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



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.


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.


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.


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.

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We thank the Division of Antiviral Products (Office of New Drugs, CDER, FDA) for helpful discussion to inform the case study. We also thank staff and leadership in the Office of New Drugs (CDER, FDA) for helpful feedback.


No funding was obtained for this research.

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All authors had substantial contributions to all aspects of authorship, including conception and design, data acquisition, analysis, and interpretation; drafting and revising the work; final approval of the published version; and agreement to be accountable for all aspects of the work.

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Correspondence to Leila Lackey.

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The authors are employed by the Center for Drug Evaluation and Research at the FDA. They have no other conflicts to disclose. This publication reflects the views of the authors and should not be construed to represent FDA’s views or policies.

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Lackey, L., Thompson, G. & Eggers, S. FDA’s Benefit–Risk Framework for Human Drugs and Biologics: Role in Benefit–Risk Assessment and Analysis of Use for Drug Approvals. Ther Innov Regul Sci 55, 170–179 (2021).

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  • Benefit–risk assessment
  • FDA
  • Content analysis
  • HIV
  • Decision-making