Calculation of Phase 2 dose-finding study sample size for reliable Phase 3 dose selection

Sample sizes of Phase 2 dose-finding studies, usually determined based on a power requirement to detect a significant dose–response relationship, will generally not provide adequate precision for Phase 3 target dose selection. We propose to calculate the sample size of a dose-finding study based on the probability of successfully identifying the target dose within an acceptable range (e.g., 80%–120% of the target) using the multiple comparison and modeling procedure (MCP-Mod). With the proposed approach, different design options for the Phase 2 dose-finding study can also be compared. Due to inherent uncertainty around an assumed true dose–response relationship, sensitivity analyses to assess the robustness of the sample size calculations to deviations from modeling assumptions are recommended. Planning for a hypothetical Phase 2 dose-finding study is used to illustrate the main points. Codes for the proposed approach is available at https://github.com/happysundae/posMCPMod .