Risk Management Policy and FDA Black Box Warnings

Background/Objective: The Food and Drug Administration is applying risk management principles to drug safety policy. In the context of recent and ongoing safety concerns with prescription drugs, we studied the drug licensing process and examined safety labeling policy. We looked for trends in new drug approvals and safety-related labeling changes made by the FDA with a focus on black box warnings, and investigated the role of advisory committees in the policy decisions.

Methods: We obtained publicly available information regarding drug approvals, drug revisions and advisory committee meetings over three years (2004-2006) from the FDA electronically. We collected data on drugs discussed by advisory committees and then searched the meeting transcripts for keywords. We collected data on three years of drugs that have added or revised a black box warning label. We also created a database of all prescription drug labeling changes for three years and examined which drugs have had the most changes. We then compared and analyzed this data using qualitative methods.

Results: The total number of new drugs discussed by FDA advisory committees in three years was 31, of which 4 were approved with black box warnings and 9 were approved without black box warning. System-wide a total of 174 black box changes were made in these 3 years, out of which 77 were new black box warnings and 97 were revisions in black box warnings. Out of 77 new black box additions, only 11 drugs were discussed by the advisory committees. Of the 17 most frequently revised drug labels in these 3 years, 6 carry a black box warning and 2 were discussed in the advisory committee meetings. Transcripts of advisory discussions revealed confusion about black box warnings.

Conclusion: The safety labeling of drugs on the market is changed often. Panels of advisors only consider a few drugs, and rarely discuss the labeling requirements. The role of public expert advisory committees in issuing the strongest drug label warnings is inconsistent. Strong black box warnings are rarely applied to new drugs. Many drugs with frequent safety-related label changes do not yet have black box warnings. A policy rooted in risk management seems to facilitate keeping drugs with questionable safety on the market. Data collection from the FDA for public health research presents many challenges.