FDA Medical Reviewer Slams RECORD Trial Conclusions, Casting Further Doubt on Avandia

July 9, 2010, 9:00AM. By Gordon Gibb

Washington, DCThe US Food and Drug Administration (FDA) today stated through a posting on the official FDA website that GlaxoSmithKline (Glaxo), the manufacturer of Avandia, may have misinterpreted crucial details of a study that it said had vindicated Avandia and found the Type 2 diabetes drug to be safe.

A medical reviewer with the FDA said that, correctly interpreted, the study finds that Avandia could indeed cause heart attacks. According to this morning's issue of the New York Times, Dr. Thomas Marciniak noted in his post that Glaxo's misreading of the RECORD trial was so profound as to suggest "serious flaws with trial conduct."

To come to the conclusion that a combined look at all the trials of Avandia demonstrates that it causes heart attacks, he wrote, "one does not have to be a mathematician or to perform calculations."

The revelation could not come at a worse time for Glaxo as it prepares for a crucial test of its one-time blockbuster drug next week. A panel of experts will convene in days to advise the FDA on whether Avandia should remain on the market or be withdrawn.

That decision will ultimately fall to FDA Commissioner Dr. Margaret Hamburg, who is said to be more sympathetic towards public health than her predecessors.

There is much that will be discussed at the expert panel next week in Gaithersburg, Maryland. Some within the FDA say that observational studies are not sufficient to arrive at a definitive conclusion. Such proponents point to the controlled prospective study currently being conducted by Glaxo at the behest of the FDA as the only sure way to determine if Avandia is safe or dangerous.

However in a report released 7/9/10, according to the New York Times, the Institute of Medicine states that observational studies are, indeed, adequate. Some in the FDA are of the view that the current trial being conduct by Glaxo should be stopped since observational studies have already shown Avandia to be dangerous.

Still others question if the Glaxo study, which compares the safety and efficacy of Avandia with rival drug Actos, is even ethical.

Glaxo, in a statement, stood behind its drug. "Since 2007, we have seen results from six controlled clinical trials looking at the cardiovascular safety of Avandia, and together they show that this medicine does not increase the overall risk of heart attack, stroke, or death," said Dr. Murray Stewart, vice president for clinical development at GlaxoSmithKline.

However, Dr. Marciniak finds that the results of the RECORD trial, when interpreted more correctly, suggests substantial risks to the heart. According to the New York Times, critics of the RECORD study cited it for design flaws and durations too short to prove anything. A subsequent investigation by the senate Finance Committee suggested that Glaxo might have improperly influenced the independent experts in charge of the RECORD study.

The long-awaited expert panel on Avandia convenes next week.