Group-Sequential Clinical Trials with Multiple Co-Objectives

1. Front Matter

   Pages i-ix

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2. Introduction

   • Toshimitsu Hamasaki, Koko Asakura, Scott R. Evans, Toshimitsu Ochiai

   Pages 1-14

3. Interim Evaluation of Efficacy in Clinical Trials with Two Co-primary Endpoints

   • Toshimitsu Hamasaki, Koko Asakura, Scott R. Evans, Toshimitsu Ochiai

   Pages 15-39

4. Sample Size Recalculation in Clinical Trials with Two Co-primary Endpoints

   • Toshimitsu Hamasaki, Koko Asakura, Scott R. Evans, Toshimitsu Ochiai

   Pages 41-49

5. Interim Evaluation of Efficacy or Futility in Clinical Trials with Two Co-primary Endpoints

   • Toshimitsu Hamasaki, Koko Asakura, Scott R. Evans, Toshimitsu Ochiai

   Pages 51-65

6. Interim Evaluation of Efficacy in Clinical Trials with Two Primary Endpoints

   • Toshimitsu Hamasaki, Koko Asakura, Scott R. Evans, Toshimitsu Ochiai

   Pages 67-80

7. Group-Sequential Three-Arm Non-inferiority Clinical Trials

   • Toshimitsu Hamasaki, Koko Asakura, Scott R. Evans, Toshimitsu Ochiai

   Pages 81-95

8. Future Developments

   • Toshimitsu Hamasaki, Koko Asakura, Scott R. Evans, Toshimitsu Ochiai

   Pages 97-102

9. Back Matter

   Pages 103-113

   PDF

This book focuses on group sequential methods for clinical trials with co-primary endpoints based on the decision-making frameworks for: (1) rejecting the null hypothesis (stopping for efficacy), (2) rejecting the alternative hypothesis (stopping for futility), and (3) rejecting the null or alternative hypothesis (stopping for either futility or efficacy), where the trial is designed to evaluate whether the intervention is superior to the control on all endpoints. For assessing futility, there are two fundamental approaches, i.e., the decision to stop for futility based on the conditional probability of rejecting the null hypothesis, and the other based on stopping boundaries using group sequential methods. In this book, the latter approach is discussed. The book also briefly deals with the group sequential methods for clinical trials designed to evaluate whether the intervention is superior to the control on at least one endpoint. In addition, the book describes sample size recalculation and the resulting effect on power and type I error rate. The book also describes group sequential strategies for three-arm clinical trials to demonstrate the non-inferiority of experimental intervention to actively control and to assess the assay sensitivity to placebo control.

• Group Sequential Designs
• Interim Analysis
• Multiple Endpoints
• Noninferiority
• Sample Size Calculation
• Sample Size Recalculation

“This book is a highly stimulating read for anyone who is interested in group-sequential trials, or anybody who wishes to learn about how studies with multiple endpoints can be made more efficient.” (Michael J. Grayling, Technometrics, Vol. 60 (3), 2018)​

• Department of Data Science, Natl Cerebral & Cardiovascular Ctr, Suita, Japan

  Toshimitsu Hamasaki

• Department of Data Science, National Cerebral & Cardiovascular Ctr, Suita, Japan

  Koko Asakura

• Dept. of Biostat. & the ctr for Biostat., Harvard T.H. Chan Sc. of Pub. Health, Boston, USA

  Scott R. Evans

• Biostatistics Department, Shionogi & Co., Ltd., Osaka, Japan

  Toshimitsu Ochiai

Toshimitsu Hamasaki, Professor, National Cerebral and Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan
Koko Asakura, Research Assistant, National Cerebral and Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan
Scott Richard Evans, Senior Research Scientist, Harvard School of Public Health, 651 Huntington Avenue, Boston, Massachusetts 02115, USAToshimitsu Ochiai, Biostatistics Department, Shionogi & Co., Ltd., Japan

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