Multi-Regional Clinical Trials (MRCTs) play a central role in the development of new therapies by enabling the simultaneous evaluation of drug efficacy and safety across diverse global populations. Assessing the consistency of treatment effects across regions is a fundamental aspect of MRCTs. Existing methods typically focus on region-specific marginal treatment effects. However, when treatment effect heterogeneity arises due to effect-modifying baseline covariates, distributional differences in these covariates can lead to erroneous conclusions. In this paper, we explicitly account for this phenomenon in the consistency assessment by considering the conditional average treatment effect. We propose a two-step assessment strategy that complements existing methods and mitigates the impact of treatment effect heterogeneity. Results from numerical studies demonstrate the effectiveness of the proposed approach.

翻译：多区域临床试验（MRCTs）在新疗法开发中发挥着核心作用，它能够同时评估药物在不同全球人群中的疗效和安全性。评估区域间治疗效果的一致性是多区域临床试验的基本环节。现有方法通常关注区域特定的边际治疗效果。然而，当治疗效果异质性由效应修饰性基线协变量引起时，这些协变量的分布差异可能导致错误结论。本文在一致性评估中明确考虑了这种现象，通过引入条件平均治疗效果进行分析。我们提出了一种两步评估策略，该策略对现有方法形成补充，并减轻治疗效果异质性的影响。数值研究结果证明了所提方法的有效性。