Statistical considerations on implementing the MCP-Mod method for binary endpoints in clinical trials.

Abstract The Multiple Comparison Procedure – Modelling (MCP-Mod) method was qaulified by regulatory agencies (e.g., EMA in 2014 and FDA in 2016) as an efficient statistical method for Phase 2 dose-finding studies when there is uncertainty about dose-response relationship. As this is a relatively new approach, there is limited literature providing practical guidance on its application. In this paper, we evaluated the performance of the MCP-Mod method for clinical trials with a binary primary endpoint, focusing on (1) the impact of sample size, data variability and treatment effect size on the performance of the MCP-Mod, (2) the impact of candidate model mis-specification, and (3) optimal sample allocation under a fixed sample size. The evaluation was performed via simulations under different scenarios.