Benefit-Risk Assessment of Medical Products Using Bayesian Multi-Criteria Augmented Decision Analysis (MCADA) for Clinical Development

Multi-criteria decision analysis (MCDA) is a benefit-risk assessment tool that evaluates multiple competing benefit and risk endpoints simultaneously. MCDA has the potential to aid sponsors in making effective and informed go/no-go decisions for clinical development programs. MCDA involves assigning weights to benefit and risk endpoints based on their relative importance (i.e., utility weight) and using them to compute a single utility score that represents the overall benefit-risk profile of the treatment. However, to date, MCDA applications have not been appropriate for time-to-event data. In this paper, we introduce a novel framework known as Bayesian Multi-Criteria Augmented Decision Analysis (MCADA) that extends existing probabilistic MCDA methods to encompass time-to-event and ordinal outcomes while incorporating linear and novel non-linear functions in utility aggregation. This paper provides a comprehensive description of the statistical methodology behind the MCADA framework and demonstrates its application using a simulation study, as well as two clinical trials using IPD and aggregate data. Our simulation study found that MCADA generally achieves higher power than the existing MCDA methods due to avoidance of loss of information that occurs when survival and ordinal outcomes are dichotomized. Our two case studies show that the MCADA framework can be effectively used to produce a single utility score that reflects the overall benefit-risk profile of a treatment using both IPD and aggregate data from trials. MCADA broadens the horizon of the current MCDA framework by accommodating a wider range of data types and utility functions in the utility aggregation process.