Sample Size Allocation in Multiregional Dose-Finding Study Using MCP-Mod

Simultaneous global drug development with multiregional studies is becoming a common strategy for increasing efficiency of the development process. In particular, multiregional dose-finding studies can be informative to identify inter-ethnic difference in dose-response relationships early in development. An application of MCP-Mod to multiregional studies is discussed in this article. We consider sample size allocation to one specific region and provide three methods for demonstrating consistency in the dose-response relationship between the entire population and one specific region: two methods use contrast statistics to show consistency in dose-response signals, and the third method uses the maximum absolute difference between two dose-response curves to show consistency in the dose-response profiles. The proposed methods do not require studies to have sufficient power to detect a truly consistent dose-response relationship in a confirmatory manner, but rather to allow for quantitative design considerations that can ensure such a relationship is observed at the end of the study with acceptable probability. The three methods are illustrated through an anti-anxiety drug example, resulting in a recommended proportion of 20% for subjects in one specific region. The illustration indicates the recommended proportion could vary depending on the total study sample size.