Rosiglitazone Story a Reminder of Need for FDA Reform

August 8, 2007 (Boston, MA) - The man who chaired the recent FDA advisory panel hearing on rosiglitazone summarizes the sorry saga as follows: "A new 'wonder drug,' approved prematurely and for the wrong reasons by a weakened and underfunded government agency subjected to pressure from industry, had caused undue harm to patients."
That's the synopsis of Dr Clifford Rosen (St Joseph Hospital, Bangor, ME), whose Perspective in the New England Journal of Medicine this week argues that the FDA's advisory panel's struggle to resolve safety concerns about the drug should serve as a reminder for the ways in which the drug-approval process could be improved [1].
The panel's "dispassionate" efforts to make the right decision about rosiglitazone highlight three tenets that could be used for future drug approval, Rosen argues. First, the pathogenesis of disorders being targeted should be fully understood at the time of approval; second, treatment options must be evidence-based; and third, regulators should use a uniform approach to weigh the risks and benefits for society of any proposed intervention.
In the case of rosiglitazone, the drug was approved largely on the basis of a surrogate end point--glycemic control--yet change in glycated hemoglobin level has emerged as a "relatively poor surrogate for cardiovascular outcomes," Rosen notes.
"There is no doubt that it will be costly to undertake true safety and efficacy studies of new drugs using clinical outcomes as primary measures, but in the long run, these efforts will save time, energy, and money."
During the FDA hearing itself, several panel members conveyed an escalating disillusionment with the FDA's drug-approval process. Dr Arthur A Levin (Center for Medical Consumers, New York, NY) summed this up. "I, like everyone else, am frustrated by the lack of clarity and confidence in the data we have, which I think speaks to some real structural issues about how we approve drugs and how we monitor them in the postmarketing period," he said during the hearing. "Those of us who have sat through this frustrating experience before really need to push, because I've been in this situation too many times of being at a table where everybody is expressing frustration about having to make a difficult decision based either on data that are poor quality or inadequate quantity of evidence. We all should try to ensure that in future we're not in this same position again."
Echoing that sentiment, Rosen pointed to mounting calls for the FDA to fund and oversee phase 4 postmarketing studies that actually have some teeth. "One can only hope that the energy generated by the advisory committee meeting will be channeled into improving the open hearing process to better serve all interested parties," Rosen concluded.
Rosen C. The rosiglitazone story: Lessons from an FDA advisory committee meeting. N Engl J Med 2007; 357:1-3.