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Previous Volume 358:1354-1361 March 27, 2008 Number 13 Next

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ABSTRACT

Background The Prescription Drug User Fee Act (PDUFA) imposes deadlines for the completion of drug reviews by the Food and Drug Administration (FDA). Critics have suggested that these deadlines may result in rushed approvals and the emergence of unanticipated safety problems once a product is in clinical use.

Methods We assessed the association between the PDUFA deadlines and the timing of FDA drug approval by constructing dynamic Cox proportional-hazards models of review times for all new molecular entities approved between 1950 and 2005. To determine whether the deadlines were associated with postmarketing safety problems, we focused on drugs submitted since January 1993, when the deadlines were first imposed. We used exact logistic regression to determine whether drugs approved immediately before the deadlines were associated with a higher rate of postmarketing safety problems (e.g., withdrawals and black-box warnings) than drugs approved at other times.

Results Initiation of the PDUFA requirements concentrated the number of approval decisions made in the weeks immediately preceding the deadlines. As compared with drugs approved at other times, drugs approved in the 2 months before their PDUFA deadlines were more likely to be withdrawn for safety reasons (odds ratio, 5.5; 95% confidence interval [CI], 1.3 to 27.8), more likely to carry a subsequent black-box warning (odds ratio, 4.4; 95% CI, 1.2 to 20.5), and more likely to have one or more dosage forms voluntarily discontinued by the manufacturer (odds ratio, 3.3; 95% CI, 1.5 to 7.5).

Conclusions PDUFA deadlines have appreciably changed the approval decisions of the FDA. Once medications are in clinical use, the discovery of safety problems is more likely for drugs approved immediately before a deadline than for those approved at other times.

Source Information

From the Department of Government, Faculty of Arts and Sciences, Harvard University, Cambridge, MA (D.C.); and Harvard Medical School (E.J.Z., J.A.); and the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital (J.A.) — both in Boston.

Address reprint requests to Dr. Carpenter at Harvard University, Department of Government, N405, 1737 Cambridge St., Cambridge, MA 02138, or at dcarpenter{at}gov.harvard.edu.

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