Recent advances in biomedical research have identified an increasing number of biomarkers associated with heterogeneity in patient responses to medical treatments. When a treatment is suspected to benefit certain patient subpopulations, adaptive enrichment designs may be more efficient and ethical. In such designs, an interim analysis is incorporated during the trial to select patient subpopulations for which the experimental treatment appears promising, according to predefined subpopulation selection rules. However, data-dependent selection can induce selection bias, causing conventional maximum likelihood estimators (MLEs) to overestimate the treatment effect in the selected patient subgroup. Existing inference methods for addressing this bias are typically rule-specific, highlighting the need for an estimation framework that accommodate a broader class of subpopulation selection rules. In this work, we define a general class of subpopulation selection rules based on the sample space partition condition and provide a systematic derivation that yields a unified formula for the Uniformly Minimum Variance Conditional Unbiased Estimator (UMVCUE). This generality allows our formulation to encompass a wide spectrum of adaptive enrichment designs, eliminating the necessity for case-specific derivations for each new design. Extensive simulations confirm the unbiasedness of the proposed UMVCUE, ensuring that therapeutic benefits are not overestimated. By bridging the gap between flexible interim subpopulation selection and rigorous statistical inference, our framework has the potential to facilitate the implementation of diverse subpopulation selection rules with greater ease in real-world trials and promote more efficient and ethical drug development.

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