Black Triangle

A must-read commentary on the Coxib story, due to be in JAMA later this month:

In recent weeks there has been considerable speculation on how the FDA authority and configuration can be bolstered to preempt a coxib-like problem in the future. There is ample evidence of the overemphasis and resource allocation for initial drug approval, with little priority for postmarketing surveillance. An independent drug safety agency or center that compartmentalizes the vital functions of approval and surveillance seems to be gathering broad support. Importantly, providing more authority to the FDA to shape and require the execution of vital trials is perhaps the most important lesson from the coxibs. Currently, for the FDA to mandate that a trial be performed in the postapproval phase of a drug, it has to confront the manufacturer that the drug in question may be withdrawn from the market. There is hardly a precedent for such a drastic step in the history of the FDA. Unfortunately, manufacturers of coxibs were not willing to initiate dedicated cardiovascular trials on their own accord. With early results of coxibs that brought out their prothrombotic potential, rapid initiation of follow-up randomized clinical trials was absolutely necessary. Furthermore, nearly half of “real world” patients with arthritis have coexisting cardiovascular disease, and essentially no trials addressed this vacuum of knowledge. Accordingly, legislation is needed to empower the FDA to require industry to conduct trials that are deemed necessary to ensure the safety profile of a drug. Had coxib trials been conducted 5 years ago in patients with established cardiovascular disease, when the benefit and risk were indeterminate, clinicians would have quickly learned the risk and potentially avoided a major cardiovascular calamity.

The combination of mass promotion of a medicine with an unknown and suspect safety profile cannot be tolerated in the future.