An advisory panel to the U.S. Food and Drug Administration (FDA) voted on Wednesday not only to let the controversial diabetes drug Avandia remain on the market but also to continue a large clinical trial comparing the safety of Avandia with another, similar drug, Actos.
The vote to continue the drug trial came even though a majority of the 33 panelists said they believe current findings are sufficient to raise “significant safety concerns” about Avandia’s potential to cause heart attacks and other cardiovascular problems in comparison to Actos. Indeed, 12 of the committee members voted to recommend banning Avandia, also known as rosiglitazone.
The divided vote only seems to reinforce the question some researchers have been asking for months about the so-called TIDE trial comparing Avandia and Actos.
In an interview two weeks before the advisory panel met, David Graham, an FDA drug safety expert, said it’s unethical to do a trial to see how much harm a drug does to people.
Patients chosen to take Avandia as part of the trial “are not going to get any unique benefit, but they are guaranteed to get extra harm,” said Graham, who has advocated for Avandia’s withdrawal.
“They are being basically tricked into participating in a study that is unethical,” he added.
David Juurlink, M.D., a clinician and University of Toronto drug-safety researcher, has also called on regulators to halt TIDE. “Here are two drugs with identical clinical indications, and there’s a fairly strong signal that one of them is less safe than the other,” Juurlink, said. “So if you’re a patient,” he added, “why would you want to go on that drug? Would you really want to be randomized in a study to a drug that might kill you? That has no benefit?”
On the other hand, the committee’s votes also make clear that many of its experts consider the data on Avandia’s cardiovascular risk to be inconclusive.
“Having reviewed the data in great detail, I’m not sure if this is an unsafe drug,” says David Nathan, M.D., a Harvard professor and director of the Diabetes Center at Massachusetts General Hospital. “If we’re ever going to answer the question—and if this drug is still on the market I think we have to answer it—then you have to do the study.”
Nathan, who is not on the FDA panel, says he does not prescribe Avandia but can imagine instances where it might be appropriate, say for a patient who has done extremely well on it and is at relatively low risk for cardiovascular complications.
No research has suggested that Avandia carries any particular advantage over Actos. Both drugs are most often used as add-ons to other diabetes drugs to reduce blood sugar.
The TIDE trial was launched last year by Avandia’s maker, GlaxoSmithKline, at the request of the FDA. With hundreds of trial sites around the world, it is set to enroll more than 15,000 patients, with a completion date of 2015.
Katharine Greider lives in New York and writes about health and science.