Bioethics Blogs

The Role Of Black Box Warnings In Safe Prescribing Practices

In the Health Affairs article, “Era of Faster Drug Approval Has Also Seen Increased Black-Box Warnings and Market Withdrawals,” published in the August issue, Cassie Frank and coauthors compare the number of approved prescription drugs that received black-box warnings or were withdrawn from the market for safety-related reasons prior to the 1992 Prescription Drug User Fee Act (PDUFA) with black-box warnings and safety-related withdrawals in the post-PDUFA era.

PDUFA for the first time authorized FDA to collect user fees from brand-name manufacturers that submitted New Drug Applications, with the funds being earmarked for more review staff (not until 2007 were funds also permitted to be used to expand post-approval safety surveillance capacity).

As a quid pro quo, the FDA was required to act on all new drugs within a fixed deadline: drugs given priority review designations because they were particularly promising therapies offering substantial improvements in treating serious conditions were to be reviewed within 6 months and standard review drugs were to be reviewed within 12 months (later shortened to 10 months in 2002). By all accounts, PDUFA substantially expedited the review process. The review times for new molecular entities decreased from an average of 33.6 months between 1978 and 1986 to about 10 months for drugs approved between 2001-2010.

Frank and coauthors found that drugs approved in the 16 years after PDUFA were more likely to have a black-box warning or be withdrawn from the market for safety reasons than drugs approved prior to PDUFA between 1979-1986 (26.7 percent vs. 21.2 percent; odds ratio 1.35, p <0.05).

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.