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FDA Tries to Silence Info Documenting Avandia Deaths

In a reflection of the FDA's enthrallment to Big Pharma, the loss of tens of thousands of lives from Vioxx is being dwarfed.

by Heidi Stevenson

6 July 2010

The FDA appears to have tried to prevent publication of information documenting a significant increase in deaths and cardiovascular disease from Avandia over its competitor, Actos. An FDA employee, Dr. David Graham, claims that an underhanded trick was used in an attempt to keep his paper, which documents significantly increased Avandia risks, from being published.

Dr. Graham is no stranger to attempted suppression of his work by the FDA, which also attempted to suppress his research documenting the dangers of Vioxx, a drug that killed at least 60,000 people, in 2004.

Apparent Sabotage of Publication of Graham's Avandia Research

A month ago, Dr. Graham claimed that the FDA was trying to prevent or delay publication of the manuscript by the Journal of the American Medical Association (JAMA). Shortly after he went public with his suspicion, the approval needed for publication was given. Note: This is the same thing that the FDA attempted to do against his Vioxx research.

The approval was granted only a short time after Dr. Graham went over the heads of the officials whose approval was required. In desperation, he sent an e-mail to Margaret Hamburg, FDA Commissioner, and Dr. Joshua M. Sharfstein, FDA Principal Deputy Commissioner, to get the study published in time for the anticipated FDA review of Avandia.

Dr. Graham had attached the manuscript of the paper to that e-mail. The manuscript was then leaked to pharmaceutical journalist, Ed Silverman, who promptly published it.

At first glance, that wouldn't seem like such a big deal. After all, it means that the information unearthed by Dr. Graham is available to the public. However, in the medical publishing world, it's a critical issue. Major journals like JAMA have a policy to publish only work that has not appeared elsewhere. The premature release of Graham's work, especially under the circumstances, threatened the official acceptance and recognition of his findings.

On learning of the leak, Graham contacted JAMA and stated that he believed the premature publication had been an act of sabotage. Apparently, the JAMA editors agreed. Graham stated,

In my view, and in the view of JAMA for sure, this was an attempt by people at the FDA to block the publication. The idea was that JAMA would invoke the Ingelfinger* rule, and the paper wouldn't get published, and it wouldn't have credibility.⁽¹⁾

*The Ingelfinger rule is that manuscripts are accepted for publication only if they haven't already been published elsewhere.

Graham went on to say that the JAMA editors

were very reassuring and basically at the end of the day said that this is a poison pill and we aren't going to swallow it. We know it's an important study, and if this is the length the FDA is going to to stop it, it must even be more important than we recognized.

That's the point, isn't it? Why would someone high up in the FDA leak an early copy of a study, if not to derail its formal publication? The only reason doing that would make sense is if the document is strong enough to prevent them from taking a desired action. In this case, the desired action would be to allow the continued sale of Avandia.

Why Would the FDA Try to Suppress Publication of Research?

The question, of course, is why the FDA would act in such a manner. First, the FDA approved Avandia with inadequate documentation, and then compounded the damage by later re-approving the drug as safe.

Second, the FDA is under the spotlight for its behavior in drug approvals. Senators Max Baucus and Chuck Grassley have been on the scent, having recently completed a two-year inquiry into the FDA's management of Avandia. They have asked why a long-term study was allowed to continue, when the FDA itself estimates at least 83,000 excess heart attacks between 1999 and 2007. In fact, the FDA labeled the trial's treatment of patients as "unethical and exploitative".

Senator Grassley stated

There's a real problem when FDA's office that reviews drugs that are on the market is an unequal player in drug safety efforts. It doesn’t make any sense to have these experts, who study drugs after they have been on the market for several years, under the thumb of the officials who approved the drug in the first place and have a natural interest in defending that decision. The Avandia case may be the most alarming example of the problem with this set-up. Both the FDA and Congress need to take every step possible to establish independence for post-market surveillance.

Third, the question arises: Why does the FDA behave in this manner? The answer is, of course, obvious: Money. Big Pharma funnels money into the FDA, both in terms of fees paid—foolishly mandated by law—and by paying off employees, albeit indirectly. The most obvious example is the recently departed FDA Commissioner, who acted largely as a shill for Big Pharma, Julie Gerberding. She wasted no time in taking the position of President of Merck Vaccines, just a few days after the required one year waiting period.

Avandia's Dangers

No studies have shown that Avandia is superior to its competitor, Actos, in any way, and it seems that only those studies financed by the manufacturer, GlaxoSmithKline (GSK), show that it's not more dangerous.

Avandia, generically called rosiglitazone, carries much the same risk and benefit profile that its competitor Actos, generically called pioglitazone, does. The concern is that its benefits are no greater than those of Actos, while its risks are significantly greater.

Graham's study analyzed 227,571 Medicare patients who were treated with either Avandia or Actos over a three-year period, and then followed up for another three years. The study found a significant increase in stroke, heart failure, death, and a composite of AMI (acute myocardial infarction), stroke, heart failure, or death. The following table⁽¹⁾ shows the increased risks:

To put this into terms that can be comprehended clearly, Graham noted that,

If you treat 60 people with this drug for a year, one more will have a heart attack, death, stroke, or hospitalization event than they would if they had been treated with Actos. And that ends up being multiplied by hundreds of thousands of people taking the drug at any given time. You start talking about huge numbers.⁽¹⁾

In other words, hundreds of thousands of people taking Avandia will suffer severe cardiovascular harm, including death, as compared to those taking Actos. These are numbers that dwarf the carnage of Vioxx!

FDA's Re-Review

The FDA has scheduled a re-review of Avandia for 13-14 July. The agency's reputation is on the line, since questions have arisen over the original approval and subsequent reapproval. The data on the dangers of Avandia compared to Actos are clear, in spite of the FDA's apparent attempts to suppress them.

The TIDE Study

Avandia's pusher, GlaxoSmithKline (GSK), has instituted a major study, named Thiazolidinedione Intervention With Vitamin D Evaluation (TIDE), comparing Avandia and Actos, and with Vitamin D added to the therapy. Planned to last over six years, it was started in May of 2009.

Naturally, it has been questioned in light of the damaging information about Avandia. As noted, the FDA has come under scrutiny by a Senate investigation for questionable ethics in allowing the continuation of a study when it's clear that one of the drugs in question results in significantly more harm, including death, than the other.

Yet, the FDA has not seen fit to cancel the TIDE trial. Why? What possible benefit can there be for anyone other than GSK?

What's the FDA's Intent?

Frankly, trying to find a positive spin for the FDA's intentions is beyond me. The fact is that Dr. Graham's attempts to publish his data of damning evidence about killer drugs were thwarted—fortunately without success—by the agency. That speaks volumes. Combined with the FDA's unwillingness to stop a study that, in light of the evidence, is subjecting its subjects to pointless risks, it adds up to an utterly crass lack of concern for the public's welfare in favor of a corporation's profits.

There can be only one rational view of the FDA's role in the safeguarding of the public's health: It's a farce—an ugly, sociopathic reflection of a public agency's complete disregard of its remit to safeguard public health in favor of the pursuit of profit, both its own and that of the Big Pharma corporations to which it's been subverted.

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