The MCP-Mod approach from Bretz et al. (2005) has attracted considerable attention in recent years. The MCP part of MCP-Mod was originally developed to detect a dose response signal using a suitable trend test, but it is not appropriate to make a specific claim that the drug has a positive effect at some dose. In this presentation we provide a way to obtain confirmatory p-values for the dose response signal declaration as well as for the pairwise comparisons of individual doses against placebo. We apply the closed testing principle from Marcus et al. (1976) to the optimal contrasts tests based on a-priori information about plausible dose response shapes available at the planning stage of a clinical trial. We show that the contrast coefficients have to be optimized under suitable constraints to guarantee strong Type 1 error rate control at a pre-specified significance level. Motivated by a recent clinical trial, we evaluate the operating characteristics of the proposed methods in a comprehensive simulations study.

Bretz F, Pinheiro JC, Branson M. Combining multiple comparisons and modeling techniques in dose-response studies. Biometrics 2005, 61,738--748.

Marcus R, Eric P, Gabriel KR. On closed testing procedures with special reference to ordered analysis of variance. Biometrika 1976, 63, 655-660.