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

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.