The FDA's poor oversight of postmarketing studies

Abstract

The US Food and Drug Administration (FDA) prefers to approve drugs with a proven, clinically relevant endpoint (eg, prevention of stroke), but also considers surrogate endpoints (eg, reduction in blood pressure). This approach can be a double-edged sword. Although it might accelerate the approval of new treatment options for life-threatening illnesses, because of the uncertainty around clinical benefits, drugs could turn out to be ineffective or harmful to patients. Follow-up is crucial to ascertain whether a drug is actually clinically beneficial. But, according to a new report by the Government Accountability Office (GAO), the FDA is failing to properly oversee postmarketing studies of drugs approved on the basis of surrogate endpoints.The report found that between 1992 and November, 2008, the FDA approved 90 applications for drugs based on surrogate endpoints through its accelerated approval process but only two-thirds of postmarketing studies had been closed (ie, the required and requested studies had been completed or were no longer deemed feasible or necessary). The report also found that from January, 1998, to June, 2008, the FDA approved 69 applications on the basis of surrogate endpoints for new molecular entities through its traditional approval process. The FDA does not require drug companies to complete postmarketing studies to confirm the benefit of these drugs. But the agency had requested that drug sponsors complete 175 postmarketing studies to obtain other information. The GAO report showed that as of Feb 13, 2009, only half of these studies had been classified as closed. Furthermore, the report found that the FDA has never exercised its authority to withdraw a drug it approved based on surrogate endpoints under the accelerated approval process, even when postmarketing studies have been outstanding for nearly 13 years.The FDA's new commissioner, Margaret Hamburg, outlined her commitment “to prevent harm to the American people” through swift, aggressive, and effective enforcement of FDA laws and regulations. Ensuring that the agency acts quickly and boldly on incomplete postmarketing studies should be a priority in any such plans to reinforce FDA rules. The US Food and Drug Administration (FDA) prefers to approve drugs with a proven, clinically relevant endpoint (eg, prevention of stroke), but also considers surrogate endpoints (eg, reduction in blood pressure). This approach can be a double-edged sword. Although it might accelerate the approval of new treatment options for life-threatening illnesses, because of the uncertainty around clinical benefits, drugs could turn out to be ineffective or harmful to patients. Follow-up is crucial to ascertain whether a drug is actually clinically beneficial. But, according to a new report by the Government Accountability Office (GAO), the FDA is failing to properly oversee postmarketing studies of drugs approved on the basis of surrogate endpoints. The report found that between 1992 and November, 2008, the FDA approved 90 applications for drugs based on surrogate endpoints through its accelerated approval process but only two-thirds of postmarketing studies had been closed (ie, the required and requested studies had been completed or were no longer deemed feasible or necessary). The report also found that from January, 1998, to June, 2008, the FDA approved 69 applications on the basis of surrogate endpoints for new molecular entities through its traditional approval process. The FDA does not require drug companies to complete postmarketing studies to confirm the benefit of these drugs. But the agency had requested that drug sponsors complete 175 postmarketing studies to obtain other information. The GAO report showed that as of Feb 13, 2009, only half of these studies had been classified as closed. Furthermore, the report found that the FDA has never exercised its authority to withdraw a drug it approved based on surrogate endpoints under the accelerated approval process, even when postmarketing studies have been outstanding for nearly 13 years. The FDA's new commissioner, Margaret Hamburg, outlined her commitment “to prevent harm to the American people” through swift, aggressive, and effective enforcement of FDA laws and regulations. Ensuring that the agency acts quickly and boldly on incomplete postmarketing studies should be a priority in any such plans to reinforce FDA rules.