In a global clinical development strategy, multiregional clinical trials (MRCTs) are vital in the development of innovative medicines. Multiregional Clinical Trials for Simultaneous Global New Drug Development presents a comprehensive overview on the current status of conducting MRCTs in clinical development. International experts from academia, industry, and health organizations address various aspects of the important problems in global clinical development and MRCTs.
The book first provides a high-level introduction to the context, motivation, opportunities, and challenges in simultaneous global clinical development using MRCTs. It then focuses on the design, monitoring, and analysis/interpretation of MRCTs. The book concludes with an examination of the latest research topics from MRCT perspectives, such as special considerations by local health authorities, health economic evaluations, benefit-risk assessment, and medical devices.
Explaining how to design, conduct, and interpret MRCTs, this book will help biostatisticians working in the late-stage clinical development of medical products. It will also be useful for statisticians and clinicians in the biopharmaceutical industry, regulatory agencies, and medical research institutes.
Table of Contents
Simultaneous Global Development
The Journey to Multiregional Clinical Trials in Support of Simultaneous Global Product Development
General Principles and Considerations in Multiregional Clinical Trials for Simultaneous Global New Drug Development
Ekopimo Ibia and Bruce Binkowitz
Bridging Studies versus Multiregional Trials
Weichung J. Shih
Multiregional Clinical Trial: Design Considerations
Multiregional Clinical Trials: Assessing Consistency of Treatment Effect
Joshua Chen and Hongwei Wang
Regulatory Perspectives: Different Requirements/Endpoints and Needs for Harmonization
Cynthia J. Girman and Bruce Binkowitz
Intrinsic and Extrinsic Factors and Rationales to Be Considered When Defining Regions
Models and Sample Sizes for Multiregional Clinical Trials
Hui Quan and Mingyu Li
Multiregional Clinical Trials in Oncology Drug Development
A Few More Considerations in Multiregional Clinical Trials on Regional Differences
Bo Yang and Yijie Zhou
Optimal Multiregional Clinical Trials
Zhaoyang Teng and Mark Chang
Implementation of Multiregional Clinical Trial Design
Xuezhou Mao and Mingyu Li
Multiregional Clinical Trial: Data Monitoring Committee and Monitoring Regional Difference
Independent Data Monitoring Committees in Multiregional Clinical Trials
Monitoring Regional Difference Based on Blinded Data in Multiregional Clinical Trials
Adaptive Multiregional Clinical Trials
Zhaoyang Teng and Mark Chang
Multiregional Clinical Trial: Analysis, Reporting, and Interpretation
Lessons Learned and Recommendations Regarding Multiregional Clinical Trials from a Well-Practiced Industry Statistician
Quantification of Regional Treatment Effects for Multiregional Clinical Trials
Hui Quan and Xuezhou Mao
Multiregional Clinical Trials: Country-Specific Assessment
Joshua Chen and Xuezhou Mao
Multiregional Outcome Trial for a Multivalent Human Papillomavirus Vaccine: A Case Study
Oliver M. Bautista, Erin Moeller, and Alain Luxembourg
Multiregional Clinical Trial: Latest Development and Trend
The Discrete Random-Effects Model: Assessing Benefit and Consistency of Treatment Effect
Hsiao-Hui Tsou, K.K. Gordon Lan, Jung-Tzu Liu, and Chin-Fu Hsiao
New Drug Development Paradigms in China: Simultaneous Global Drug Development Program
Gang Chen, Qin Huang, Frank Shen, Zhilong Yuan, and Dayao Zhao
Special Considerations for Emerging Markets
Gang Li and Jun Zhao
A Predictive Bayesian Approach to the Design and Analysis of Bridging Studies
A. Lawrence Gould and William W.B. Wang
Multiregional Clinical Trial: Japanese Viewpoint
Madoka Takeuchi and Masahiro Takeuchi
Special Considerations for Medical Devices: An Overview
Yunling Xu, Nelson Lu, and Gerry Gray
Use of Multinational Randomized Clinical Trials in Economic Evaluations of Health Care
Joseph Heyse, Jieling Chen, and John Cook
Regional Benefit and Risk Evaluations
Soo Peter Ouyang and Hui Quan
Joshua Chen is the global head of biostatistics and programming at Sanofi Pasteur. He previously worked on clinical development of small molecules, biologics, and vaccines at Merck Research Laboratories. His experience spans many therapeutic areas with a major focus on human vaccines and antiviral drugs. He has extensive experience in the study, design, conducting, and reporting of international clinical trials from proof of concept through regulatory approvals and life cycle management. His primary research interest is clinical trial designs, including group sequential methods, adaptive designs, and multiregional clinical trials (MRCTs). Dr. Chen was a colead of the cross-industry MRCT Consistency Working Group under PhRMA (2008–2011) and the Society for Clinical Trials (2012–2014). He earned his PhD in statistics from the University of Wisconsin–Madison.
Hui Quan is an associate vice president and global head of the methodology group in the Biostatistics and Programming Department of Sanofi–Aventis. A fellow of the American Statistical Association, he has 24 years of pharmaceutical industry experience in many therapeutic areas ranging from early phase to phase IV studies. He has published 82 papers, including 59 statistical papers. His research interests include multivariate analysis, safety analysis, multiplicity adjustment, missing handling, adaptive design, integrated data analysis, modeling and simulation, benefit/risk assessment, and MRCTs. Dr. Quan was a colead of the MRCT Consistency Assessment Working Group under PhRMA (2008–2011) and the Society for Clinical Trials (2012–2014). He earned his PhD in statistics from Columbia University.
This book consolidates current state of knowledge regarding relevant topics on MRCTs (design, operation, and analysis/interpretation) into well-organized chapters. This book should serve as a useful source of information to anyone who plans to work or is working on MRCTs. There are many on-going challenges and we also hope it will stimulate further research in MRCTs.
~Nobushige Matsuoka, PhD and Norisuke Kawai, PhD, Pfizer Japan Inc.
" . . . Contributors to this book are among the best experts in their corresponding fields. . . Most chapters are short, with about 20 pages including references. This length of chapter makes the book easy to read and easy to follow. Concepts involving design, conduct, and analysis of MRCT are not simple, but this book successfully presents all of these topics—setting the stage and drilling down to a reasonable depth, without unnecessary detail. It also introduces many real world examples to help readers understand some of the difficult concepts. . . Each chapter introduces a stand-alone, self-contained topic. Cross-referencing of chapters is rarely needed, but is provided where appropriate. I learned a lot from this book, especially that issues arising in MRCT are much more difficult than issues in multi-center trials, from which much of my experience with clinical trials comes."
~Naitee Ting, Boehringer Ingelheim Pharmaceuticals, Inc.
"The editors have collected chapters and sections contributed by many authors, with each addressing a different important problem in global clinical development and MRCTs. The contributions to individual topics from academia, industry, and health authorities around the globe, strengthen the documentation greatly . . . I fully endorse the views of the editors that biostatisticians working in the area of randomized controlled trials in general, and MRCTs in particular, will find this book a useful reference."
~Sada Nand Dwivedi, International Society for Clinical Biostatistics