stated that the value of seizures of counterfeit pharmaceuticals had increased by 500 percent over the previous 3 years. By some estimates, annual earnings from fake and substandard medicines worldwide is more than $32 billion.

A counterfeit drug is a pharmaceutical product produced and sold with the intent to deceptively represent its origin, authenticity or effectiveness. Generic drug products or drug products whose only violation is that of patent laws are not counterfeit drug products. A counterfeit drug may contain inappropriate quantities of active ingredients, may be improperly processed within the body (e.g., absorption by the body), or may contain ingredients that are not on the label (which may or may not be harmful), and is often sold with inaccurate, incorrect, or fake packaging and labeling.

Source: HealthcarePackaging.com

You'll find information on how to access an indepth study of the global drug counterfeiting problem here.

Or ... let them run through your body first, and then into the toilet. Either way, taking mega-doses of vitamins and other supplements just doesn't do much for people, other than enriching the vitamin content of their toilet water.

Latest proof: High doses of Vitamin D and calcium do nothing for most people, because the body gets plenty out of a normal healthy diet and from normal sun exposure (for making Vitamin D).

Worse, although less conclusive: Vitamin D can actually be harmful in large doses.

Here's a discussion of the latest evidence.

And what just is a vitamin, anyway? Here's an excerpt from an article on the subject at the website of the American Council on Science and Health, a debunker of health myths of all sorts:

Vitamyths

By Josh Bloom, Ph.D.

If you ask 100 people what a vitamin is, at least 100 of them will get it wrong. They will have some vague ideas: everyone should take them, they are derived from natural sources and the more you take, the healthier you will be. All of this is wrong.

The definition is actually rather simple: vitamins are nutrients required in very small amounts to promote many of the thousands of chemical reactions that make life possible. Most vitamins function as catalysts — substances typically used in miniscule quantities to promote these reactions that would otherwise not take place or would do so millions of times more slowly. Vitamins must be consumed because (with few exceptions) they are not produced within the body.

The quantity of vitamins actually needed is unexpectedly small. If you add up the total weight of all vitamins in the Recommended Daily Allowance (RDA) you come up with 150 milligrams, roughly equivalent to 5 grains of uncooked rice. This tiny amount is sufficient to support a wide-ranging array of biochemical reactions that generate energy, synthesize proteins and regulate hormone levels, just to mention a few.

Surprisingly, nearly all vitamin supplements come from synthetic rather than natural sources. The two forms are chemically identical and your body cannot tell them apart, so the source is immaterial. Even vitamin C, which could easily be extracted from fruits or vegetables, is man-made in vitamin pills.

More surprisingly, large doses of vitamins can be harmful and even fatal. [Emphasis added by protectpatientblog.] Vitamins are divided into two classes: water-soluble and fat-soluble. Each group behaves differently when taken in large quantities. Water-soluble (B and C) vitamins are less toxic, since they are rapidly excreted in the urine, where they nourish the life forms in your sewer at the expense of your wallet. By contrast, fat-soluble vitamins (A, D, E, and K) are stored in body fat, and they are eliminated much more slowly, making them more dangerous. Indeed, numerous studies have shown that large doses of vitamin E are associated with cardiotoxicity and early death. Excess vitamin A causes liver toxicity, anemia and hair loss, and is especially dangerous for the fetuses of pregnant women. It is chemically related to the acne drug Retin A, which can cause serious birth defects.

Read more here:

Patient safety advocates and brand-name drug makers lined up against companies that make generic drugs over just how flexible the standards should be for the clinical testing of biosimilars.

These drugs, also known as biogenerics, follow-on biologics and subsequent entry biologics, are officially approved subsequent versions of biopharmaceutical products following patent and exclusivity expiration on the original product. Until now, only a handful of biosimilars have been approved in the U.S., but that is about to change.

At the hearing, patient safety advocates argued that the only way to be sure that a drug is safe is through extensive clinical trials, while generic biosimilar manufacturers and distributors maintained that dangerous and expensive clinical tests are not required because they will be based on drugs that are already proven safe.

But are they? Biosimilars exhibit high molecular complexity and may be sensitive to manufacturing process changes. In addition, the biosimilar manufacturer doesn’t have access to any of the information or substances (e.g. molecular clone or cell bank) that the originator used to create the drug. As a result, patient safety advocates worry that biosimilars might perform differently than the branded versions, and could have potentially serious health implications.

Amgen, a brand-name biopharmaceutical manufacturer, called for biosimilars to undergo rigorous testing and recommended that the FDA:

1. Use well-designed clinical trials to establish biosimilarity

2. Ensure the product manufacturer and lot number is known for all administered biologics

3. Set scientific and practical criteria for interchangeability.

Critics of a rigorous clinical testing standard say that in addition to the expense, there are ethical questions involved in repeating potentially dangerous trials in humans. To avoid repeating human trials, U.S. Senator Bernie Sanders has proposed require generics makers to pay a fee for access to clinical data used in the manufacture of the brand name biologic.

Source: Wall Street Journal blogs

You can get more information about the FDA hearing and view video of the proceedings here.

A lesson in the safety and efficacy of new drugs is very simple: small studies are bad, big studies are good. This lesson has been proven all over again with a big trial of a heart failure drug called Natrecor (generic name: nesiritide).

Small studies made the drug look worrisome for some bad side effects. Now a big study has found those worries misplaced -- but it also found the drug doesn't work all that well for its main purpose of preventing fluid accumulation in the lungs of heart failure patients -- symptoms that give them a terrible feeling of near drowning.

As quoted in the New York Times, a leader of the study of nesiritide, Dr. Robert M. Califf, a Duke cardiologist, said:

“Once again, small studies give us the wrong answers. There was no safety issue at all. To me, the really important message is that the drug got very widely used for reasons that are incorrect, and then it got bashed for reasons that are incorrect. Unless we do these kinds of large clinical trials we are engaged in a comedy of errors.”

And more from Dr. Califf, talking about both nesiritide and another heart drug -- Zetia -- now under a big study:

“F.D.A. by mandate could require studies, but that wouldn’t be necessary if clinical trialists and academic medical centers stuck to their guns and demanded the evidence before they used the drugs on a wide scale. Huge amounts are spent on marketing that could have been spent on a clinical trial."

Listen up, Big Pharma.

As many as 180 medications are in short supply so far this year, according to data from the the Drug Information Service (DIS) at University of Utah Health Care, which has tracked drug shortages for a decade. DIS calls the number of shortages this year “unprecedented.”

Across the United States, life-saving or medically necessary drugs are in short supply, endangering care and increasing the odds of medication mistakes for a broad swath of patients. Health officials say drug shortages pose a growing public health crisis, fueled in large part by financial motives of pharmaceutical companies concerned about falling profits due to competition from low-cost generic products.

According to figures compiled by DIS, there has been a significant increase in the number of drug shortages since 2005, when 74 drug shortages were recorded across the U.S. By 2009, the number had more than doubled to 166. And as of Sept. 10 this year, it had logged 150 new shortages – in addition to 30 drug shortages still unresolved and more being reported every week.

This year, shortages have been reported for commonly used drugs such as morphine for pain relief, propofol for sedation and Bactrim injections for infections. The problem has reached such a peak that four leading groups representing cancer doctors, anesthesiologists, pharmacists and safety advocates have convened an invitation-only meeting in Bethesda, Md., on Nov. 5 and have asked pharmaceutical companies and supply-chain representatives to join them in efforts to solve the shortage problems.

According to Valerie Jensen, associate director of the Food and Drug Administration’s drug shortage program, about 40% of the shortages are caused by manufacturing problems, including safety issues, 20% are caused by firms ceasing production of a drug and another 20% are due to production delays. Shortages also may arise due to raw material shortages, increased demand, site issues and problems with parts such as syringes or vials.

The FDA can’t force drug manufacturers to address the problem because it lacks authority to compel them to continue producing a certain drug, or to require them to make a drug that’s in short supply. Nor are companies required to inform the FDA about impending shortages unless there is no alternative for the drug in question, and even then, there are no sanctions for not informing the FDA.

Source: MSNBC

For FDA information about drug shortages, go here.

Cortisone shots seem almost miraculous in their pain-banishing properties for sore tendons and joints. But a major new review article says they actually make tennis elbow worse and have long-term consequences when used for other tendon injuries too like Achilles tendon and sore shoulders.

For tendonitis, especially, cortisone seems to change the short-term biology of pain, but doesn't heal the underlying structural damage, which is usually due to overuse and not inflammation.

Patients who take cortisone tend to have higher rates of relapse and also are less likely to return to their baseline than patients who do nothing or take physical therapy, according to the review article in the Lancet, a prominent British medical journal. The findings were reported in the New York Times.

Read more here.

Infectious disease specialists are raising the alarm over a variant of the e.coli bacteria that is resistant to most of the antibiotics used to treat bladder infections and could be responsible for more than 3,000 deaths a year.

E.coli ST131, an aggressive strain of multi-drug-resistant e.coli bacteria, may be responsible for as many as 1 million bladder infections a year, according to a recent study conducted by Dr. James Johnson, an infectious disease expert at the Veterans Affairs Medical Center in Minneapolis.

E.coli ST131 is one resistance gene away from being untreatable, Johnson warns. “I think it’s high time to worry. Before, resistant strains were wimpy. Now, we have a winner,” he says.

Although e.coli is best known as the intestinal bacteria that causes diarrhea when people eat tainted meat or vegetables, such as spinach, it actually occurs more often outside the intestines, causing far more infection and death. Extra-intestinal e.coli is responsible for about 80 percent to 90 percent of the urinary tract infections that occur annually.

Most e.coli variants respond to common treatments: guzzling gallons of water, swilling quarts of cranberry juice, and, if all else fails, heading to the doctor for a quick course of antibiotics. However, Dr. Johnson’s study determined that although the e.coli ST131 strain accounted for only about 17 percent of e.coli isolates overall, it accounted for more than 50 percent of bacteria resistant to more than one antibiotic, including the top two types used to treat most urinary tract infections, or UTIs, and also was responsible for nearly 70 percent of resistance to the biggest guns of mainline UTI treatment, fluoroquinolones and extended-spectrum cephalosporins.

E.coli ST131 probably caused the most significant multi-drug resistant e.coli infections in the U.S. in 2007, the year Johnson studied, constituting a serious public health threat.

Dr. Johnson’s findings add to the growing concerns about drug-resistance in common infections such as UTIs. New UTI guidelines that will restrict the use of fluoroquinolones for large infections are expected to be issued by the Infectious Diseases Society of America this fall.

Source: MSNBC
You can read an abstract of Dr. Johnson’s study here.

Today's news has two reminders of why statisticians are our friends and allies when it comes to getting the right health care and avoiding dangerous and over-hyped treatments.

The headlines:

* Hormone replacement therapy after menopause not only increases the risk of getting breast cancer, but also makes the cancer more deadly. Details here.

* Taking a daily fish oil supplement in pregnancy doesn't make babies any smarter. Details here.

The arc of both stories is similar, and that's no coincidence.

Act One: Medical scientists develop a new treatment that, based on then current knowledge, should work.

In hormone therapy, the idea was that estrogen protected women from heart and blood vessel disease. This was based on a statistical notion -- since proven false -- that there was a big jump in heart attacks and similar disease after menopause, which must mean (so it was thought) that the drying up of estrogen in the body with menopause was depriving the body of a natural protectant.

In fish oil, the idea came from observations that DHA, a key fish oil ingredient, is naturally transmitted to a fetus in the last half of pregnancy and is important to brain development. And premature babies, born with low supplies of DHA, did better in some studies if they received DHA supplements in the first few months of life.

Act Two: Hopeful "observational" studies are published. These involve dozens to hundreds of patients and have very favorable results for the treatment in question.

Act Three: Manufacturers make big bucks pumping the treatment in question.

Act Four: Medical scientists do the hard work of large-scale studies where patients are "randomized" to the real treatment versus a dummy (placebo) treatment.

This takes years of carefully following patients and comparing outcomes.

Act Five: Enter the statisticians.

They come in, crunch the numbers and discover: It doesn't work (see today's fish oil study) or worse, it causes a lot of harm too (today's hormone story).

What's the lesson for the rest of us? As I wrote a few days ago on this blog, it pays to be skeptical of medical research findings, particularly when hyped by commercial interests.

Most people hear about research in the Act One, Two or Three stages.

If you wait till the story plays out in Acts Four and Five, you'll be less disillusioned, and safer and wiser too.

A diet drug which safety advocates called to be withdrawn from public use eight years ago has finally bit the dust. Under pressure from the Food and Drug Administration, the drug’s manufacturer, Abbott Laboratories, voluntarily pulled the drug from the market due to longstanding concerns that it increased the risk of heart attacks and strokes.

“There was no identifiable population of patients for whom the benefits of Meridia outweighed its risks,” said John Jenkins, MD, director of the office of new drugs at the FDA. “Meridia’s continued availability is not justified when you compare the very modest weight loss that people achieve on this drug to their risk of heart attack or stroke.”

The move was described as “commendable but dangerously too late,” by Sidney Wolfe, MD, a member of the FDA’s Drug Safety and Risk Management Committee and director of the Health Research Group of Public Citizen, a consumer and health advocacy group.

The pressure from the FDA came after results of a clinical trial involving more than 10,000 patients showed that people who took Meridia had a 16% increase in relative risk of heart attacks. The trial also showed that individuals taking Meridia only lost approximately 2.5% more weight than those on placebo and that the weight loss didn't last very long.

Abbott maintained these results weren’t relevant because most of the individuals in the trial had cardiovascular disease and should not have taken the drug in the first place. The company continues to maintaion that for the right patients, the drug is safe.

European regulators took the drug off the market in January 2010. An FDA advisory committee was split on whether to remove the drug, but the ultimately decided to recommend doing so because “there was no identifiable population of patients for whom the benefits of Meridia outweighed its risks,” Jenkins said, adding that he did not believe Meridia users would have any residual increased risk once they stopped taking the drug.

Source: The New York Times

You can view an abstract of the clinical trial that led to the FDA recommendation here.

Antipsychotic drugs have now become the top-selling class of prescription drugs in the United States, with $14.6 billion in annual revenue. Quite a trick for a group of drugs approved for one percent or less of the population.

But now you can go into any nursing home or elementary school and find non-psychotic patients taking these anti-psychotic drugs every day. Therein lies a marketing story for pharmaceutical manufacturers, who have danced around FDA regulations intended to keep the drugs marketed for only proven and safe uses.

The names include Abilify, Geodon, Seroquel, Zyprexa -- and the side effects include weight gain, drowsiness, nausea, involuntary body movements, and even diabetes.

The New York Times' Duff Wilson has a long takeout on this marketing story and the many lawsuits that have turned up industry documents showing how regulations are ignored and skirted.

Two quotes from this must-read story hit my eye:

“If you have a lot of money on the table and you have clinical uncertainty over mental health conditions, where you don’t have a blood test or objective test for it, you see it’s kind of a combustible mixture,” says Dr. Mark Olfson, a Columbia University psychiatry professor and researcher.

And this one:

“It’s the money,” says Dr. Jerome L. Avorn, a Harvard medical professor and researcher. “When you’re selling $1 billion a year or more of a drug, it’s very tempting for a company to just ignore the traffic ticket and keep speeding.”

Time was when the Food and Drug Administration would give a new drug the go-ahead for marketing based on a handful of studies involving no more than a few thousand patients. Then millions of prescriptions would be written over the next few years, and the drug would finally have its real test of safety on the open market, with the American consumer as the guinea pig. If the drug flunked the real-world test, it would be taken off the market, with a flurry of product liability lawsuits and calls for regulatory reform. This script is familiar from fen-Phen to Vioxx.

Now with the FDA's decision to split the baby in half with the diabetes drug Avandia, many are saying a new and different era of prescription drug safety is upon us. Instead of the old Up-Or-Down, and sometimes later Out, the FDA is setting up what one drug industry commentator, Gooznews, calls Permission Slip Medicine.

To get a prescription filled for Avandia -- and presumably other controversial drugs down the road -- a patient will have to hand the pharmacist a signed slip of paper acknowledging that he or she has discussed the medication with the doctor and both have decided together that they really, really want to have this drug, despite the availability of other alternatives like Actos which doesn't seem to carry the risk of heart attack and stroke that Avandia apparently has.

I say "apparently has" for Avandia, because the drug agency says it's not really sure. Part of its decision to punt on Avandia, keeping it available but harder to get, included posting on the FDA website a series of memos from top level agency staffers showing how very sophisticated drug reviewers could read the same studies and come to opposite conclusions on safety and the need for more research. Click here to see the memos. Note the contrast between the memo by FDA firebrand David Graham, who wanted Avandia yanked completely from pharmacy shelves, as has happened in Europe, and more conciliatory memos by long-time agency officials like Robert Temple.

In the old days, the other option for an in-between drug like Avandia would have been to add a dire statement to the official product labeling about the newly discovered risk. This has already happened for Avandia. These warnings are often called black box warnings because they appear in bold face at the very beginning of the columns of dense prose of the official language published in the Physicians Desk Reference and various online sources.

But who reads the black box warnings? Certainly lawyers like me do, when a client comes calling with a serious injury or death and it turns out the drug culprit didn't have such a black box warning, or their doctor didn't mention it to them. But if my experience is any measure, many doctors pay little attention to the official label. That's part of the long-running scandal of prescription drug education in the United States, which is dominated by the legions of drug salespersons who regularly trundle their briefcases of free samples and glossy handouts down the back hallways of doctor offices.

The new FDA action is intended to force doctor and patient to sit down quietly together and make a reasoned decision about whether this drug is right for this patient, despite the bad stuff that has happened to other people. That may be a good thing.

Avandia is one of the growing class of drugs that once you're on it, you swallow the pill every day for the rest of your life. The goal for Avandia is to lower blood sugar in diabetics, and that can prevent other bad long-term issues like diabetic blindness (retinopathy) and kidney disease. So the good intent is there.

But with a safer alternative apparently out there, what's the point of loading extra risk onto the patient? That's a dialogue that the FDA has now shifted from its officials onto the desks of individual doctors.

Until now, it’s been easier to rate appliances and restaurants than surgeons in most parts of the country, but that should change now that surgeons who perform cardiac bypass surgery are being rated on objective quality measures in Consumer Reports magazine.

The consumer magazine recently published ratings of 221 surgical groups in 42 states online. The same ratings will be available in the October print issue. To date, only a few states, such as New York, compile data-based ratings of physicians.

The data Consumer Reports used to rate the physicians was collected the Society of Thoracic Surgeons, which includes more than 90% of cardiothoracic surgeons in the U.S. in its membership. Physician groups, not individual surgeons, were rated either above average, average or below average based on (a) complication and survival rates; (b) the surgical technique used; and (c) the type of medication(s) the patient was sent home with after surgery.

An article in the New England Journal of Medicine called the move to make this data public “a watershed event in health care accountability.”

The 221 groups rated in Consumer Report represent less than a quarter of physician groups that perform bypass surgery in the U.S., as only surgical groups that allowed their information to be published were rated. Of these, only five were rated below average, which is fortunate, because the gap in treatment between a below-average and an above-average surgical group can be extremely wide; for instance, at an above-average hospital, patients had a 92% chance of receiving the recommended medications when leaving the hospital; at one of the below-average hospitals, patients had only a 24% chance of getting the recommended drug.

For now, the information is available only to people who subscribe to Consumer Reports online and print subscribers. However, STS says it will make the ratings freely available on its web site in a few months.

Source: New York Times
Visit the web site of the Society of Thoracic Surgeons (STS) here.

A new patient safety organization has launched a range of online tools and other resources to reduce abuse of opioids by identifying the risks associated with their use. The materials from the CARES Alliance (Collaborating & Acting Responsibly to Ensure Safety) include several “safe-use” programs, tools and educational materials for patients, caregivers and healthcare providers.

They were developed using Failure Mode and Effect Analysis (FMEA), a scientific methodology that identifies where problems occur in the use of pain medications and the underlying causes of those problems. The FMEA research identified 79 areas where problems occur in the use of opioidsand 290 potential causes of those failures.

Tools now available include clinical materials and risk assessments for physicians, safe-use guides for patients and general education for all groups. The organization also plans to develop additional tools based on the research.

Jeffrey Gudin, MD, a pain management and addition specialist at the Englewood Hospital and Medical Center in Englewood, N.J., says that healthcare professionals need to do a better job of assessing our patients' pain medication needs and of communicating the risks of the medications they prescribe.

"Through the resources of the C.A.R.E.S. Alliance, patients, caregivers and health professionals will have access to information, tools and resources to help them better understand these risks and better ensure that the medications are used properly by only those for whom they are prescribed," he says.

The alliance, which is sponsored by Covidien, the largest producer of prescription pain medications in the U.S., also will work to ensure that patients suffering from chronic pain have access to necessary medications.

Source: Medical News Today
You can obtain tools and other resources here.

Healthcare providers need to know more about the efficacy and potency of hydromorphone, a pain killer frequently used as a morphine substitute in post-operative patients, to avoid medication errors and adverse drug reactions (ADR), says an advisory from the Pennsylvania Patient Safety Authority (PPSA).

Researchers hired by PPSA reviewed 1,694 medication error and 937 adverse event reports involving hydromorphone from January 2008 to October 2009. They identified lack of knowledge about hydromorphone potency and the difference in potency between morphine and hydromorphone as the most significant factors causing serious medication errors, particularly when a patient is switched from morphine to hydromorphone.

Hydromorphone is administered in doses that range from 0.4 mg to 2 mg, whereas patients may receive as much as 7-10 mg of morphine. Incorrect dosing may occur when prescribing, dispensing or administering hydromorphone when a physician, pharmacist or nurse confuses hydromorphone and morphine. Other medical errors noted in the study were giving patients the wrong drug and not noting a documented allergy.

Some adverse drug reactions to hydromorphone also may be preventable. The study found that of the 447 reported ADRs involving central nervous system or respiratory effects, 292 (65%) were preventable, and, of these, 205 (70%) resulted from dosing errors.

To reduce the number of medical errors and ADRs involving hydromorphone, the study recommended implementing risk reduction strategies such as constraints and standardization, which focus on system improvement. It also recommended writing hydromorphone with the first five letters capitalized (i.e. HYDROmorphone) to further distinguish it from morphine.

Source: Pennsylvania Patient Safety Authority
You can view the report here.

A study published in the Journal of the American Medical Association concludes that low-dose corticosteroid medications administered orally – which result in significantly fewer adverse effects – are just as effective as high-dose intravenous steroid injections in treating patients with chronic obstructive pulmonary disorder (COPD).

Corticosteroids figure largely in the treatment of COPD, either on their own or in conjunction with bronchodilators. However, their optimal dose and route of administration are uncertain. Currently, there are two basic options for the administration of corticosteroids in hospitals: (1) to administer the drugs orally at a lower dose (i.e. 60 mg over 2 days); or (2) inject a higher dose (i.e. 600 mg over 2 days) intravenously.

Although the recommended treatment is to administer the lower dose orally, nearly all (92%) COPD patients receive the higher-dose intravenous injections, increasing their risk of having an adverse event.

The study was conducted at 414 US hospitals involving patients admitted with acute exacerbation of COPD in 2006 and 2007 to a non-intensive care setting and who received systemic corticosteroids during the first 2 hospital days.

Of 79,985 patients the study looked at, 73,765 were initially treated with intravenous steroids, whereas 6,220 received oral treatment. Of these, 1.4% of the intravenously treated and 1.0% of the orally treated patients died during hospitalization. In addition, the risk of treatment failure was lower among orally treated patients, as was the length of the patient’s hospital stay.

The study determined that lower, and therefore safer, doses are just as effective in treating COPD and also save about $500 per hospitalization. By this measure, U.S. hospitals could save a total of $250 million by treating COPD patients with orally taken low-dose corticosteroids.

Source: Patient Safety America Newsletter, August 2010. View it here.
You can view the study here.

For years, patient safety experts have known that medical devices, like tubes that deliver food and drugs to hospitalized patients, need to be designed so that predictable mix-ups don't hurt patients. If a tube is safe if it goes through the nose to deliver food to the stomach, it should not be possible to hook up the same tube to a line that delivers medication to a blood vessel, since that could kill the patient.

But this basic safety philosophy -- which permeates other high-risk industries like aviation and nuclear power -- still hasn't penetrated the medical industry, as a new report in the New York Times documents in distressing detail.

Partly to blame is the U.S. Food and Drug Administration, which could set up uniform rules that would bar as unsafe any medical devices where fatal mix-ups could be easily made by hurried nurses or other caregivers.

The way the agency does its work is the problem. When the FDA has tried to act on a case-by-case basis with an application from a manufacturer for a new product, efforts by FDA safety reviewers to solve the problem have been met with cries from the new manufacturer that it is being unfairly singled out.

Efforts to have industry-wide regulations have met with years of bureaucratic delay and industry resistance.

Here's a quotable quote from former FDA official Dr. Robert Smith:

“F.D.A. could fix this tubing problem tomorrow, but because the agency is so worried about making industry happy, people continue to die.”

Medical researchers are discovering that patients aren't quite as dumb and helpless about making intelligent and informed choices about medical treatments as many doctors have assumed over the years. Case in point: prescription drugs. Patients have proven their ability to make smart choices even in the face of complex pro and con information, as long as the data are presented in a straightforward way.

Click on this link to see a "Drug Facts" box on an important drug: Tamoxifen (nolvadex), which can help lower the risk of breast cancer, but with lots of competing risks and benefits. This is a sample, prepared by researchers at Dartmouth medical school, of the way that information ought to be presented on all prescription drugs. Note the clear presentation of the statistical likelihoods of being helped and harmed by Tamoxifen.

You don't see these Drug Facts boxes anywhere now. Instead, what we have now are ads to consumers that first show happy, healthy, bouncy people, presumably after they've taken the drug, along with a few simplistic sentences pushing the drug's benefits, but next these same ads show acres of fine print with all the downsides of the drug. The subliminal message is that all patients need to do is "ask your doctor" if Drug X is right for you. Meantime, your doctor has been sold a message on Drug X -- usually by a well-tailored, attractive sales rep -- that is only slightly less simplistic than the one in the "direct to consumer" advertisement.

So really, both patients AND doctors could benefit from a requirement that the drug information be reorganized and presented in an intelligible way. The FDA is now considering such a rule.

The Dartmouth researchers -- Lisa M. Schwartz, MD, Steven Woloshin, MD, and H. Gilbert Welch, MD, MPH -- have published a study proving that consumers presented the Drug Facts boxes for two competing drugs for prevention of heartburn, one of which was a lot more effective than the other, were a lot more likely to pick the correct drug when the information was presented more clearly. They also found that the consumers presented the standard advertisement tended to over-estimate the drugs' benefits in preventing disease -- no surprise there -- and that the Drug Facts box helped set them straight.

I've written before in this blog about tamoxifen. There was an interesting study that found that very few women chose to take tamoxifen once the pros and cons were fully laid out in an understandable way. In that study, and in my blog piece, the numbers were presented a little differently than the Drug Facts sample box. I used the "count the people" technique which is detailed in my book, "The Life You Save." This can make the numbers more graspable than the usual "percentages."

For example, if we consider a hypothetical 52-year-old woman who had her first baby after age 30 and whose mother had breast cancer, she has about a 1.9% risk of developing breast cancer over the next five years. (The risks of breast cancer vary with age, family history, and age of first childbirth.)

So if 1,000 women just like this 52-year-old took tamoxifen over those five years, the research says that here is what would happen:

* Of the nineteen women (same as 1.9%) who otherwise would have developed breast cancer, nine will not develop breast cancer.

* Thirteen women would avoid broken bones from osteoporosis, another benefit of tamoxifen.

* Twenty-one women would develop endometrial cancer (typically more treatable and less deadly than breast cancer if caught early).

* Twenty-one women would develop blood clots.

* Thirty-one women would develop cataracts.

* Twelve women would experience sexual problems.

* One hundred twenty extra women would get hot flashes and other menopausal symptoms (in addition to those who would get such symptoms anyway).

The researchers who wrote the study bemoaned this as an example of patients being unreasonably scared about shifting off their status quo (not taking the drug), but as I noted in my blog, a lot of patients who read the data in the New York Times and wrote comments on the Times' "Well" blog concluded that the women in the study who declined tamoxifen were just making reasonable choices for themselves.

The point is: There is no right or wrong answer when it comes to taking a drug over the long haul to prevent a disease. For some patients, it will be worth the downside of the drug. For others, it won't. But each of us is entitled to make an intelligent and informed choice, and that's why we need more clearly presented information than we're currently getting from the drug manufacturers.

If you don't have high cholesterol, but you do have a high level of inflammation in your blood, you are about to be targeted by a new marketing campaign for Crestor, the statin drug. You will be told the drug can lower heart attack risk by as much as 50 percent. Should you swallow this advice, and should you take a daily dose of these pills for the rest of your life?

The downside of statin pills is the possibility that they increase risk of diabetes and liver damage. The upside, of course, is reducing your risk of dying from the nation's No. 1 killer, heart disease. So it's important to know accurate numbers to make an intelligent decision.

The 50% reduction in heart attack is actually a statistical sleight of hand. The correct risk reduction number is actually around one in 500, or 0.2%. To understand the number manipulation involved, read on for a gentle short course in medical statistics.

These numbers come from a big study that the FDA used to give the green light to Crestor's new marketing campaign. The researchers found that around four in 1,000 patients with a high level of C-Reactive Protein (an inflammation marker in the blood) but with normal cholesterol had heart attacks if they took a dummy (placebo) pill in the study. Similar patients who took Crestor had a heart attack rate of around two in 1,000. These numbers come from the tail end of a new article in the New York Times on the FDA's approval of the new Crestor campaign.

Now the difference between four and two is 50 percent, but that conveniently leaves out the denominator in the statistic. The real risk reduction is from four in 1,000 to two in 1,000, or a difference of two in 1,000, which is the same as 0.2 percent. The 50 percent number is called the relative risk, and the 0.2 percent number is the absolute risk. Absolute risk is what measures real people and is the one we should focus on, but marketers like relative risk because it produces more dramatic numbers. Put another way, you can have statistically significant benefits from taking a drug on paper, but the clinically significant benefit, in real life, is much much smaller.

In my book, The Life You Save: Nine Steps to Finding the Best Medical Care -- and Avoiding the Worst, I discuss the Crestor story because it's just one example of how consumers can be misled by medical numbers. There's a straightforward solution, which I call "counting the people," when you are looking at any supposed medical breakthrough. Here's what I said in the book:

The real number [of how many patients benefit from a drug] might be enough to persuade some patients to take the drug. But it's a lot different than fifty percent. Bottom line: to make intelligent choices about treatments, patients need to understand how many patients like them are really expected to benefit from the treatment. You can get these answers by focusing on how many actual people are helped by the treatment. Do not focus on misleading vague numbers like “50 percent improvement.” Fifty percent of what? Focusing on real numbers of real people will give you the answer.

As a patient safety advocate, I want all smart consumers of health care to know at least a little bit about statistics -- because the real numbers can be very eye-opening.

The free meals, trinkets and other goodies now lavished on doctors by the prescription drug industry will soon be a matter of public record for each doctor in the United States, under a provision of the new health care reform law. A searchable database goes into effect in 2013 that will let anyone plug in a doctor's name and find out how much largesse that doctor received in the past year. This is a positive development for patient safety in the United States.

Readers of this blog know from past reports that even small "gifts" from manufacturers are highly effective in influencing doctors' prescription writing habits. The industry spends about $1 billion a year in free meals for doctors and many more dollars in countless free pens, scratch pads, textbooks and other trinkets branded with the names of various drugs being promoted. (As we reported in another post, deep-sea fishing trips and golf junkets are also part of the blandishments.)

Do small gifts matter? Yes, as the Pew Prescription Project points out in an excellent fact sheet that summarizes the studies on how doctors' decisions about drugs are influenced by manufacturers. As the Pew researchers write:

[T]he evidence is clear: gifts, even small ones, change behavior. Such marketing drives up drug costs and sometimes puts patients at risk. Social science research ... shows that a gift of any size imposes on the recipient a sense of indebtedness. This need for reciprocity is a deep-seated human reaction. It creates in the recipient, whether consciously or not, a sense of obligation to repay favors, gifts, invitations, etc. Research shows that it takes extraordinarily little to bias an individual’s interpretation and processing of information. Such bias is both subtle and unintentional.

Now, that's "subtle and unintentional" bias on the part of the doctor receiving the gift. Most doctors will deny heatedly -- and honestly -- that drug freebies have any role in how they prescribe medicines. The manufacturers, who study this closely, know otherwise. There is nothing "unintentional" about the way they spend money on seemingly innocuous trinkets like pens.

The new reporting law requires the drug manufacturers to report to the government everything of value given to any doctor or teaching hospital, starting January 1, 2012 (and the government web site has to be up by September 30, 2013).

Manufacturers do not have to report gifts worth less than $10, but if the total of those gifts in one year to any doctor reaches $100, then all gifts have to be reported. There are a few other exemptions and other details worth reading in this "Sunshine" fact sheet from Pew.

Free samples of drugs also will be covered by another part of the law. As I have reported before, thoughtful doctors don't even accept free samples because that can bias their prescriptions away from "tried-and-true" medicines toward newer drugs with uncertain safety records.

I have a chapter in my book, The Life You Save: Nine Steps to Finding the Best Medical Care -- and Avoiding the Worst, educating consumers on how to use prescription drugs safely. One of my key points is that people need to realize that the first few years a new drug is on the market -- during the time of its heaviest promotion by the manufacturer -- is also the most dangerous time for the patient to try the drug, because early users are basically guinea pigs.

This new law infringes no doctor's freedom to accept gifts from industry, and doesn't impact any patient's freedom to patronize such doctors. But with education and "sunshine" about how these gifts create conflicts of interest for the doctor, we can hope that the torrent of freebies will start to slow. All patients will be better off if the education doctors get about new drugs is not influenced by industry gifts.

The FDA says it is re-investigating the issue of whether drugs like Fosamax, which are given to post-menopausal women, can actually cause fractures of the thigh bone (femur).

A number of lawsuits are pending about death of jaw bone tissue allegedly caused by this family of drugs, called biophosphonates.

Previously the FDA said it had seen no link between these drugs and femur fractures. But new studies reported at the annual meeting of the American Academy of Orthopaedic Surgeons raised questions about the risks for long-term use of bisphosphonates by post-menopausal women.

The FDA says it will consult with outside experts. Meantime, it says people on the medications should continue taking them but should talk to their doctors if get any new hip or thigh pain. See the FDA's news release here.

Bisphosphonates have combined annual sales topping $3.5 billion. In addition to Fosamax, drugs in the group includes Actonel marketed by Sanofi-Aventis and Procter & Gamble, Boniva marketed by Roche and GlaxoSmithKline, Novartis’s Reclast and P&G’s Actonel.

New ethics rules that bar Harvard doctors from giving speeches paid by drug manufacturers have prompted one doctor to give up his prestigious academic position in favor of keeping the income from the speeches. The physician is Dr. Lawrence M. DuBuske, an allergy and asthma specialist who is quitting his positions at Boston's Brigham and Women’s Hospital and Harvard Medical School. According to the Boston Globe, Dr. DuBuske made about $100,000 in three months last year giving some 40 speeches for six drug makers, including GlaxoSmithKline.

The ethics rules were put in place by Partners HealthCare, the physicians' group that employs most Harvard-connected doctors.

One Globe reader put this in a good perspective:

It's a good thing that he resigned. Now, when he speaks, the information he presents will be judged by the standards of a paid speaker employed by an entity with interests, rather than a disinterested academic. Meanwhile, he remains an expert allergist, and will likely find a place to practice.

The contacts between drug companies and academic medicine are extensive. They should be. You want the best, smartest, most creative docs involved in drug (and device) production. But the money involved is huge, and some will get seduced by the Green Side of the Force. Full disclosure of interests is a step, but only a step.

For patients, it helps to know if the prescription the doctor is writing for you has even a hint of a special interest from the drug maker. The many blandishments that drug makers lavish on doctors -- even small things like pens and scratch pads, plus free meals and "fees" for speaking at seminars -- are known to do their job of creating subtle influence on the prescription writer.

That's why I recommend that patients look for doctors who have the "no free lunch" philosophy: they accept nothing whatsoever, including samples, from the drug makers. That leaves their judgment completely independent.

You can read more about the "no free lunch" movement in medicine at this website.

I have a whole chapter in my book, "The Life You Save," on how to become a smart consumer of medicines.

In a logically designed drug safety system, data from new studies would automatically be pooled so that as more and more patients take a drug, researchers can see potential harms across all the data at one time, rather than looking at individual research studies in isolation. Alas, that is not our world.

A new proposal would change that, but it would take an act of Congress to do so.

As described in the Archives of Internal Medicine, a group of researchers analyzed all the studies published on Merck's anti-arthritis drug Vioxx to see when the risk of heart attack could have first been identified. The drug was first put on the market in 1999 and was taken off the market in September 2004 when Merck said it first realized there were many heart attacks in patients taking it.

The researchers led by Joseph Ross, M.D., now say that their analysis, pooling data from 30 separate clinical trials, shows there was statistically significant increase in heart attacks in Vioxx patients as early as June 2001, three years before the drug was removed from pharmacy shelves. The studies after 2001 only strengthened the statistical association, they say.

If we had a system in place that automatically pooled all safety data on drugs as new studies are published, many safety risks could be identified much sooner.

But the head of drug safety at the Food and Drug Administration, Dr. Janet Woodcock, said Congress would have to authorize a change in the existing monitoring system to make for these automatic updates. Currently, she told the New York Times, the FDA does such combined-study reviews but only when a particular drug catches the eye of FDA safety officers.

Consumers are well advised to hold off on taking new drugs until they have been on the market for seven years. This is the advice I give in my book, The Life You Save: Nine Steps to Finding the Best Medical Care -- and Avoiding the Worst.

Seven years is enough time for safety experts to see whether the new drug has enough benefits that outweigh its harms. In theory, the approval by the FDA to let a drug be sold should provide that green light, but before a drug is approved, only a few thousand patients typically are studied, while many hundreds of thousands will take a drug in the years after approval.

The new study by Dr. Ross and colleagues is yet another example of how far we have to travel before consumers can be assured that a brand new drug is right for them.

Most doctors have to take regular continuing education courses to maintain their medical licenses. But what if the courses have a hidden agenda -- promoting the drugs of a sponsoring manufacturer?

That hidden influence has occurred far too often for the comfort of patient safety advocates, who want prescribing doctors to receive fair, balanced and neutral advice in the important subject of what prescriptions to write for sick patients.

Now the group that gives the official seal of approval for continuing education courses is taking tentative steps to curb the drug industry's influence on these courses. The group is called the Accreditation Council for Continuing Medical Education (ACCME). Its approval is necessary for a doctor to get official credit for any course taken. The head of the ACCME, Dr. Murray Kopelow, told the New York Times he will:

First, make public in the next few weeks a list of the classes and educational companies that have already been found to have broken the rules against commercial bias. This list was previously secret. Apparently there are less than a dozen names on the list as of now.

Second, consider further steps such as requiring the sponsor of a course found to be biased to send out corrective material to the doctors who took the course.

A doctor who is pushing for these and stronger reforms is Dr. Bernard Carroll, who filed a lengthy complaint about an online course on treatment of major depression, which he said was strongly biased by hiding bad information about the drugs of the sponsor, AstraZeneca.

The Times reported:

Dr. Carroll faulted the accrediting council for taking nine months to resolve the complaint, allowing the program to rerun and failing to notify doctors who had taken it. “They’re more interested in protecting the providers than watching what gets put out there as education,” Dr. Carroll said in an interview.

Here is Dr. Carroll's own blog posting on the subject.

The steps taken so far by the accrediting body are modest, but go in the right direction. Let's keep watching. As another industry critic, Dr. Bernard Lo, said, it's okay for the drug industry to support medical education. What's not okay is to create commercial bias in favor of one or another company's products.

A few brave medical journal editors are cracking down on the common practice of drug companies ghost-writing articles for authors who are willing to lend their names to drug industry propaganda. But at other journals, editors seem to have a "don't ask, don't tell" policy. For patients, it is vital that the truth come out.

The problem with ghost-written medical articles is that they purport to be something that -- once the disclosure of who wrote them is made -- they clearly are not: independent, objective evaluations of which medications work best for a particular disease. Instead, the ghosted articles turn out to be elaborate infomercials, disguised by the author's prestigious name and studded with multiple footnotes and the other signs of scholarly elbow grease. Yet because they are published under false pretenses, these articles can be very effective at selling their sponsors' products.

What first broke open this scandal was lawsuits against Wyeth for breast cancer and other injuries caused by its hormone drugs Prempro and Premarin. Attorneys for the patients found multiple examples in the manufacturer's records of prominent medical researchers putting their names on articles written by someone hired by the drug company.

Some of the medical school professors who were caught tried to brazen their way out of it by saying that of course, they wouldn't put their name on something they didn't agree with, and they just happened to agree with every single word that was written for them. For example:

Dr. Gloria Bachmann of the Robert Wood Johnson School of Medicine said in a published report: “This is my work, this is what I believe, this is reflective of my view.”

With shameless attitudes like that rife in the medical academic world, it's important for the editors who control what goes into the journals to step up and enforce some accountability. The first steps down that road have been cautious at best. As the New York Times reported:

Dr. Cynthia E. Dunbar, the editor in chief of Blood, said that, in the future, the journal would consider a ban of several years for authors caught lying about ghostwriting, in addition to retracting their ghosted articles.

But, said Dr. Dunbar, who is a hematologist at the National Institutes of Health in Bethesda, “I hope we don’t have to do that.”

The Times reported on another journal that took a stand:

In an editorial last week calling for a zero tolerance policy, the editors of the medical journal PLoS Medicine, from the Public Library of Science, called for journals to identify and retract ghostwritten articles and banish their authors.

“Any papers where this breach is substantiated should be immediately retracted,” the editors wrote. “Authors found to have not declared such interest should be banned from any subsequent publication in the journal and their misconduct reported to their institutions.”

Click here to read the full editorial.

Other journal editors told the Times that because they banned ghostwriting, they didn't really have to have a specific policy enforcing the ban. Huh???

For an amusingly arch, tell-it-like-it-is take about medical ghostwriting from someone outside the medical industry, I recommend English professor Margaret Soltan's blog, University Diaries.

The ghostwriting scandal, and the cautious, tepid response from many in the medical journal world, are the latest proof of why I advocate that patients be skeptical about prescription drugs, especially those with expensive marketing campaigns behind them. Read more in Chapter 7 of my book, "The Life You Save: Nine Steps to Finding the Best Medical Care -- and Avoiding the Worst." The chapter is titled: "Drugs: A Dose of Reality About the Prescription Drug Industry and How You Can Safely Use Medicines."

A lawsuit by the state of South Carolina has turned up evidence that one sales representative for Eli Lilly bet golf scores with a doctor client -- and the payoff was the doctor's agreement to write more prescriptions for the drug Zyprexa.

According to an article by Bloomberg News, notes from this and other sales reps showed attempts to get the doctors to prescribe Zyprexa for "off-label" uses -- those for which the manufacturer had not shown evidence to the FDA that the drug was safe and effective.

The state is trying to get a court to force Eli Lilly to refund excessive spending in the state Medicaid program on Zyprexa prescriptions. Lilly has settled one state lawsuit from Alaska and also agreed to a U.S. Justice Department settlement that involved thirty other states.

The inducements to doctors to prescribe the powerful antipsychotic drug included deep-sea fishing trips and speaker fees for those doctors who would address meetings of their colleagues, according to the suit.

This is yet another example of why I urge patients to be skeptical about drugs and to try to find a primary care doctor who doesn't take freebies from drug manufacturers. Even the most innocuous of handouts from drug companies can influence how a doctor writes prescriptions. Read more about this in my book, "The Life You Save: Nine Steps to Finding the Best Medical Care -- and Avoiding the Worst."

Another reason for careful patients to be skeptical about overly hyped prescription drugs came this week with news about the extent to which articles in important medical journals are "ghost-written" by drug manufacturers.

According to an article in the New York Times by Natasha Singer, newly released papers from lawsuits involving Wyeth's hormone replacement drugs Premarin and Prempro show that over several years, Wyeth repeatedly hired ghost writers who placed 26 articles in 18 prestigious medical journals, all promoting the drugs in the guise of objective analysis by medical experts:

The court documents provide a detailed paper trail showing how Wyeth contracted with a medical communications company to outline articles, draft them and then solicit top physicians to sign their names, even though many of the doctors contributed little or no writing. The documents suggest the practice went well beyond the case of Wyeth and hormone therapy, involving numerous drugs from other pharmaceutical companies.

The Times article made an interesting comparison to professional baseball's steroids scandal.

“It’s almost like steroids and baseball,” said Dr. Joseph S. Ross, an assistant professor of geriatrics at Mount Sinai School of Medicine in New York, who has conducted research on ghostwriting. “You don’t know who was using and who wasn’t; you don’t know which articles are tainted and which aren’t.”

Because physicians rely on medical literature, the concern about ghostwriting is that doctors might change their prescribing habits after reading certain articles, unaware they were commissioned by a drug company.

“The filter is missing when the reader does not know that the germ of an article came from the manufacturer,” said James Szaller, a lawyer in Cleveland who has spent four years going through the ghostwriting documents on behalf of hormone therapy plaintiffs.

The same concern about ghostwriting applies to patients who read literature on the Internet. People can be easily misled if they think an article is truly objective.

My advice, as I write in my book, "The Life You Save," is to rely on truly independent groups like the Medical Letter and Public Citizen's Health Research Group for objective information about drugs.

Some top medical journals like the Journal of the AMA now require authors to fill out detailed forms describing exactly how much input they had into the writing of an article. But many do not have such requirements. Consumer, beware.

They seem so benign -- those free samples of prescription drugs in bubble packs that your doctor hands out at the end of an office visit. But there are plenty of hidden costs in free samples, and two prominent doctors have written an essay asking that the pharmaceutical industry stop the $15 billion a year practice of what is called "sampling." In an article by Susan Chimonas and Jerome Kassirer (former top editor at the New England Journal of Medicine), they write:

The samples that drug representatives offer are almost never time-worn and well-tested drugs, nearly never generics, and usually comprise the newest agents on the market. As such, they expose patients to risks not yet identified in clinical trials. The experience with Vioxx is a case in point. By 2002, only three years after Vioxx was introduced, it became the most widely distributed sample [3], and two years later the drug was withdrawn from the market because of an excess risk of myocardial infarctions and strokes [9]. Needless to say, Vioxx was not the only drug given extensively as samples and later found to enhance risk. Samples given to pediatric patients have similarly been associated with notable safety concerns. In 2004, four of the 15 medications most frequently given as samples to children in the US received new or revised “black box” warnings from the US Food and Drug Administration within two years of approval [10]. Finally, patients may not be the only ones at risk from distribution of free samples. Physicians who offer samples to patients and fail to supply appropriate cautions and warnings about the use of these drugs may be subject to liability, along with the company that promoted the drug [11].

There are plenty of other problems with "sampling." It encourages casual use and misuse of potent drugs. It doesn't really help indigent people get affordable medications. It bypasses the pharmacist, who provides user-friendly educational pamphlets that can alert patients to potential problems with the drug.

The authors conclude:

The tradition of physicians dispensing samples has many serious disadvantages and is as anachronistic as bloodletting and high colonic irrigations. As the profession begins to slowly extract itself from the influential grip of industry, it must also deal with the undue influence of free samples.

The article is also reprinted in Public Citizen's "Worst Pills, Best Pills" newsletter.

In Chapter 7 of my new book on health care, The Life You Save: Nine Steps to Finding the Best Medical Care -- and Avoiding the Worst, I discuss the idea that safe and wise use of prescription drugs includes not taking a drug during its first five to seven years on the market. That's because the real hazards of a new drug are not well known until it has been widely used. For the same reason, it's a good idea to avoid free samples, which usually are newer drugs that don't have the safety track record of established drugs. The only exception is for "breakthrough" drugs that truly offer treatment where no drug was available before.

The recent news that an FDA advisory panel has proposed that Vicodin and Percocet be taken off the market because of their acetaminophen content has prompted a discussion about the overall safety of this drug, which is best known as Tylenol and is present in a number of both prescription and over-the-counter pain drugs.

The New York Times' Tara Parker-Pope had a good summary in her Well blog, in which she said acetaminophen is generally safe when taken within the maximum dosing guidelines of no more than four grams -- 4,000 milligrams or 8 extra-strength tablets -- per day. But there is one big exception that she didn't discuss: for people who regularly drink alcohol, the daily limit of acetaminophen should be much lower. I explained this in a comment to her blog entry. Here is the text of what I posted:

The link between acetaminophen and alcohol deserves to be clarified because it is not that straightforward but is actually pretty easy to understand. Regular alcohol drinking “induces” a metabolic pathway in the liver called P-450 2E1, making the liver more efficient at breaking down alcohol with this 2E1 enzyme. This happens within a few days of drinking 2 or 3 or 4 drinks a day. That’s why steady drinkers can “hold” their liquor better, because they are breaking it down faster and so less alcohol gets in the blood. When you stop drinking for a few days, the liver reverts back to its old self and so the first time you drink again, your liver is less efficient at breaking down the alcohol so you get a “buzz” with the first drink. Here’s how this relates to acetaminophen: The same 2E1 enzyme turns acetaminophen into the toxic byproduct (called NAPQI) that can destroy the liver. So regular drinking produces more 2E1 and hence more NAPQI, and the more acetaminophen you take, the more the NAPQI can overwhelm the liver’s other defense mechanisms and cause liver cell death. But here’s the twist: drinking alcohol at the same time as you take acetaminophen puts both drugs into the liver at the same time, competing for the same 2E1, and thus drinking at the same time actually can protect against liver damage. The deadly pattern is when a drinker gets sick, with the flu for instance, stops drinking and starts taking acetaminophen near the maximum 4 grams a day, and that can cause catastrophic liver failure (because the 2E1 has nothing else to do but turn the acetaminophen into the NAPQI). I know about this because as a lawyer I represented a number of Tylenol victims in lawsuits in the mid-1990s that helped get the alcohol warning onto acetaminophen labels. I took many depositions of the medical people at McNeil, the Tylenol manufacturer.

Anyone who drinks regularly should take no more than 2 grams of acetaminophen a day. Any liver specialist will tell you that.

I talk about what I call the safe and skeptical approach to taking medicines in my new book: “The Life You Save: Nine Steps to Finding the Best Medical Care — and Avoiding the Worst.”

At the annual conference of the American Society of Clinical Oncology, scientists presented a new study that found certain antidepressants may interfere with the effectiveness of tamoxifen, a drug commonly taken by breast cancer survivors to keep the cancer from coming back, according to an Atlanta Journal-Constitution article.

Tamoxifen has been used for decades to treat breast cancer and, for the survivors, to prevent tumors from forming again. One of the most common side effects of tamoxifen is hot flashes, which can be controlled by SSRI (selective serotonin reuptake inhibitor) antidepressants such as Paxil and Prozac. The new study shows that this cocktail of drugs seems to account for a higher recurrence rate of breast cancer. The study followed almost 1,500 women whose average age was in the early 50s. Researchers found that women who took both tamoxifen and the SSRI antidepressants were almost twice as likely to have their breast cancer return within two years.

At the same ASCO conference, another paper was presented that found no correlation between breast cancer recurrence rate and use of antidepressants. However, authors of this second study pointed out that this study included a much smaller pool of subjects, and they join authors of the first study in recommending that other options should be considered to treat hot flashes.

Stroke experts have widened the window for when the clot-busting drug tPA can be given intravenously. The previous U.S. guideline was to give the drug only if treatment could be started within three hours of the onset of symptoms. Many patients did not get the drug because they didn't get to the hospital in time or it took too long to do tests to make sure the drug could be helpful. (Everyone with stroke symptoms has to have a CT scan to make sure the stroke is not caused by bleeding in the brain, because if tPA is given on top of bleeding, it could worsen the hemorrhage or even kill the patient.)

The new guideline widens the effective time window to four and one-half hours after symptoms start. It comes from the American Heart Association/American Stroke Association and is based on European studies.

Stroke experts stress that just because there is more time now to administer this drug does not mean patients or doctors should think they can go slow. The faster treatment is begun, the more likely it is to help break up the clot and restore normal blood flow in the brain. Anyone with stroke symptoms needs to be rushed to a hospital with special expertise in stroke treatment.

Acetaminophen, the unpronounceable name for the active ingredient in Tylenol, is the most widely used pain reliever in the United States. But it can destroy the liver in ordinary or near-ordinary doses. That fact is news to many consumers but is old hat to liver specialists who every week treat patients at death's door from acute liver failure due to acetaminophen.

It has now been documented that acetaminophen is the most common cause in the U.S. of acute liver failure, which can result in death if a liver transplant cannot be done.

The Food and Drug Administration has recognized that acetaminophen poisoning is a public health issue and has slowly taken steps to educate the public to this popular drug's dangers. In April 2009, the FDA mandated a new warning label, which will say on 500-mg products (Extra Strength Tylenol and its generic equivalents): “Liver warning: This product contains acetaminophen. Severe liver damage may occur if you take more than eight tablets in 24 hours, the maximum daily amount.” It will also warn against using it with other acetaminophen products or with alcohol use of three or more drinks a day. The FDA rejected a request from the Tylenol manufacturer McNeil to water down the warning by removing the word “severe” and adding the word “overdose,” which the agency said could lead consumers to believe they had to greatly exceed the recommended dosage before jeopardizing their livers.

This warning won't take effect until spring 2010. FDA advisors first recommended such a liver warning in 1977.

In the meantime, an FDA advisory panel will meet in late June to consider other steps intended to make it harder to accidentally cause liver failure from taking too much acetaminophen. A "working group" of advisors has recommended among other things:

• limiting the single adult dose to a maximum of 650 mg, and limiting tablet size to 325 mg (down from the current extra-strength size of 500 mg and single dose of 1000 mg);
• lowering the maximum daily dose for adults from 4000 mg to no greater than 3250 mg (and less than that for chronic alcohol users);
• restricting pediatric liquid formulations to a single mid-strength concentration;
• eliminating acetaminophen from combination products.

You can read the working group's recommendations at the FDA's web site here.

In the 1990s, Patrick Malone was one of the first attorneys in the United States to successfully sue the Tylenol manufacturer for hiding the dangers of acetaminophen from doctors and the public. Read about his case of Benedi v. McNeil here. Watch the ABC Prime Time Live segment on this subject by clicking here.

Starting July 1, Vermont residents will be able to learn exactly how much money any doctor in that state is receiving from the drug and medical device industry. The state is also banning most gifts like free meals to doctors, nurses, pharmacists and other health care providers.

This is an important step forward in eliminating the conflicts of interest that plague use of prescription drugs in the United States.

Vermont already has publicized non-doctor-specific data on drug industry payments intended to influence doctors. Even in a small state like Vermont, the total spent last year was $2.9 million, with most of the money targeted to doctors thought to be influential with their peers. The biggest single payment was $112,000 to a psychiatrist. And the drugs which topped the list for money paid were Strattera, a drug for attention deficit disorder, and Cymbalta, for depression and anxiety.

The new legislation was reported in an article by Natasha Singer in the New York Times.

Doctors and drug companies often deny that free meals and payments of consulting fees have any influence on doctors' prescribing habits. The mere fact that the industry spends hundreds of millions of dollars each year on such marketing suggests otherwise. Commendably, the Vermont Medical Society supported the new disclosure law.

Patrick Malone discusses conflicts of interest and how patients can use drugs -- sensibly, skeptically and safely -- in his new book: The Life You Save: Nine Steps to Finding the Best Medical Care -- and Avoiding the Worst.

One day after the FDA approved a new antiwrinkle drug (Dysport) in April 2009, the agency issued a new requirement that these drugs must carry a “black-box” warning label, the strongest safety warning typically reserved for drugs with very serious risks, Natasha Singer reports in a New York Times story. A popular antiwrinkle drug in the U.S. is Botox.

Botox and Dysport are injectable drugs developed from botulinum toxins, which temporarily paralyze the muscle into which they are injected. When administered for approved uses at approved doses, the botulinum toxins cause no harm. However, if used improperly, the toxins can travel from the injection site to other parts of the body, causing difficulty with swallowing or breathing.

Approved uses of injectable botulinum toxins include treatments for crossed eyes, eyelid spasms, severe underarm sweating, frown lines, and cervical dystonia, a neck problem that can cause severe pain and abnormal head position.

According to the new FDA requirement, the drug manufacturers not only have to add the black-box warning labels, they also have to inform doctors of the risk information in writing, and make available a medication guide to patients at the time of injection.

Patients are well advised to read all handouts on drugs they take, especially something used for cosmetic purposes. Every drug has risks and must be taken with caution.

Ten rules for safer drug use can be found at Public Citizen's Health Research Group website. These rules and more tips for safe drug use are discussed by Patrick Malone in his book, The Life You Save: Nine Steps to Finding the Best Medical Care -- and Avoiding the Worst.

Strokes cause more disability than just about any other disease, but they don't have to. Effective treatments are known for the most common type of stroke; delivering them to the right patients has proven to be difficult. Now a group of researchers is proposing some changes in how stroke care is organized, with the hope of matching reality to the promise and greatly improving stroke outcomes.

In 1995, a landmark study was published showing that the impact of stroke on the human brain could be greatly diminished by using clot-busting drugs to dissolve the clots that kill brain cells in ischemic stroke. (Ischemic stroke is responsible for about four of five strokes. In ischemic stroke, brain tissue dies because blood clots or narrowed blood vessels block flow of oxygen-rich blood to brain tissue. In hemorrhagic stroke, which affects about one in five stroke patients, brain tissue dies because a burst blood vessel causes bleeding in the tissue.)

Today, though, it is estimated that fewer than one in ten victims of ischemic stroke are treated with either intravenous tPA, the main clot-dissolving drug, or other effective treatments, such as breaking up the clot with a mechanical device inserted inside the blood vessel.

The accepted convention is that tPA does not work unless the i.v. is started within three hours of the onset of stroke symptoms. Most patients don't get to the hospital that quickly, and even when they do, time is eaten up by the necessity to give everyone a CT scan to make sure they are not having a bleeding stroke, for which use of the clot-dissolving drugs could be a disaster.

A new article by Drs. Reza Hakimelahi and R. Gilberto González, "Neuroimaging of Ischemic Stroke With CT and MRI: Advancing Towards Physiology-Based Diagnosis and Therapy," advocates these changes to help deliver more of these proven treatments to more patients:

* Doctors need to recognize that the three-hour window for treatment sometimes is much longer in patients who have blockages of smaller vessels in the brain with some temporary compensation through "collateral" vessels. Better imaging studies can identify these patients who have an "ischemic penumbra" that would benefit from clot-dissolving drugs.

* Many patients can benefit, even after the three hours has expired, by direct intervention with mechanical devices to break up clots from the inside of the vessels. Because this requires expertise in interventional neuroradiology, a field with only a few hundred practitioners in the United States, the authors recommend cross-training for doctors in related fields who know how to use tiny tubes inside blood vessels to deliver treatments. These include interventional cardiologists.

* Hospitals that are recognized as expert in care of acute strokes could be divided between advanced and general levels of expertise. On the general level, any such hospital needs to have 24-hour CT scanning and the ability to give clot-busting drugs in the emergency department. To qualify as an advanced stroke center, the hospital would have to have the ability to do interventional treatments inside blood vessels ("endovascular therapy"), a neuro-intensive care unit, and a team of doctors from multiple specialties that work together to decide the best treatment for each patient.

(NOTE: To read this article, you have to sign up for a free membership at Medscape.com.)

As these ideas are debated in the medical industry, the best strategy for patients is to have some advance knowledge and basic planning. Knowing how common strokes are, and how urgent the timeline is ("Time Is Brain" in stroke treatment) once stroke symptoms start, here is what I advocate:

* Know the basic symptoms of stroke, and don't rationalize your way out of a trip to the hospital if the symptoms seem mild or go away after a few minutes. Here is a basic list from the American Stroke Association:
* Sudden numbness or weakness of the face, arm or leg, especially on one side of the body
* Sudden confusion, trouble speaking or understanding
* Sudden trouble seeing in one or both eyes
* Sudden trouble walking, dizziness, loss of balance or coordination
* Sudden, severe headache with no known cause

* Know which hospital in your area has advanced stroke treatment staff and machines. Ask if they have a multi-disciplinary team. (It should include both neurosurgeons and endovascular therapists.) Ask if they have a neuro-intensive care unit (an ICU that treats only patients with brain or spinal cord problems).

* If a loved one suffers stroke symptoms, do not let the rescue squad take them to the nearest emergency room UNLESS the same hospital has advanced stroke treatment abilities.

* A multi-disciplinary team is important because conflicts of interest can drive doctors to advocate for therapy they can do when a safer, more effective treatment might be available from a doctor with different training. Having doctors work together to help the patient and family decide treatment is the best approach.

In his new book, The Life You Save: Nine Steps to Finding the Best Medical Care -- and Avoiding the Worst, Patrick Malone discusses one tragic case in which a patient needed a teamwork approach to her neurological problem but didn't get it because the hospital had no effective team in place. The book discusses the questions to ask to make sure your doctors are working together and not as competitors for your health care business.

An Institute of Medicine report released on April 28, 2009, denounces the adverse effects that the health care system suffers from the free gifts regularly pumped into hospitals, medical schools, and doctors’ offices, writes New York Times’ Gardiner Harris. The report strongly advises doctors to stop accepting the gifts. The report says that accepting gifts would “create conflicts of interest, threaten the integrity of their missions and their reputations, and put public trust in jeopardy.”

When doctors accept gifts from drug companies – which may be money, drug samples, office supplies or food – they change their prescribing habits. This change may or may not be conscious, but the “reciprocity instinct” that prompts people to return a favor is part of human nature that has been recognized by psychologists and anthropologists. And when this happens, the patients are the real victims: their doctors may prescribe new drugs that are yet to be tested for their safety or effectiveness, or drugs that patients can easily replace with diet or lifestyle changes.

In his new book, The Life You Save: Nine Steps to Finding the Best Medical Care – and Avoiding the Worst, Patrick Malone discusses steps patients can take to avoid being victims of such conflicts of interest. He also explains how an average patient can dissect statistics on drug performance to determine if a particular drug is really as effective as it’s marketed to be.

In its letters sent to 14 pharmaceutical companies in March 2009, FDA required risk information to be included in the Internet search advertisements of drugs – a move welcomed by consumer advocates, reports Stephanie Clifford in a New York Times story.

The short text ads that appear to the right of Google search results are limited to 95 characters, in which space pharmaceutical companies are now required to include not only the drug’s name but also its risk information. Although the drug companies had made risk information available just one click away from the search ads, which linked to a webpage containing detailed information of the drugs including side effects, the FDA issued this new requirement to ensure consumers are not misled.

Rita Chappelle of the FDA said in an NYT interview that it’s “vital and critical” that consumers do not mistakenly believe the drugs to be safer or more effective than they really are. This precaution is especially important in drugs that have frequently occurring or serious side effects, such as depression, liver damage, infections or severe allergic reactions.

Blood clots that develop in the large veins of the calf can kill if they break off and travel up to the heart. That's what is called a pulmonary embolism, the killer of some 100,000 Americans every year. Now there's evidence that statin drugs for lowering cholesterol, and thereby preventing clogging of the arteries in the heart (thus lowering heart attack risk), may also lower the risk of clots developing in the veins, and dramatically so.

But don't demand a statin drug prescription from your internist just yet. You have to understand your own statistical risk first.

According to a major study of 18,000 patients, as reported in the New York Times, the patients who took the potent statin drug Crestor (rosuvastatin) had a 43 percent lower risk of blood clots in the leg veins than patients who took a placebo pill in the same study.

That's an impressive number. But more revealing, perhaps, is the actual number of patients that percentage represents. In the 18,000 patients, only 94 developed blood clots -- 34 in the group taking Crestor and 60 in those taking the dummy pill, thus the 43 percent difference. But the overall risk is so small that no responsible doctor would recommend people take a statin drug long-term to prevent blood clots in the legs, UNLESS you have some specific high risk for such blood clots -- such as a history of having them in the past.

This blog has made a similar point with other "breakthrough" reports on drugs -- actually on the same study with the same drug, when it reported in late 2008 that Crestor might reduce heart attack risk even in patients without high cholesterol. You have to count the actual numbers of patients affected and understand where you fit, before you can make an intelligent commitment to long-term use of a drug. This issue is discussed in more depth in my book, The Life You Save: Nine Steps to Finding the Best Medical Care -- and Avoiding the Worst.

Never underestimate the ingenuity of the pharmaceutical industry in promoting its products to the American public. The latest example: The "Real Age" questionnaire that millions of people have filled out on the Internet, to tell them if their "real age," based on lifestyle and family history, is younger or older than their chronological age.

It turns out that the company that sponsors the Real Age web site sells to pharmaceutical companies the detailed information it receives from patients who fill out the 150 questions in its survey. The actual names and email addresses of patients do not get transmitted to the drug companies, but Real Age sends emails to patients on behalf of the drug companies, and these emails are targeted to what a drug company thinks that patient might be interested in, based on the patient's responses to the Real Age questions.

All this happens, according to a report by Stephanie Clifford in the New York Times, whenever a patient clicks "yes" to the multiple opportunities offered during the Real Age questionnaire to "become a member" of the Real Age community. Once a patient says yes to membership, his information becomes part of a database that is then combed to see what pharmaceutical drugs might appeal to the patient.

"It's free," as the Real Age web site keeps reminding people.

But is it really? Patients who are drawn toward a drug by "direct to consumer" pitches like this are likely to sign on for a prescription they may not really need, and every prescription drug carries side effects that may outweigh the drug's benefits. In the early years of a drug's marketing, when manufacturers are most keen on pushing their products, the risks are not fully known to the medical community. That's because the studies done on drugs to win FDA approval are usually limited to a few thousand carefully selected patients.

The safest approach to using prescription drugs is explored by Patrick Malone in his new book, The Life You Save. See chapter 7.

The U.S. Supreme Court has rejected a strong push by the pharmaceutical industry to win immunity from lawsuits filed by injured plaintiffs. In a 6-3 decision in the case of Wyeth v. Levine, the Supreme Court ruled that the Food and Drug Administration's approval of a drug's label does not mean that the manufacturer has no obligation to improve the warnings on the label if new information comes to the attention of the manufacturer.

This is a big victory for patient safety. The case will help doctors too, by keeping the pressure on the drug manufacturers to keep their product labels up-to-date so that doctors can be educated about the safest way to use drugs. Medical leaders, such as a group of editors of the New England Journal of Medicine, had filed "friends of the court" briefs urging the Supreme Court to take the side of the injured patient.

The heroic patient who pushed this case was Diana Levine, a Vermont musician who lost her arm and her career after being injected too rapidly with an anti-nausea drug called Phenergan. The drug is well known to cause terrible injuries if it gets into an artery. She contended, and the jury and the Vermont Supreme Court agreed, that the drug's manufacturer, Wyeth, knew about this risk and should have warned doctors on the label to avoid the "i.v. push" technique that carried a high risk of inadvertent injection into an artery.

In a recent initiative against contaminated weight-loss products, the FDA finds 69 drugs to be contaminated with prescription drugs and chemicals, and expects the list of brands to grow even longer in the next few weeks, reports Natasha Singer of the New York Times. A complete list of the tainted drugs found so far is available on FDA’s website.

One of the best known drugs on FDA’s list is StarCaps, endorsed by many celebrities, which was found to be tainted with bumentanide, a powerful diuretic that can give rise to serious side effects. FDA’s Michael Levy said that many of the products “either contain dangerous undeclared ingredients or…have no effect at all.”

These weight-loss products are not only illegal – FDA considers a supplement unapproved if it contains an undeclared active pharmaceutical ingredient – they also pose dangerous risks for consumers. For one thing, the ingredients on their own can cause problems like elevated blood pressure or seizures. Worse, the hidden ingredients can have toxic interactions with other medications, making it difficult for doctors to diagnose patients or manage their illnesses.

Although many of the distributors of these 69 drugs have voluntarily recalled the products, others continue to sell them on the internet. Consumers taking weight-loss supplements should monitor FDA’s growing list of products they should avoid and consult their doctors for a healthy and safe weight management plan.

Seroquel is an atypical antipsychotic drug used to treat mental illnesses, such as bipolar disorder and schizophrenia. But patients who take Seroquel are 70% more likely to become diabetic than those who don’t take this drug, a risk that the drug manufacturer AstraZeneca was aware of as early as 2000. Joe Schneider and Margaret C. Fisk of Bloomberg.com report AstraZeneca’s release of its internal studies that suggested causal links between Seroquel and “diabetes and related conditions.”

Not only should patients watch out for the increased risk of diabetes that Seroquel and similar drugs (they are in a class called “atypical antipsychotics,” including Abilify, Zyprexa, and others), they need to be aware of the mental illnesses that these drugs are approved to treat. A Reuters article reports that an AstraZeneca sales representative marketed Seroquel as a depression-treating drug to a physician, which is an unapproved use of the drug. Although it is not clear from the article what dangers are associated with treating depression with Seroquel, it is safest to limit use of these powerful drugs to what they're approved to treat.

Nearly every week, we hear more evidence that American children are over-medicated, especially with drugs that affect mood and behavior. Most recently, a panel of experts has denounced the overuse of Risperdal, a powerful antipsychotic drug, for attention deficit disorder. The drug has too many side effects, including potential development of permanent muscle twitching, to justify its use in mild conditions like ADD for which other options exist, according to the expert panel convened by the Food & Drug Administration to advise it on labeling changes.

What is behind the explosion in use of antipsychotic drugs in children (besides Risperdal, they include Zyprexa, Seroquel, Abilify and Geodon) is a drumbeat of support from leaders in child psychiatry. But that leadership is tainted by their ties to the drug industry -- ties that frequently don't get mentioned in public when these same doctors are lecturing their colleagues and advising worried parents. One leader, Dr. Joseph Biederman, a child psychiatrist at Harvard, was revealed by a Congressional investigation to have accepted $1.4 million from manufacturers of antipsychotic drugs that he did not disclose to his university. Another psychiatrist leader, Dr. Charles B. Nemeroff of Emory, had to step down as chair of psychiatry after it was revealed that much of his consulting pay from drug makers, which totaled over $2.8 million in seven years, had been hidden from his university.

Now another influential psychiatrist has been exposed for his secret ties to the drug industry. He is Dr. Frederick Goodwin, former chief of the National Institute of Mental Health, who hosted a popular show on National Public Radio, "The Infinite Mind." Senator Charles Grassley of Iowa released data to the New York Times showing that Dr. Goodwin received $1.3 million from drug manufacturers from 2000 to 2007 for giving marketing lectures to other doctors. The money was never mentioned on his radio show, and NPR now says the show has been canceled and all reruns will stop soon.

According to the Times' Gardiner Harris, on one day in 2005, Dr. Goodwin received $2,500 from GlaxoSmithKline to give a talk about its mood stabilizer drug Lamictal at a Ritz Carlton resort in Florida. On his radio show broadcast the same day, Dr. Goodwin said that children with bipolar disorder who did not get treatment could suffer brain damage (a controversial prognosis) but he reassured his listeners that mood stabilizer drugs were a safe and effective way to treat the problem.

Senator Grassley has sponsored legislation to require drug makers to post publicly all the payments they make to doctor consultants. That would help the public to know whether the recommendations they see from doctors for medicating their children are truly unbiased or should be taken with a grain of salt.

Millions of people with normal cholesterol levels in their blood could be started on cholesterol-lowering statin drugs based on a new research study, but if patients understood the numbers behind the study, they might not move so fast to put statins in their medicine cabinet. Every patient can benefit from a closer understanding of how statistics work in medicine to push people toward treatments that they may or may not really benefit from.

The latest study involves people who were put on cholesterol-lowering statins because they had a high result on a blood test called C-Reactive Protein, even though the same people did not have high cholesterol.

As reported by Tara Parker-Pope in the New York Times' "Well" blog, here are the key numbers:

* The researchers reported an impressive sounding 50 percent reduction in heart attacks in the group treated with statins, as compared to patients in the same study who got a sugar pill (placebo) instead.

* But the real numbers of actual patients helped by the statins were only around nine in every 1,000 people treated -- less than one percent.

How do those numbers fit together? In the placebo group, 18 of every 1,000 patients suffered a heart attack or some other serious heart event during the study. In the group taking the statin drug, nine of every 1,000 patients had a serious heart event. That's how the researchers could report that the risk had been cut in half -- from eighteen to nine -- although the actual numbers of patients were few. Comparing eighteen to nine is called a relative risk ratio. Comparing 18/1,000 to 9/1,000 is called comparing the absolute risk. The absolute risk number is usually more meaningful.

Another important number for patients to understand in figuring out if a new medicine is for them is called the "number needed to treat." How many patients need to be treated with the new drug for one patient to benefit?

According to a New England Journal of Medicine editorial which analyzed the new study, 120 patients would need to be treated with statins over two years for just one of those patients to benefit.

That number might be enough to persuade some patients to take the drug. But it's a lot different than fifty percent. Bottom line: to make intelligent choices about treatments, patients need to understand how many patients like them are really expected to benefit from the treatment.

The Institute for Safe Medication Practices, a watchdog group, points out that the number of deaths (4,825) and injuries (21,000) from prescription drugs have reached record levels in the first quarter of this year, representing nearly triple the number of deaths in the last quarter.

The blood thinner heparin and the anti-smoking drug varenicline are the most dangerous, according to the statistics.

And where do these statistics come from? That is the worrying part, because they are probably underestimating the reality of the situation:

The data came from voluntary reports of adverse effects to the Food and Drug Administration, which made the data public after stripping information that identified victims. Because the reporting is voluntary, researchers have speculated that fewer than 10% of adverse events actually makes it into the system.

However, the article points out that since the dangers associated with heparin have been recognized, deaths and injuries have gone down. Varenicline is a different story:

Varenicline remains an ongoing problem, however, according to institute officials. Since the drug -- sold in the United States by Pfizer Inc. under the brand name Chantix -- was approved in 2006, it has been linked to 3,325 serious injuries and 112 deaths.

Some reports were linked to people attempting suicide or causing injury to themselves after using the drug, which can evoke serious psychiatric problems. Others were linked to blackouts, seizures or loss of consciousness, perhaps tied to sudden disturbances in heart rhythm...

...One possible explanation for the link might have been the success of the drug and the large number of people using it, the report said. But investigation showed that, during the quarter, varenicline accounted for more reports of serious injury than the top 10 best-selling prescription drugs combined.

We have all looked at the newspaper and noted with interest that some new drug cures 75% of the people who take it.

Some of us may have even based our medical decisions around information acquired in this way, maybe by going to the doctor and asking for that particular drug.

Unfortunately, the study that said the drug was very effective might have been funded by the same people who made the drug--and the article might not have told you that.

From the article:

The mainstream media often fail to report when drug company funding is used for studies of medications, a new review found.

What's more, there's a tendency among both medical and mainstream reporters to use brand names, rather than generic names, when referring to specific medications.

And both of these factors work to skew public and medical opinion toward commercial interests, according to the review, published in the Oct. 1 issue of the Journal of the American Medical Association.

This, despite newspaper editors' assertions to the contrary, the study authors found.

The lead author of the study, Dr. Michael Hochman, argues that everyone should try to refer to drugs by their generic names rather than by their brand names--in order to separate specific drug companies from the discussion of what drug is best for a patient.

Everyone who gets information about drugs from the media should keep this in mind as we read.

It's also a good idea to follow the seven-year rule -- do not take a drug within its first seven years on the market. That is because the injuries and dangers from the drug often don't become well known until it's been on the market for some time. See Public Citizen's Health Research Group web site for a good discussion of practical advice for patients in reducing their risks of harm from drugs.

Forbes Magazine has an informative article on the frequency of hospitals making mistakes while caring for patients, pointing out that 1.5 million Americans fall victim to such errors every single year.

Some of these errors occur through sheer carelessness: for example, 100,000 people a year die from "superbugs," bacteria that are resistant to available antibiotics. Infections from these superbugs can frequently be prevented by hand-washing. Yet other errors are the system's fault and not the fault of any individual. They occur because of overcrowding and the consequent inability of doctors and nurses to spend sufficient time with each patient.

The article also cites an Auburn University study showing that hospitals administer the wrong drug one time out of five. The dosage of the drug is another common source of error. A famous recent example of a drug error is from last November when actor Dennis Quaid's newborn twins were given 1,000 times the intended dose of the blood-thinner heparin. Luckily the hospital detected the error before permanent damage was done.

What is the bottom line? There are no magical solutions, especially since most of these problems are systemic. As a doctor quoted in the article says: "If you're sick, the best way to avoid getting sicker is to take charge of your care." Asking questions and being unafraid to make demands is the most any individual patient, or their loved ones, can do to reduce risk of error.

Tara Parker-Pope recently had an article on how fewer and fewer patients trust their doctors.

About one in four patients feel that their physicians sometimes expose them to unnecessary risk, according to data from a Johns Hopkins study published this year in the journal Medicine. And two recent studies show that whether patients trust a doctor strongly influences whether they take their medication.

The distrust and animosity between doctors and patients has shown up in a variety of places. In bookstores, there is now a genre of “what your doctor won’t tell you” books promising previously withheld information on everything from weight loss to heart disease.

What are the reasons for this new distrust? Several factors appear to be involved:

(1) Patients often don't understand what is going on with their health care because doctors and nurses are too rushed to explain things to them. Dr. Sandeep Jauhar, cardiologist and author of Intern: A Doctor's Initiation, is quoted in the article with a story of a patient who was transferred from one hospital to another with no explanation for why. He blamed a "broken system" for such failures to communicate.

(2) There has been greater coverage in the news of medical error, the power of the drug industry and the flaws in health care administration.

(3) The Internet makes information much more available, so patients can be informed skeptics. Drug companies also market directly to patients, so they come into the doctor's office with their own desires and opinions on what medications they should take. The upside to this is that patients have the information to challenge a doctor's errors. The downside is that many end up taking a drug commercial, for instance, at face value and will not listen to a doctor's reservations about the efficacy of a drug.

Again, from the article:

“Doctors used to be the only source for information on medical problems and what to do, but now our knowledge is demystified,” said Dr. Robert Lamberts, an internal medicine physician and medical blogger in Augusta, Ga. “When patients come in with preconceived ideas about what we should do, they do get perturbed at us for not listening. I do my best to explain why I do what I do, but some people are not satisfied until we do what they want.”

The whole article is worth reading. In addition, the article's page also has an embedded video clip of interviews with people discussing their attitudes to their doctors.

Laura Landro, in her column "The Informed Patient," discusses the problem of adults neglecting to get vaccinated for new illnesses. Not only that, but adults forget or are unaware that some childhood vaccinations lose efficacy after some time and need to be re-done. Skipping pre-travel vaccinations is also a common error.

Part of the problem is insurance: not only is vaccination for the very young more likely to be encouraged, but it is also more likely to be covered by insurance providers.

The whole column is worth a read, but here are some disturbing statistics Landro cites:

-only 2.1% of adults are vaccinated for tetanus, diphtheria and whooping cough, despite the existence of a combination vaccine for all three.

-only 1.9% of adults have been vaccinated for shingles. The shingles vaccine is recommended for all adults over 60.

-only 10% of women from 18 to 26 have received the vaccine for human papillomavirus, which can lead to cervical cancer, and which most insurance providers will cover.

Previously, this blog has discussed the contaminated heparin (a blood-thinning medication) found in the U.S. and linked to deaths and injuries.

Now the Food and Drug Administration has received reports of deaths tied to medical devices that use heparin, although they are not currently sure whether the heparin in these devices is contaminated.

From the article:

The FDA said the majority of the adverse events, which occurred from Jan. 1 to May 14, were associated with the use of heparin-lock flush solutions but also include heparin-coated oxygenators and circuits used during cardiopulmonary bypass procedures.

After his newborn twins were given near-fatal doses of the blood-thinner heparin, actor Dennis Quaid testified in front of Congress defending consumers' rights to file suit against pharmaceutical companies.

From the article:

Beginning with the Bush administration, the Food and Drug Administration has stepped into suits on the side of defendant pharmaceutical companies, arguing that federal regulation of drugs pre-empts state suits.

The article also reminds us that thousands of people die each year from medical errors. Lawsuits like the one Quaid is filing against Baxter Healthcare Inc. (the maker of the heparin) are one way of holding those who make these errors accountable.

Tara Parker-Pope of the NY Times has an article on how more than half of the writers of the DSM-IV--the Diagnostic and Statisical Manual of Mental Disorders--have financial links to the drug industry.

The DSM is the most commonly used handbook of psychiatric disorders. Clearly these financial links suggest a conflict of interest.

From the article:

It’s not the first time the D.S.M. has been linked to the drug industry. Tufts University researchers in 2006 reported that 95 — or 56 percent — of 170 experts who worked on the 1994 edition of the manual had at least one monetary relationship with a drug maker in the years from 1989 to 2004. The percentage was higher — 100 percent in some cases — for experts who worked on sections of the manual devoted to severe mental illnesses, like schizophrenia, the study found.

Oral contraceptives significantly reduce risks of ovarian cancer in women, says a new large-scale study. The pill has been linked to reduction in breast cancer rates as well, but not so large as the reduction in ovarian cancer rates.

The risk reduction persists up to thirty years after a woman stops taking the pill, although it declines with time. The risk reduction is also stronger in women who take it for long periods of time.

Furthermore, as the linked article says:

The proportional risk reduction for every 5 years of use was 29 per cent up to 10 years of stopping use, 19 per cent for 10 - 19 years after stopping, and 15 per cent for 20 - 29 years after stopping.

Out of nineteen industrialized nations, the U.S. has the most deaths that could have been prevented by access to timely, effective medical care.

Ellen Nolte and Martin McKee of the London School of Hygiene and Tropical Medicine performed the study, looking at deaths before the age of seventy-five caused by numerous diseases and complications. They found that France performed the best by this measure--though France, and other countries that ranked higher than the U.S., spends less money on health care than the U.S. does.

Not only was the U.S. the worst in these rankings, but we Americans are also ranked four places lower than we were in the last study (which covered 1997 and 1998). We are getting worse and spending more money.

Anti-psychotic drugs such as Haldol and Risperdal were developed to treat schizophrenia, but have recently been used for much broader purposes. They have been used to treat aggression in people suffering from everything from attention-deficit disorder to depression to the intellectually handicapped.

A new study finds, however, that these drugs are no more effective than placebos in treating aggression in the mentally disabled. This suggests that the drugs are being abused, and should be prescribed less often.

A thirty-year analysis shows that anemia drugs produced by Amgen Inc. and Johnson & Johnson raise the risk of leukemia incidence.

The following drugs are implicated in this study: Aranesp and Epogen (by Amgen Inc.), and Procrit (by Johnson & Johnson).

In addition, the steroid danazol was linked to higher risk of leukemia.

Shockingly, nursing homes having been giving elderly residents anti-psychotic drugs--not to combat actual psychosis, but rather to quiet symptoms of Alzheimer's or other forms of dementia and make the patients more docile and controllable.

This overuse of anti-psychotics is so rampant that it accounts for why Medicaid has recently spent more money on anti-psychotics than on any other type of pharmaceuticals.

This is not wholly due to malicious intent on the part of the nursing homes, but also on the fact that federal insurance programs are more willing to give money for drugs rather than for the extra staff that are needed to care for elderly patients with dementia.

This report highlights how medical institutions can harm the most vulnerable patients by giving them medications they do not require in order to meet economic or administrative goals.

Acute sinusitis is often treated with antibiotics, and possibly also a topical steroid.

However, a recent study found this common treatment to be no more effective than a placebo.

Commenters on the study have noted that there may be some patients for whom antibiotics might help, but there is no reliable way for a clinician to tell those patients from the others.

It is possible that this result is due to the greater level of resistance to antibiotics that has resulted from increased use of antibiotics over the last few years.