FDA’s Benefit–Risk Framework for Human Drugs and Biologics: Role in Benefit–Risk Assessment and Analysis of Use for Drug Approvals

Background Structured, descriptive approaches are utilized by drug regulatory agencies to support and communicate approval decisions about human drugs and biologics. The US Food and Drug Administration (FDA) uses the Benefit–Risk Framework (BRF), which has been integrated into its drug review process. This paper reviews how FDA review teams have used the BRF to communicate approval decisions. Methods This paper (1) uses content analysis to systematically review the decision factors communicated by FDA review teams in all BRFs associated with novel drugs approved by FDA in 2017–2018 and (2) presents a case study about how the BRF was used for three drugs approved for HIV-1 in 2018–2019. Results The content analysis found most BRFs for novel drug approvals communicate what we call an “urgent” context and complicating decision factors around benefit and/or risk; the HIV-1 case study highlights the flexibility of the structured BRF tool. Conclusions FDA’s BRF provides a flexible mechanism for communicating important decision factors, allowing it to support the diversity of drug approval decisions made by FDA.