Multi-stage adaptive enrichment trial design with subgroup estimation

We consider the problem of estimating the best subgroup and testing for treatment effect in a clinical trial. We define the best subgroup as the subgroup that maximizes a utility function that reflects the trade-off between the subgroup size and the treatment effect. For moderate effect sizes and sample sizes, simpler methods for subgroup estimation worked better than more complex tree-based regression approaches. We propose a three-stage design with a weighted inverse normal combination test to test the hypothesis of no treatment effect across the three stages.