Risk management policy and black-box warnings: a qualitative analysis of US FDA proceedings

Drug Saf. 2009;32(11):1057-66. doi: 10.2165/11316670-000000000-00000.


Background: The US FDA increasingly applies risk management to drug safety policy. Little is known about the process by which the FDA approves labelling changes. Although advisory committees can recommend any of the risk management tools, including the use of 'black-box warnings', it is unknown whether they deliberate on these questions or how they apply the principles of risk minimization or management during their considerations of drug licensing.

Objective: To examine the process by which risk management is considered by the FDA, including the role of FDA advisory committees. We also aimed to identify and describe drug labelling changes and additions, including the prevalence of black-box warnings.

Methods: We electronically obtained publicly available information regarding drug approvals, drug revisions and advisory committee meetings over 3 years (2004-6) from the FDA. Data in the form of meeting transcripts and full histories of labelling changes were collected on drugs discussed by advisory committees. We then searched and qualitatively analysed the meeting transcripts to identify themes in the discussion. We also created a database of all prescription drug labelling changes for 3 years and examined which drugs have had the most changes. We describe the risk management consideration process and report the frequency and characteristics of labelling changes. Excerpts from the transcripts are selected to illustrate both typical and atypical features of the discussion.

Findings: A total of 174 black-box changes were made in the 3-year period of our study, of which 77 were new black-box warnings and 97 were revisions in black-box warnings. Of 77 new black-box warning additions, only 11 drugs were discussed by the advisory committees. Of the 17 most frequently revised drug labels in these 3 years, two were discussed in the advisory committee meetings. Advisory meeting discussions revealed confusion about black-box warnings and emphasized potential consequences of the warnings rather than their content.

Conclusion: The safety labelling of drugs on the market is changed often. Panels of advisors consider only a few drugs, rarely discuss the labelling requirements, and display confusion about applying black-box warnings. The creation and application of black-box warnings on prescription medications should receive closer attention from the FDA and its advisors.

MeSH terms

  • Advisory Committees / organization & administration
  • Drug Labeling / legislation & jurisprudence*
  • Drug-Related Side Effects and Adverse Reactions
  • Health Policy / legislation & jurisprudence
  • Humans
  • Legislation, Drug / organization & administration
  • Risk Management / methods*
  • United States
  • United States Food and Drug Administration*