Advisers to the US Food and Drug Administration (FDA) recommended today that the agency modify restrictions on the sale of Avandia, a diabetes drug that has been controversially linked to increased risks of heart attack and stroke.
Half of the panelists said that the restrictions should be changed, but opinions varied as to exactly how. Most said they felt the drug should be made more available, in light of a new evaluation of clinical data that supported the safety of the drug. Seven of the 26 advisors wanted restrictions removed altogether; only five felt the restrictions should remain as they are. The FDA does not have to follow the recommendations of its advisory committees, but often does.
Avandia (rosiglitazone) has been under fire since 2007, when Steven Nissen, a cardiologist at the Cleveland Clinic in Ohio, published a meta-analysis of clinical trial data showing that Avandia poses a heart risk. In 2010, after FDA analyses reached similar conclusions, the agency restricted sales of the drug. European regulators, meanwhile, pulled Avandia off the market altogether.
But the FDA also ordered an independent review of a pivotal clinical trial, called RECORD, which specifically assessed heart risks of the drug. Although the trial itself found no increased heart risk, a previous FDA analysis had uncovered disturbing omissions in the data that seemed biased in favor of the drug. The subject of the advisory committee meeting this week was this re-evaluation of RECORD, a review conducted by researchers at Duke University in Durham, North Carolina, and funded by GlaxoSmithKline (GSK), the makers of Avandia.
The meeting often felt like a rehash of enduring themes from the six-year Avandia saga. Once again, panelists struggled to reconcile conflicts between individual clinical trials and meta-analyses that lump many trials together. Once again, watchers caught a glimpse of conflicts within the FDA, where watchdogs that monitor the safety of a drug post-approval work in the same division as the staffers defending their decision to green-light the drug in the first place. And while Nissen himself was not allowed to present at this year’s meeting, he made sure his voice was heard in a Forbes column challenging the FDA for giving such weight to a GSK-funded reanalysis of RECORD.
Following the vote today, panelist Charles Stanley, a pediatric endocrinologist at the University of Pennsylvania in Philadelphia, said he felt that reanalysis showed the restrictions should be removed. But he said he struggled with whether to recommend that the drug be pulled from the market anyway. Only a few thousand patients still take the Avandia, he noted, and diabetics have many other treatment options to choose from. “This is a drug that has been severely tainted,” he said. “I’m not quite sure whether anybody has any great interest in seeing it continue.”