Haste to find disease remedies can lay waste to patient safety, history warns

drugsinhand-201x300Whoa, Nelly. For Americans stuffing their heads with vague data about potential drugs to treat Covid-19 — including chloroquine, hydroxychloroquine, azithromycin, remdesivir, ritonavir, lopinavair, Actemra, Oseltamivir, Ribavirin, Umifenovir, interferon, baricitinib, imatinib, dasatinib, nitazoxanide, camostat mesylate, tocilizumab, sarilumab, bevacizumab, fingolimod, and eculizumab — let’s get a little perspective, please.

Let’s put things simply, especially for most ordinary folks who have no desire to play at being pharmaceutical experts: As of this writing, as noted online in a meta-review by the respected Journal of the American Medical Association, this is the reality about drugs for the novel coronavirus:

 “No proven effective therapies for this virus currently exist.”

Careful medical scientists are conducting randomized clinical trials to determine if many known substances may be effective in treating Covid-19.

This work takes time. It needs to be done in time-tested, rigorous fashion, so patients know that powerful substances that they may take will, indeed, benefit them and deal in measurable ways with an illness. They need to know that drugs won’t, due to unintended consequences, make them worse or even kill them.

History shows that this has occurred when pellmell efforts to combat illnesses have gone awry, creating their own dire results. Medical scientists know the urgency in finding any way to ease the enormous suffering that the novel coronavirus causes. They also know that raising false hopes, putting out unhelpful nostrums, harming or killing patients, and arousing the suspicion that medical scientists are conducting unauthorized, unethical human experimentation may damage health care and society for generations.

The public already may be getting a taste of this as the fervent promotion of anti-malarial drugs by President Trump and others gets subjected to scientific scrutiny.

“A small study in Brazil was halted early for safety reasons after coronavirus patients taking a higher dose of chloroquine developed irregular heart rates that increased their risk of a potentially fatal heart arrhythmia,” the New York Times reported. The Los Angeles Times reported that “in research done in France, hydroxychloroquine reduced neither deaths nor admissions to intensive care units among patients who received it. In a study conducted in China and another in Brazil, the two drugs failed to help patients clear the coronavirus faster.”

The CIA and the FAA, meantime have offered their own cautions to intelligence personnel and airline pilots about the anti-malarial drugs’ high risks and low prospects for helping to battle Covid-19.

As the New York Times reported of Dr. Andre Kalil, 54, a principal investigator in the federal government’s clinical trial of drugs that may treat the coronavirus, he has “decades of experience grappling with questions about the use — and misuse — of experimental drugs, [and] has rarely been more frustrated.”

“He has seen what happens when desperation drives treatment decisions. ‘Many drugs we believed were fantastic ended up killing people.’ …. ‘It is so hard to keep explaining that. Dr. Kalil is haunted by memories of the Ebola outbreak that ravaged Africa from 2014 to 2016. Then, too, doctors said they could not wait for scientific evidence, and untested drugs were given to suffering Ebola patients by optimistic physicians with noble intentions. In the long run, none of the drugs was ever approved in the United States for treatment of the disease.”

Americans have a collective memory that can be terrifying in its brevity. They may be too inclined to forget the nightmare that led to the tough drug testing regimens that long have safeguarded patients and their loved ones. As the New York Times recounted:

“Thalidomide, a sedative sold by a German drug maker, was said to relieve everything from anxiety to morning sickness, but it led to perhaps the greatest pharmaceutical scandal of all time. About 10,000 babies, many in Germany, Britain and Australia, were born with severe defects in the 1950s and 1960s after their mothers took it. Some babies had no arms or legs. Others had no ears or malformed kidneys. The scandal briefly flared in the United States, where the drug was given to about 20,000 Americans in loosely run clinical trials sponsored by two American drug makers. The crisis led to passage of modern drug safety laws in the United States that required pharmaceutical companies to prove their medicines worked through rigorous clinical trials.”

As the newspaper also noted:

“Historians say the lesson of thalidomide is one that society is still learning the hard way. Hundreds of thousands of Americans have died in an opioid epidemic that has its roots in the Food and Drug Administration’s approval of the painkiller OxyContin and dishonest, aggressive marketing of the drug by its maker, Purdue Pharma. Today, as the coronavirus circles the globe — claiming thousands of lives — there is a renewed push to rush potential cures to market, even if it means bypassing the checks and balances that were thalidomide’s legacy.”

There’s another dark chapter in medical science, often ignored, and with great pertinence to hurried efforts to deal with the Covid-19 pandemic. It dates to researchers’ rush to respond to a global outbreak of the paralyzing illness polio, much controlled and near elimination now. But as a medical journal recalled:

“In April 1955, more than 200, 000 children in five Western and mid-Western USA states received a polio vaccine in which the process of inactivating the live virus proved to be defective. Within days there were reports of paralysis and within a month the first mass vaccination program against polio had to be abandoned. Subsequent investigations revealed that the vaccine, manufactured by the California-based family firm of Cutter Laboratories, had caused 40 000 cases of polio, leaving 200 children with varying degrees of paralysis and killing 10.”

Expectations may run high these days that researchers will make a coronavirus breakthrough in lightning strike-fashion — why not, especially with technology at medical scientists beck and call, and internet-assisted information sharing occurring as never before.

Alas, the traditional processes that rested on peer-review and proven ways of trying to eliminate doubt by thinking through experiments before conducting them, especially so their results could be repeated by others, may have been sundered by technology’s rise. Yes, researchers want to change and save lives by getting their earliest results out, as fast as possible. But the laurels — and financial support — too often goes to the early claimants, even if others may have more significant findings, later. So, in the time of the Covid-19 pandemic, with online preprints and other ways of disseminating studies online and through social media, researchers are putting out rougher drafts than they might ever have before.

Journalists and politicians, locked in 24/7 news cycles and confronting not only disease and death but also joblessness and economic calamity, have played their own unfortunate roles in seizing on wisps of medical science — in best intentions, perhaps, to foster hope, but also possibly with agendas that scholars and historians will best sort out, later. Anecdotes, and tales of singular experiences, can substitute for clinical findings that can be widely applied and relied on.

And for Big Pharma, of course, altruism may be a motivator but maximizing profits always seems to take precedence.

The global hunt for Covid-19 treatments is, in its own way, chaotic and lacking in leadership, critics say.

Just a gentle reminder that, over decades, researchers developed a multistage testing process to ensure the safety and effectiveness of drugs. In the first or preclinical phase, they might spend years in lab studies, for example, to determine the basic science needed to attack a condition. In the second phase, with tens of individuals’ help, they might test the safety for humans of study substances. This would be expanded to larger numbers, in the hundreds, to ensure patient safety. It is only in the last stage, which can involve thousands and can take years, that scientists study both the safety and effectiveness of a proposed remedy.

To be sure, research may be expedited with many of the therapies under consideration because they already have gone through these steps and won approval for patient care.

Still, researchers must proceed with caution, especially if they are combining drugs. They also need to set up studies, so they do not produce misleading results. Many of the trial subjects from the early part of the outbreak in China, involved patients already in bad shape. Which of many treatments that these desperate individuals received truly benefited them and to what degree? This can get complicated quickly.

Because of the circumstances under which Covid-19 researchers are studying treatments, they also must struggle to deal with ethical considerations and validation of their results with blinded and controlled trials. To avoid taint and false positives, especially from the placebo effect, can they withhold a drug from one group of ill patients, giving it to the other, so they have a control? Can this be randomized, so those administering the drug not only don’t know who is getting the real things and who is not but also so patients with certain characteristics don’t over-weight results? If these issues aren’t tough enough already, doctors also must wrestle with their measures of success: Will they advance therapies that help some patients breathe better but increase the risks of heart problems? Will they find a drug useful if it helps a few or must it be many patients? Will they find drugs that are helpful early in an infection but that may not work much later?

In my practice, I see not only the harms that patients suffer while seeking medical services, but also the damage that can be inflicted on them and their loved ones by dangerous drugs. There were clear, solid reasons — and they continue to exist — as to why this nation chose to rein in Big Pharma and safeguard patients with tough testing processes for potent prescription medications and therapies. These may have been over cautious, and adjustments were made after the HIV-AIDS crisis.

But drug and medical device makers, with a huge boost from business-friendly politicians, have assaulted federal regulation, clamoring with success for shorter, lighter, and less tough oversight. The results have proven problematic already, with expensive prescription drugs — notably to treat advanced cancers — getting to market, too often with improving on existing therapies. Instead, Big Pharma has argued for the meds’ approvals, say, because they may shrink a tumor for a time rather than demonstrating they improve or extend patients’ lives.

Will the understandable haste to deal with Covid-19 lay waste to the good science that has given Americans safe, reliable, and effective drugs? Will medical publishing be further degraded, not only by outright trolls, pay for play authors, conflicts of interest, shoddy work requiring retraction, but also minimally reviewed and quick dissemination?

We’ve got a lot of work ahead of us to not only find treatments that work to battle Covid-19 but also to ensure that the pandemic does not harmfully infect science and safeguards for the prescription drugs we need.

Patrick Malone & Associates, P.C. listed in Best Lawyers Rated by Super Lawyers Patrick A. Malone
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