A new framework to address challenges in quantitative benefit-risk assessment for medical products.

Abstract In recent years, there has been a proliferation of regulatory and industry-wide initiatives on structured benefit-risk (BR) assessment. Examples of structured BR frameworks include the PrOACT-URL (Problem formulation, Objectives, Alternatives, Consequences, Trade-Offs, Uncertainties, Risk Attitude and Linked Decisions) from European Medicines Agency Work Package 3, multiple U.S. Food and Drug Administration guidance documents on benefit-risk assessment for medical devices, and U.S. Food and Drug Administration implementation plans for benefit-risk assessment in drug regulatory decision-making. In June 2016, the ICH Expert Working Group finalized the Common Technical Document (CTD) Section 2.5.6 on Benefit-Risk Evaluations. As a result of these efforts, the uptake and utilization of structured benefit-risk (BR) assessments has been increasing. However, the aforementioned BR frameworks are mostly qualitative in nature, and the utility of quantitative BR approaches has not been systemically explored, creating uncertainty about settings in which quantitative BR assessment (qBRA) could be optimally applied. In this paper, we will provide an overview of the current qBRA methods, discuss challenges of qBRA, and describe a structural qBRA framework. The performance of the described qBRA framework will be evaluated by simulations based on a case study.