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Quantitative benefit risk analysis for prophylactic vaccines in the context of FDAs benefit risk framework
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  • Published: 05 February 2026

Quantitative benefit risk analysis for prophylactic vaccines in the context of FDAs benefit risk framework

  • Hong Yang1,
  • Osman N. Yogurtcu1,
  • Ujwani Nukala1,
  • Patrick R. Funk1,
  • Hector S. Izurieta2 &
  • …
  • Richard A. Forshee1,3 

npj Vaccines , Article number:  (2026) Cite this article

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Computational biology and bioinformatics
  • Drug discovery
  • Health care
  • Immunology
  • Medical research

Abstract

Benefit-risk assessment (BRA) plays a vital role in the development and approval of drugs and biologics, including vaccines. The U.S. Food and Drug Administration recently published the final guidance “Benefit-Risk Assessment for New Drugs and Biological Products”, which presents a structured framework for evaluating the benefit-risk (BR) of drugs and biological products and encourages the use of quantitative BR analysis (qBRA) to support complex decision-making. Unique challenges arise when assessing the BR of prophylactic vaccines, including the extrapolation of clinical trial data to real-world outcomes. To address these challenges, qBRA has been used to assist in some cases of decision-making related to vaccines. This article explores key steps and considerations for the qBRA of vaccines within the FDA BR framework. We explore the processes of “Framing the Research Question and Scope,” “Identifying Key Benefit and Risk Endpoints,” “Selecting the Quantitative Approach and Characterization of Uncertainties,” “Gathering Data and Establishing qBRA Model Assumptions,” and “Interpreting and Communicating the BRA Results,” highlighting major considerations for each step. By carefully considering these processes and their challenges, we aim to help develop qBRAs that effectively inform decisions, ensuring that the benefits of authorized and licensed vaccines outweigh their risks.

Data availability

Not applicable.

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Acknowledgements

Authors’ contributions are an informal communication and represent their own best judgment. These comments do not bind or obligate FDA. The authors gratefully acknowledge Dr. Xinyi Ng and Dr. Maria Allende (US FDA CBER) for their constructive comments, which significantly improved the quality of this manuscript. Funding Not applicable.

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Authors and Affiliations

  1. Office of Biostatistics and Pharmacovigilance, Center for Biologics Evaluation and Research, US FDA, Silver Spring, MD, USA

    Hong Yang, Osman N. Yogurtcu, Ujwani Nukala, Patrick R. Funk & Richard A. Forshee

  2. Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, US FDA, Silver Spring, MD, USA

    Hector S. Izurieta

  3. Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, US FDA, Silver Spring, MD, USA

    Richard A. Forshee

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  1. Hong Yang
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Contributions

H.Y., O.N.Y., and U.N. contributed to the conception and design of the paper, draft and final review, P.R.F. and H.S.I. contributed to edit and final review, R.A.F. contributed to the final review. All authors read and approved final version of the manuscript.

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Yang, H., Yogurtcu, O.N., Nukala, U. et al. Quantitative benefit risk analysis for prophylactic vaccines in the context of FDAs benefit risk framework. npj Vaccines (2026). https://doi.org/10.1038/s41541-025-01342-3

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  • Received: 21 November 2025

  • Accepted: 03 December 2025

  • Published: 05 February 2026

  • DOI: https://doi.org/10.1038/s41541-025-01342-3

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