All Times EDT
Keywords: benefit-risk assessment; treatment-and-disease-burden; win-statistics
A fundamental problem in the regulatory evaluation of a therapy is assessing whether the benefit outweighs the associated risks. This work proposes designing a trial that assess a composite endpoint consisting of benefit and risk, hence, making the core of the design of the study, to assess benefit and risk. The assessment of risk is based on a composite score obtained from pre-defined adverse events of interest. This composite score incorporates full aspects of adverse events of interest (i.e, the incidence, severity, and duration of the events). We call this score the treatment-and-disease-burden score. After specifying the priorities between the components of the composite endpoint, a win-statistic is used to assess difference between treatments in this composite endpoint. The power and sample size requirements of such a trial design are explored via simulation. Finally, using Dupixent published adult study results, we show how we can design a paediatric trial where the primary outcome is a composite of prioritized outcomes consisting of efficacy endpoints and the treatment-and-disease-burden endpoint. The resulting trial design can potentially substantially reduce sample size compared to a trial designed to assess the co-primary efficacy endpoints, therefore it may address the challenge patient recruitment for paediatric studies.