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Saturday, June 08, 2013

Avandia and the RECORD Trial Saga

Behind every great fortune lies a great crime. - Honore de Balzac

We are coming up on the one year anniversary of GlaxoSmithKline agreeing to pay a $3,000,000,000 fine for promoting its best-selling antidepressants for unapproved uses and failing to report safety data about a top selling diabetes drug. One of the antidepressants, Paxil, was the subject of Alison Bass's "Side Effect", A Prosecutor, A Whistleblower, and A Best Selling Antidepressant on Trial. Avandia, once the best selling oral diabetes drug in the world, was another piece of the GSK crime that built a great fortune. GSK hid safety data that pointed out serious cardiovascular risks. Nearly one year after GSK confessed their sins and agreed to pay the U.S. $3,000,000,000, an FDA advisory board has convened to reconsider their 2010 conclusions on Avandia.

Why? Steven Nissen has some interesting thoughts on the subject. 

In 2005 and 2006, GSK secretly conducted an analysis of the cardiovascular safety of Avandia and concluded that the drug increased the risk of heart attacks and related events by about 30%. This observation had grave implications: two thirds of diabetics, the intended recipients of the drug, eventually die of cardiovascular complications.
Cardiovascular side effects for pills given to a patient population where two thirds die of cardiovascular complications? Hiding something like this is one hell of a crime. It is ironic then that Paxil and Avandia made up only one third of the $3,000,000,000 fine. $2,000,000,000 in fines stemmed from a civil settlement over the sales and marketing practices from the asthma drug Advair and other drugs. What kind of an evil organization are we dealing with here?

The FDA and the CDER were created to deal with such problematic organizations and the harm they will inflict on us if we don't regulate. Unfortunately, in this case, it appears as though they decided to think of their own careers first. As Dr. Nissen points out:

In the middle of the sequester, CDER is willing to spend a large sum of taxpayer dollars to conduct a 2-day advisory meeting on a drug nobody uses, for the sole purpose of absolving its own bureaucracy of responsibility for a terrible drug safety tragedy. 

We have anti-depressant pills that come with a side effect of increased risk of suicide. We have diabetes drugs that put an already susceptible population at greater risk for having a heart attack. These are products from people who are suppose to be helping us. They have to gain approval through the agency that we put in place to prevent them from harming us. How does any of this happen?

In their response to the article written by Dr. Nissen, the FDA only explained why they did not invite him to speak. They failed to address the hard questions stating only:

FDA staff reviewed Dr. Nissen’s proposed topics and concluded they did not warrant a slot as an FDA guest speaker. The content of his proposed topics is expected to be covered by other speakers as agency staff plan to summarize the available data on the cardiovascular safety of rosiglitazone at the committee meeting, and multiple FDA speakers will address their review of the readjudication of RECORD trial based on the study reports submitted to the Agency.

But why are you revisiting the RECORD trial? As usual, the people with the power determine what subjects will be discussed. They determined that the RECORD trial needed another review without explaining what was wrong with the first one. It reminds one of the Baltimore Case. Keep holding government hearing with expert witnesses until you get the results you desire. Janet Woodcock explains here that:

Given the public interest in Avandia, the extensive history of the product, and the continued uncertainty of the risk surrounding this drug, FDA is holding this meeting to have a transparent, public discussion with experts across multiple scientific disciplines on the results of the readjudication of the study.

How much interest does the public have in a drug that no one uses? When did the risk uncertainty "continue" at the FDA? In 2010 the risk was certain. That is why the drug was pulled from the market. When did it fire back up?

To the lowly Cargo Cult Scientist, me, the RECORD trial saga demonstrates the anti-scientific method of drug approval and the role power plays in the approval process. Was there extraordinary bias in the conduct of the trial? Did GSK really change or delete data on unfavorable clinical events, sometimes months after they should have been reported? Will the FDA ever have to answer for the way in which they handled this trial in light of so many serious questions? It was a trial that exposed, more the most other trials, how flawed the system is and how far the FDA will go to absolve themselves of their mistakes. Just as Avandia poses a health threat to diabetes patients, the FDA poses a health threat to the general public.

We eagerly await the new and improved conclusions from the readjudication of the RECORD trial.

1 comment:

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