Group-Sequential Clinical Trials with Multiple Co-Objectives

Front Cover
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.
 

What people are saying - Write a review

We haven't found any reviews in the usual places.

Contents

1 Introduction
1
2 Interim Evaluation of Efficacy in Clinical Trials with Two Coprimary Endpoints
15
3 Sample Size Recalculation in Clinical Trials with Two Coprimary Endpoints
41
4 Interim Evaluation of Efficacy or Futility in Clinical Trials with Two Coprimary Endpoints
50
5 Interim Evaluation of Efficacy in Clinical Trials with Two Primary Endpoints
67
6 GroupSequential ThreeArm Noninferiority Clinical Trials
81
7 Future Developments
96
Appendix ACalculation of Power and ConditionalPower in GroupSequential Clinical Trialswith Two Coprimary Endpoints
103
Appendix BEfficacy and Futility Critical Boundariesand Sample Size Calculationin GroupSequential Clinical Trialswith Two Coprimary Endpoints
107
Appendix CASN Calculations in GroupSequentialClinical Trials Including Efficacyand Futility Assessments
109
Appendix DASN Calculations in ThreeArmGroupSequential Clinical Trials
111
Copyright

Other editions - View all

Common terms and phrases

About the author (2016)

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