After sitting through about 17 hours of talk over the last two days about GlaxoSmithKline’s much-maligned diabetes drug Avandia (rosiglitazone), it’s still near impossible to tell exactly where the truth lies.
If you are to believe Glaxo, the truth does not lie. Whereas David Graham, the FDA’s very own iconoclast, and Steven Nissen, the always-ready-with-a-quote Cleveland Clinic cardiologist, seemed to have had to sit on their hands to keep from bursting out, Joe Wilson-style, “you lie!”
The July 13-14 joint meeting of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee — a referendum on the drug’s safety — was a curious confluence of pro- and anti-Avandia forces, all of whom claimed to have science on their side (background materials posted here, on July 9).
I don’t usually like to bring myself into these posts, but I have been covering FDA advisory committee meetings for, oh, about 20 years, and I can probably count on one hand the number of times I’ve witnessed panel members, speakers, and FDA staff openly question the truthfulness of a manufacturer’s data submission.
No doubt that sloppy paperwork has always existed, but I don’t recall ever seeing it so vividly dissected and displayed in such a public forum. Thomas Marciniak, an FDA medical reviewer who got handed the Avandia file last fall for the first time, aired Glaxo’s dirty laundry multiple times over the course of the two days. The self-acknowledged bloodhound of an investigator said that in Glaxo’s pivotal safety trial, RECORD, he found multiple instances of heart attacks disappearing off case reports and unreported deaths, even though the study ostensibly was focused on documenting cardiovascular events and mortality (his slides are here).
Even his boss, Ellis Unger (deputy director of the FDA’s Office of Drug Evaluation I), told the panel, “the issue here really is truth.” And Dr. Unger was avowedly in favor of keeping Avandia on the market.
The credibility conundrum seeped into panelists’ discussions. Many expressed consternation over Dr. Marciniak’s findings, but in the end, 20 of the 33 panelists said that Avandia should remain available as an option for patients.
It’s uncertain when the FDA will make a decision based on these panelists’ advice — there is no statutory timeline for the re-review of an already-marketed drug. But the Monday-morning quarterbacking has begun in earnest.
The New York Times played up the lack of credibility angle and portrayed Avandia as doomed. The Wall Street Journal said that analysts were factoring a big decline in sales into their overall estimates for Glaxo.
Meanwhile, the Union for Concerned Scientists called the meetings a “fiasco” in a press release. Public Citizen’s Health Research Group director Dr. Sidney Wolfe called on the FDA to immediately remove Avandia from the market. Mr. Wolfe spoke out against Avandia at the hearing (testimony here).
Meanwhile, the Endocrine Society, American Diabetes Association, and American Association of Clinical Endocrinologists put out a joint statement urging patients to talk with their physicians before giving up on Avandia.
So who to believe? Is Avandia safe? Is it dangerous?
The truth is, science is imperfect.
— Alicia Ault (on Twitter @aliciaault)