FDA Determines Multiple Comparison Procedure-Modeling (MCP-Mod) Statistical Approach is Fit-for-Purpose

On May 26, 2016, FDA determined that the Multiple Comparison Procedure – Modeling (MCP-Mod) statistical approach is fit-for-purpose . Fit-for-purpose designation provides a pathway for FDA to assess and comment on the utility of drug development tools. Such tools are made publicly available in an effort to facilitate appropriate utilization in drug development.

Dose selection for phase 3 trials is a critical component in drug development that should be based on the dose (concentration) response relationship obtained from earlier studies (phase 1 and phase 2). MCP-Mod is a hybrid approach that combines hypothesis testing and modeling to analyze phase 2 dose-ranging studies with the purpose of finding suitable dose(s) for confirmatory phase 3 trials. The first step of the procedure (MCP-step) is used to assess presence of a dose-response signal using a trend test deducted from a set of prespecified candidate models. The second step (Mod-step) relies on parametric modeling or model averaging to find the “optimal” dose for confirmatory trials. The approach facilitates more informative phase 2 trial design by encouraging:

• testing three or more active and well separated doses
• investigating doses on the ascending part of the dose-response curve
• interpolation and extrapolation to select dose(s) for pivotal trial(s)

The MCP-Mod method was jointly evaluated by the Office of Biostatistics and Office of Clinical Pharmacology within CDER’s Office of Translational Sciences. MCP-Mod was assessed based on metrics relevant to the analysis of dose ranging trials. These metrics included type I error rate, power to detect a significant dose-response shape, and the power to find the minimal effective dose. The MCP-Mod method was found adequate and appropriate for dose selection based on dose-response data.http://www.fda.gov/Drugs/DevelopmentApprovalProcess/ucm505485.htm

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