If, like a near-majority of your fellow Americans, you’re currently taking at least one prescription drug on a long-term basis, Vanity Fair‘s article on “Deadly Medicine” will make you feel a little sick(er):
Once upon a time, the drugs Americans took to treat chronic diseases, clear up infections, improve their state of mind, and enhance their sexual vitality were tested primarily either in the United States (the vast majority of cases) or in Europe. No longer. As recently as 1990, according to the inspector general of the Department of Health and Human Services, a mere 271 trials were being conducted in foreign countries of drugs intended for American use. By 2008, the number had risen to 6,485—an increase of more than 2,000 percent. A database being compiled by the National Institutes of Health has identified 58,788 such trials in 173 countries outside the United States since 2000. In 2008 alone, according to the inspector general’s report, 80 percent of the applications submitted to the F.D.A. for new drugs contained data from foreign clinical trials. Increasingly, companies are doing 100 percent of their testing offshore. The inspector general found that the 20 largest U.S.-based pharmaceutical companies now conducted “one-third of their clinical trials exclusively at foreign sites.” All of this is taking place when more drugs than ever—some 2,900 different drugs for some 4,600 different conditions—are undergoing clinical testing and vying to come to market.
Some medical researchers question whether the results of clinical trials conducted in certain other countries are relevant to Americans in the first place. They point out that people in impoverished parts of the world, for a variety of reasons, may metabolize drugs differently from the way Americans do. They note that the prevailing diseases in other countries, such as malaria and tuberculosis, can skew the outcome of clinical trials. But from the point of view of the drug companies, it’s easy to see why moving clinical trials overseas is so appealing. For one thing, it’s cheaper to run trials in places where the local population survives on only a few dollars a day. It’s also easier to recruit patients, who often believe they are being treated for a disease rather than, as may be the case, just getting a placebo as part of an experiment. And it’s easier to find what the industry calls “drug-naïve” patients: people who are not being treated for any disease and are not currently taking any drugs, and indeed may never have taken any—the sort of people who will almost certainly yield better test results. (For some subjects overseas, participation in a clinical trial may be their first significant exposure to a doctor.) Regulations in many foreign countries are also less stringent, if there are any regulations at all. The risk of litigation is negligible, in some places nonexistent. Ethical concerns are a figure of speech. Finally—a significant plus for the drug companies—the F.D.A. does so little monitoring that the companies can pretty much do and say what they want.
One big factor in the shift of clinical trials to foreign countries is a loophole in F.D.A. regulations: if studies in the United States suggest that a drug has no benefit, trials from abroad can often be used in their stead to secure F.D.A. approval. There’s even a term for countries that have shown themselves to be especially amenable when drug companies need positive data fast: they’re called “rescue countries.” Rescue countries came to the aid of Ketek, the first of a new generation of widely heralded antibiotics to treat respiratory-tract infections. Ketek was developed in the 1990s by Aventis Pharmaceuticals, now Sanofi-Aventis. In 2004—on April Fools’ Day, as it happens—the F.D.A. certified Ketek as safe and effective. The F.D.A.’s decision was based heavily on the results of studies in Hungary, Morocco, Tunisia, and Turkey.
The approval came less than one month after a researcher in the United States was sentenced to 57 months in prison for falsifying her own Ketek data. Dr. Anne Kirkman-Campbell, of Gadsden, Alabama, seemingly never met a person she couldn’t sign up to participate in a drug trial. She enrolled more than 400 volunteers, about 1 percent of the town’s adult population, including her entire office staff. In return, she collected $400 a head from Sanofi-Aventis. It later came to light that the data from at least 91 percent of her patients was falsified…. Nonetheless, on the basis of overseas trials, Ketek won approval.
As the months ticked by, and the number of people taking the drug climbed steadily, the F.D.A. began to get reports of adverse reactions, including serious liver damage that sometimes led to death. The F.D.A.’s leadership remained steadfast in its support of the drug, but criticism by the agency’s own researchers eventually leaked out (a very rare occurrence in this close-knit, buttoned-up world)… [O]ne day before the start of a congressional hearing on the F.D.A.’s approval of the drug, the agency suddenly slapped a so-called black-box warning on the label of Ketek, restricting its use. (A black-box warning is the most serious step the F.D.A. can take short of removing a drug from the market.) By then the F.D.A. had received 93 reports of severe adverse reactions to Ketek, resulting in 12 deaths…
The world is flat!…. -lining…
Yuck. Surely McMegan will blame this on Obamacare(tm).
If the drugs don’t kill ya, Sarah Palin will finish the job
The second point is actually a huge deal here. Leading someone to think they are being treated for a disease when they’re just part of a clinical trial is illegal in most countries in the West. In the US, there are huge disclosure rules for clinical trials and/or experiments of any kind, and staying within those rules adds up the costs enormously. So it doesn’t shock me that the drug companies choose to go outside the boundaries of those rules. The thing that gets me is that the ethical standard is supposed to apply to the study itself. So regardless of the results if the study was performed in an unethical fashion it gets thrown out period. The FDA is either showing willful ignorance or there is blatant corruption happening somewhere there.
* The percentage of Americans who used at least one prescription drug in the past month increased from 44% in 1999-2000 to 48% in 2007-2008.
* The percentage of persons who used two or more prescription drugs increased from 25% in 1999-2000 to 31% in 2007-2008.
* The percentage of persons who used five or more prescription drugs increased from 6% in 1999-2000 to 11% in 2007-2008.
More statistics at:
If anyone here uses Tylenol, then you are just like those people who took a so-called safe drug and now have suffered terrible side effects like liver damage and complete liver failure – there is no way that drug would be approved today considering its extreme damage both from very small over dose (2x – 3x can cause severe liver damage to even death) to interactions with alcohol – the drug is estimated to cause 3,000 – 4000 people per year to lose their livers (I am sure alcohol and taking different products that all have the drug are the biggest causes.) Notice that children’s Tylenol was pulled from the market due to unknown dose levels (too high/low!) and contaminates (WTF?!) That so-called safe drug is the greatest danger that any over-the-counter med currently available. Hay, it makes J&J billions, so who cares if a few thousand people die every year from the drug.
John - A Motley Moose
I believe this is the most attractive element for the drug companies – “Ethical concerns are a figure of speech”
Another issue that didn’t seem to be discussed has to do with population ethnic differences, as well as the range of ages of the test population. I believe there have been, or are, discussions of the actual efficacy of some drug trials based upon the test populations in the United States having been, historically, primarily white males with a narrow socio-economic range and age profile. Questions of various drugs’ efficacy in treating females, blacks or Asians, children or the elderly must be considered.
Just wait til the Conservatives take over and start their trimming of the federal budget.
They will cut the FDA since it is no longer needed. They will allow the corporations to police themselves. Because big Pharma won’t sell any medications that would actually cause harm to us.
I can hear the Libertarians right now spouting the nonsense about how the private sector can do this job so much better at a much cheaper cost.
Besides, we don’t need anyone in the Government telling the companies what they can and can’t sell.
As we all know the Government can’t run anything effectively. Or so the lunatics tell us.
Big Pharma isn’t stupid. Less cost and easier to purchase the results that you want in other countries.
On a realated note, the link below is to a recent article in The Atlantic that goes into a lot of detail about the bogus nature and bias of much medical research and a doc who has made it his mission to try and help correct this problem:
Lies, Damned Lies, and Medical Science
I’m shocked—shocked—to hear The Constant Gardener wasn’t fiction!
Theoretically, there’s an easy fix for this. The FDA just has to enforce the laws currently on the books in line with Congressional intent. Alas, it is well short of having the resources it needs to do that.
When Republicans talk about starving the beast, it’s mostly about four agencies: FDA, SEC, EPA, and OSHA.
You are so right about those agencies being short of the resources to do an effective job putting any teeth in the regs that are on the books.
I’ve worked in the military, the pharmaceutical and environmental testing and academia on the research side of things. All of them willfully broke federal rules left and right that could have gotten them shut down and that were downright dangerous in many cases.
Then on the other hand, some of the rules–such as OSHA rules on handling of some chemicals–are simply asinine. Some of the most ridiculous regs are those in which the same substances are sold to the public in a basically unregulated manner and zero regulations are required regarding storage, handling or disposal.
I take a generic blood pressure medicine, enalipril. Prior to that it was “Vasotec” at a monthly cost of $93.00, when it went generic in the early 2000’s it dropped to the mid twenties, now its $11.00 a month. My Doc started writing 3 month scrips rather than monthly, guess what? Its still $11. but now its for 90 pills rather than 30! What does this shit cost to manufacture? Its still made by Merck in one of their generic plants. CVS started carrying another brand of generic enalipril, they gave me a supply (same price) I broke out in a rash within two days and suffered for over a week until my doc and I figured it out. Within 24 hours of switching back to my original generic, the rash was gone. I would have never (or my doc) put two and two together if the color wasn’t different. Turns out the new generic was made in China. I must have been reacting to the wallboard they use as filler!
There was a Leverage episode this season based on a similar story. In the episode post on KFM, several people said that the villain seemed a little over-the-top. John Rogers replied that they usually tone the villains down, because the real stories seem so implausible.
Two points in response:
Drugs typically cost next to nothing to manufacture; margins, even on generics, are astronomical. Big Pharma will tell you that they have to make that much money in order to fund research, and they’re not entirely wrong, but a lot of other countries around the world have used compulsory licensing and price controls to force American consumers to fund all of the world’s pharma research.
Bioequivalence is a crapshoot. Some generics really do work as well as the branded product, some don’t come close.
There are more and more areas where I used to assume (admit it, we all did) that somewhere behind the scenes the right rules were in place to prevent extremely stupid, awful things from happening. Which is scary considering how many aspects of our lives we basically take it on trust that someone out there is keeping things safe.
One by one, we’ve learned that, behind the scenes, things are even worse than we thought. Prescription drugs are one example. A few others: Food safety. Risk management at banks. Competence and decency in the military (remember “a few bad apples”?). How many other horrible cases are out there waiting to be discovered?
There are a number of valid concerns raised in the Vanity Fair article, but there are also a number of inaccuracies. Big ones.
For example, it is not correct to say that FDA does not inspect foreign manufacturing plants. I can tell you for a fact that they do, and that it is standard practice. But, they are also bound by resource and budget constraints, which means that they do not do frequent, routine monitoring of manufacturing facilities. This means that FDA might not have caught an issue like the Chinese contamination of herceptin before the contaminated drug went into distribution, unless it were routine and proceduralized.
The article seems to blame FDA for much of the problems that they cite, but it’s not as simple as that. First, the pharmaceutical industry is dominated by big corporations, whose main purpose is to make as much money as possible. As Michael Moore rightly pointed out, corporations are amoral. Right and wrong have very little meaning to corporations, and certainly take a backseat to maximizing profits.
As such, the pharmaceutical industry is constantly testing the limits of what it can get away with to maximize profits. This makes the role of FDA as a regulatory gatekeeper and enforcer that much more critical. But, the FDA is challenged by a lack of appropriate funding and resources overall, and by weaknesses in federal regulations. It also doesn’t help that the Bush Administration mismanaged the Agency for 8 years, while the pharmaceutical industry continued to entice experienced FDA officers to leave government service for higher paying jobs in the industry.
The article is also somewhat superficial in covering the complications inherent in clinical trials. In the Celebrex case, the adverse events were observed in clinical trials, but in small enough numbers that GSK was able to conceal them. Once the drug was approved and in the marketplace, the numbers of patients being treated was much larger, and the adverse events became much more obvious. In this case, GSK was certainly at fault. But this does underscore a basic problem in pharmaceutical development.
That is, virtually all drugs have side effects of one type or another. In some cases, those side effects can be very rare, only affecting small subsets of the population. If a rare side effect only affects 5-10 people in 100,000, that would still amount to a lot of people if the drug were administered widely in the US population. However, a big clinical trial might only involve 5000-10,000 patients. That means that some rare side effects might not be apparent after clinical trials, or might easily be overlooked or disregarded (intentionally or otherwise).
All this underscores the need for strong regulation and for a strong, adequately resourced FDA. Unfortunately, the American people just put the wrong party into the majority in the House for anything positive to come in that direction.