DC Medical Malpractice & Patient Safety Blog

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.