A Workflow for Evaluating Regional Treatment Effect Heterogeneity in Multi-Regional Clinical Trials

Fuente: arXiv
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Hauptverfasser: Zhang, Cong, Long, Meihua, Zheng, Tianyu, Sechidis, Konstantinos, Liu, Xiaoni, Sun, Sophie, Chen, Yao, Zhang, Xinyi, Kaneko, Shuhei, Bornkamp, Björn, Hou, Yan
Format: Preprint
Veröffentlicht: 2026
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author Zhang, Cong
Long, Meihua
Zheng, Tianyu
Sechidis, Konstantinos
Liu, Xiaoni
Sun, Sophie
Chen, Yao
Zhang, Xinyi
Kaneko, Shuhei
Bornkamp, Björn
Hou, Yan
author_facet Zhang, Cong
Long, Meihua
Zheng, Tianyu
Sechidis, Konstantinos
Liu, Xiaoni
Sun, Sophie
Chen, Yao
Zhang, Xinyi
Kaneko, Shuhei
Bornkamp, Björn
Hou, Yan
contents Multi-regional clinical trials (MRCTs) enable efficient global drug development by assessing treatment effects across regions within a single protocol. While powered for overall efficacy, MRCTs are typically not designed to provide confirmatory evidence on regional differences, making an assessment of observed regional heterogeneity largely exploratory and susceptible to sampling variability. Despite this challenge, understanding regional heterogeneity remains important for interpretation and regulatory decision-making. This paper proposes a structured, question-driven framework to guide exploratory assessments of regional heterogeneity in MRCTs. We formulate four key questions to clarify the objectives of such analyses and propose a set of statistical methods to address them. Simulation studies evaluate performance under scenarios with no heterogeneity and heterogeneity driven by observed or unobserved treatment effect modifiers, illustrating how a structured approach can support transparent and cautious interpretation.
format Preprint
id arxiv_https___arxiv_org_abs_2605_16885
institution arXiv
publishDate 2026
record_format arxiv
spellingShingle A Workflow for Evaluating Regional Treatment Effect Heterogeneity in Multi-Regional Clinical Trials
Zhang, Cong
Long, Meihua
Zheng, Tianyu
Sechidis, Konstantinos
Liu, Xiaoni
Sun, Sophie
Chen, Yao
Zhang, Xinyi
Kaneko, Shuhei
Bornkamp, Björn
Hou, Yan
Applications
Methodology
Multi-regional clinical trials (MRCTs) enable efficient global drug development by assessing treatment effects across regions within a single protocol. While powered for overall efficacy, MRCTs are typically not designed to provide confirmatory evidence on regional differences, making an assessment of observed regional heterogeneity largely exploratory and susceptible to sampling variability. Despite this challenge, understanding regional heterogeneity remains important for interpretation and regulatory decision-making. This paper proposes a structured, question-driven framework to guide exploratory assessments of regional heterogeneity in MRCTs. We formulate four key questions to clarify the objectives of such analyses and propose a set of statistical methods to address them. Simulation studies evaluate performance under scenarios with no heterogeneity and heterogeneity driven by observed or unobserved treatment effect modifiers, illustrating how a structured approach can support transparent and cautious interpretation.
title A Workflow for Evaluating Regional Treatment Effect Heterogeneity in Multi-Regional Clinical Trials
topic Applications
Methodology
url https://arxiv.org/abs/2605.16885