Bayesian joint modelling of benefit and risk in drug development

To gain regulatory approval, a new medicine must demonstrate that its benefits outweigh any potential risks, ie, that the benefit‐risk balance is favourable towards the new medicine. For transparency and clarity of the decision, a structured and consistent approach to benefit‐risk assessment that quantifies uncertainties and accounts for underlying dependencies is desirable. This paper proposes two approaches to benefit‐risk evaluation, both based on the idea of joint modelling of mixed outcomes that are potentially dependent at the subject level. Using Bayesian inference, the two approaches offer interpretability and efficiency to enhance qualitative frameworks. Simulation studies show that accounting for correlation leads to a more accurate assessment of the strength of evidence to support benefit‐risk profiles of interest. Several graphical approaches are proposed that can be used to communicate the benefit‐risk balance to project teams. Finally, the two approaches are illustrated in a case study using real clinical trial data.