Adjustment for Inconsistency in Adaptive Phase 2/3 Designs with Dose Optimization

Abstract: Adaptive Phase 2/3 designs hold great promise in contemporary oncology drug development, especially when limited data from Phase 1 dose-finding is insufficient for identifying an optimal dose. However, there is a general concern about inconsistent results before and after the adaptation. The imperfection in dose selection further complicates the issue. In this paper, we explicitly incorporate the concerns about inconsistency into the statistical analysis under three hypothesis testing strategies. This investigation paves the way for further research in a less explored area.