Design and Analysis of Bridging Studies: 1st Edition (Hardback) book cover

Design and Analysis of Bridging Studies

1st Edition

Edited by Jen-pei Liu, Shein-Chung Chow, Chin-Fu Hsiao

Chapman and Hall/CRC

287 pages | 23 B/W Illus.

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As the development of medicines has become more globalized, the geographic variations in the efficacy and safety of pharmaceutical products need to be addressed. To accelerate the product development process and shorten approval time, researchers are beginning to design multiregional trials that incorporate subjects from many countries around the world under the same protocol.

Design and Analysis of Bridging Studies addresses the issues arising from bridging studies and multiregional clinical trials. For bridging studies, the book explores ethnic sensitivity, the necessity of bridging studies, types of bridging studies, and the assessment of similarity between regions based on bridging evidence. For multiregional clinical trials, the text considers regional differences, assesses the consistency of treatment effect across regions, and discusses sample size determination for each region.

Taking into account the International Conference Harmonisation (ICH) E5 framework for bridging studies, the book provides a unified summary of the growing literature and research activities in this area. It covers the regulatory requirements, scientific and practical issues, and statistical methodology for designing and evaluating bridging studies and multiregional clinical trials, with the goal of inspiring new research activities in the field.


"… a place to start acquiring an understanding of bridging and multi-regional studies and as a supplement to ICH-E5 and local region’s current regulatory implementation guidance. … this book is also intended to stimulate additional research in bridging and multi-regional trials and will be of interest to those looking for research topics."

—Scott D. Patterson, PhD, Pfizer, Vaccines Research & Development in Australian and New Zealand Journal of Statistics

Table of Contents

Bridging Diversity: Extrapolating Foreign Data to a New Region, Shein-Chung Chow and Chin-Fu Hsiao


Impact of Ethnic Differences

Regulatory Guidelines

Current Issues


Concluding Remarks

Aim and Structure of the Book

Two-Stage Designs of Bridging Studies, Chin-Fu Hsiao, Hsiao-Hui Tsou, Jen-pei Liu, and Yuh-Jenn Wu


Two-Stage Design for Bridging Studies

Group Sequential Approach to Evaluating Bridging Studies

Concluding Remarks

Consistency of Treatment Effects in Bridging Studies and Global Multiregional Trials, Weichung J. Shih and Hui Quan


Global Clinical Trial

Consistency in Making Inference Regarding the Overall Treatment Effect θ

Consistency as a Method for Region-Specific Registration

Other Considerations



Assessing Similarity Using the Reproducibility and Generalizability Probabilities and the Sensitivity Index, Shein-Chung Chow, Ying Lu, and Lan-Yan Yang


Criteria for Assessing Similarity

Reproducibility and Generalizability

Assessing the Similarity-Based Sensitivity Index

Concluding Remarks

Combining Information in Clinical Drug Development: Bridging Studies and Beyond, Kuang-Kuo Gordon Lan and Jose Pinheiro


Leveraging Existing Information in Bridging Studies

Application: Bridging of Blood Pressure Drug


A Bayesian Approach for Evaluation of Bridging Studies, Chin-Fu Hsiao, Hsiao-Hui Tsou, Jen-pei Liu, and Yuh-Jenn Wu


Mixture of Prior Information

Determination of Sample Size


Concluding Remarks

Issues of Sample Size in Bridging Trials and Global Clinical Trials, Hsien-Ming James Hung, Sue-Jane Wang, and Robert O’Neill

Issues of Sample Size Planning for Bridging Trial

Issues of Sample Size Planning in Global Clinical Trial

Impacts of Consistency Assessment on Sample Size


Design and Sample Size Considerations for Global Trials, Christy Chuang-Stein, Yoichi Ii, Norisuke Kawai, Osamu Komiyama, and Kazuhiko Kuribayashi


Points to Consider When Designing a Multiregional Trial

Determination of Regional Sample Size in a Multiregional Study

Additional Analysis to Estimate Treatment Effects in Different Regions

Real-Time Monitoring of Multiregional Trials

Concluding Remarks

Application of Genomic Technologies for Bridging Strategy Involving Different Race and Ethnicity in Pharmacogenomics Clinical Trials, Sue-Jane Wang


Pharmacogenomics and Pharmacogenetics


Bridging Study Evaluation

Challenges of Bridging Strategy in Pharmacogenomics

Concluding Remarks

Interaction Effects in Bridging Studies, Eric Tsung-Cheng Hsieh and Jen-pei Liu


Noninferiority Hypothesis for Treatment Similarity

Statistical Testing Procedures

Simulation Studies

Numerical Examples

Discussion and Final Remarks

Multiregional Clinical Trials, Yi Tsong and Hsiao-Hui Tsou


Different Regional Requirements

Bridging the Overall Treatment Effect to Regions


Multiregional Clinical Trials for Global Simultaneous Drug Development in Japan, Kihito Takahashi, Mari Ikuta, and Hiromu Nakajima


Drug Lag

MRCTs as a Solution to Drug Lag

Improvements in Clinical Trial Environment in Japan

Growing Trends of MRCTs in Japan

MRCTs in the Field of Oncology

MRCTs in the Field of CVM

Issues in MRCTs

Future Prospects

Feasibility and Implementation of Bridging Studies in Taiwan, Mey Wang, Yeong-Liang Lin, and Herng-Der Chern


Regulatory History of Bridging Strategy

Assessment Experiences Based on ICH E5

Bayesian Statistical Approach to Bridging Studies

Designing an External (Supplemental) Bridging Study

Concluding Remarks


References appear at the end of each chapter.

About the Editors

Jen-pei Liu is a professor in the Division of Biometry, Department of Agronomy, and Institute of Epidemiology and Preventative Medicine at National Taiwan University. He is also an adjunct investigator in the Institute of Population Health Sciences at the National Health Research Institutes in Taiwan. A fellow of the ASA, Dr. Liu is an associate editor of the Journal of Biopharmaceutical Statistics and an editor of the Chapman & Hall/CRC Biostatistics Series. He has authored ten books, over 120 peer-reviewed research articles, and over 40 book chapters. His research interests include statistical methodology in bioequivalence evaluation, clinical trials, equivalence and noninferiority testing, bridging testing, statistical quality control in biopharmaceutical products, diagnostic testing, statistical QA/QC for biochip diagnostic products, and evaluation of substantial equivalence in GMO crops and food.

Shein-Chung Chow is a professor in the Department of Biostatistics and Bioinformatics at Duke University School of Medicine. Dr. Chow is also a professor of clinical sciences at Duke–National University of Singapore Graduate Medical School. He is the editor-in-chief of the Journal of Biopharmaceutical Statistics and editor-in-chief of the Chapman & Hall/CRC Biostatistics Series. He has authored or co-authored over 200 papers and 19 books, including Adaptive Design Methods in Clinical Trials, Second Edition, Handbook of Adaptive Designs in Pharmaceutical and Clinical Development, and Controversial Statistical Issues in Clinical Trials. A fellow of the ASA and member of the ISI, Dr. Chow has received the ASA Chapter Service Recognition Award, the DIA Outstanding Service Award, and the ICSA Extraordinary Achievement Award.

Chin-Fu Hsiao is an investigator in the Institute of Population Health Sciences at the National Health Research Institutes in Taiwan. Dr. Hsiao is also an adjunct associate professor at National Chiao Tung University. His research interests encompass Bayesian analysis, clinical trials, and genetic study.

About the Series

Chapman & Hall/CRC Biostatistics Series

Learn more…

Subject Categories

BISAC Subject Codes/Headings:
MATHEMATICS / Probability & Statistics / General
MEDICAL / Pharmacology
MEDICAL / Biostatistics