In recent years the FDA has come under increasing fire for approving drugs on the basis of surrogate endpoints without any evidence of greater clinical benefit. The most famous example of this is the diabetes drug rosiglitazone. Despite strong evidence demonstrating that it was effective at lower blood glucose levels– the surrogate endpoint– serious questions emerged about the cardiovascular safety of the drug, eventually leading to its near withdrawal from the market in the US (and full withdrawal in Europe). Questions have also been raised about the long term health effects of drugs targeting a specific endpoint– including cholesterol and other lipids, blood glucose, weight loss, and blood pressure.
Despite what some believe is a long-term trend against the use of surrogate endpoints, the FDA is actually seeking to make it easier for manufacturers of one therapeutic category, antihypertensives, to claim cardiovascular benefit for their drugs despite the absence of evidence to support most of these drugs.
Although the actual changes proposed by the FDA are small, I thought the issue bore further exploration. I first spoke with Norman Stockbridge, the director of the Division of Cardiovascular and Renal Products (DCaRP) in the Office of Drug Evaluation 1 at the FDA. I then asked Harlan Krumholz, Sanjay Kaul, and Franz Messerli and Sripal Bangalore to comment on this topic.