Susan S. Ellenberg, Thomas R. Fleming, David Demets

Data Monitoring Committees in Clinical Trials (eBook, PDF)

A Practical Perspective

• Format: PDF

Produktbeschreibung

-The authoritative guide for Data Monitoring Committees--fully revised and updated The number of clinical trials sponsored by government agencies and pharmaceutical companies has grown in recent years, prompting an increased need for interim monitoring of data on safety and efficacy. Data Monitoring Committees (DMCs) are an essential component of many clinical trials, safeguarding trial participants and protecting the credibility and validity of the study. Data Monitoring Committees in Clinical Trials: A Practical Perspective, 2nd Edition offers practical advice for those managing and conducting clinical trials and serving on Data Monitoring Committees, providing a practical overview of the establishment, purpose, and responsibilities of these committees. Examination of topics such as the composition and independence of DMCs, statistical, philosophical and ethical considerations, and determining when a DMC is needed, presents readers with a comprehensive foundational knowledge of clinical trial oversight. Providing recent examples to illustrate DMC principles, this fully-updated guide reflects current developments and practices in clinical trial oversight and offers expanded coverage of emerging issues and challenges in the field. This new second edition covers the most current information on DMC policies, issues in monitoring trials using new designs, and recent trial publications relevant to DMC decision-making. * Presents practical advice for those managing and conducting clinical trials and serving on Data Monitoring Committees * Illustrates the types of challenging issues Data Monitoring Committees face in practical situations * Provides updated and expanded coverage of topics including regulatory and funding agency guidelines and trial designs and their associated demands and limitations * Includes a new chapter addressing legal issues that affect DMC members and discusses general litigation concerns relevant to clinical research * Expands treatment of current journal publications addressing DMC issues Data Monitoring Committees in Clinical Trials: A Practical Perspective, 2nd Edition is a must-have text for anyone engaged in DMC activities as well as trial sponsors, clinical trial researchers, regulatory and bioethics professionals, and those associated with clinical trials in academic, government and industry settings.

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Produktdetails

• Verlag: John Wiley & Sons
• Seitenzahl: 496
• Erscheinungstermin: 14. Januar 2019
• Englisch
• ISBN-13: 9781119512646
• Artikelnr.: 55032602

Autorenporträt

SUSAN S. ELLENBERG, PHD, is Professor of Biostatistics, Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, USA. THOMAS R. FLEMING, PHD, is Professor of Biostatistics and Statistics, Department of Biostatistics, School of Public Health, University of Washington, USA. DAVID L. DEMETS, PHD, is Professor Emeritus and Founding Chair of the Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, USA.

Inhaltsangabe

Preface to the Second Edition xiii

Preface to the First Edition xv

1 Introduction 1

1.1 Motivation 1

1.2 History of data monitoring committees in government-sponsored trials 8

1.3 Data monitoring committees in trials sponsored by the pharmaceutical industry 15

1.4 Statistical methods for interim monitoring 18

1.5 When are data monitoring committees needed? 21

1.6 Models for data monitoring committees 22

1.7 Where we are today 24

1.8 Fundamental principles of data monitoring 25

References 27

2 Responsibilities of the Data Monitoring Committee and Motivating Illustrations 35

2.1 Fundamental charges 36

2.2 Specific tasks of the data monitoring committee 39

2.2.1 Initial review 40

2.2.1.1 Review of the study protocol 40

2.2.1.2 Review of procedures to ensure quality of study conduct 45

2.2.2 Evaluating the quality of ongoing study conduct 47

2.2.3 Assessing safety and efficacy data 56

2.2.3.1 Termination due to favorable benefit-to-risk 58

2.2.3.2 Termination due to unfavorable benefit-to-risk 63

2.2.3.3 Termination due to inability to answer trial questions 65

2.2.3.4 Continuation of ongoing clinical trials 68

2.2.3.5 Consideration of the overall picture: primary and secondary analyses 72

2.2.3.6 Modifying sample sizes based on ongoing assessment of event rates 76

2.2.4 Reviewing the final results 80

2.3 The data monitoring committee charter 83

References 84

3 Composition of a Data Monitoring Committee 89

3.1 Introduction 89

3.2 Required areas of expertise 90

3.3 Other relevant characteristics of committee members 96

3.4 Committee size 98

3.5 Selecting the committee chair 102

3.6 Responsibility for appointing committee members 102

3.7 Representation of other study components on the committee 104

3.8 Preparation for service on a committee 106

References 109

4 Independence of the Data Monitoring Committee: Avoiding Conflicts of Interest 113

4.1 Introduction 113

4.2 Rationale for independence 114

4.3 Financial independence 116

4.3.1 Commercial sponsors 117

4.3.2 Government sponsors 118

4.3.3 Academic investigators 118

4.4 Intellectual independence 125

4.5 Emotional conflicts 131

4.6 Best practices to address challenges to the DMC's independence 132

4.6.1 Adequate training/experience in the DMC process 133

4.6.2 Indemnification of DMC members 135

4.6.3 Maintaining confidentiality of interim data 136

4.6.4 Flexibility of procedures 138

4.6.5 DMC meeting format 139

4.6.6 Creating independent relationships and reducing conflicts of interest 141

4.6.7 Adequately informative DMC reports 142

4.7 Summary 143

References 144

5 Confidentiality Issues Relating to the Data Monitoring Committee 147

5.1 Rationale 147

5.2 Limits of confidentiality 159

5.2.1 Interim analysis reports 159

5.2.2 Access to aggregate data on efficacy and safety outcomes 161

5.2.3 Providing access to interim data on a "need-to-know" basis 164

5.2.4 Settings and procedures allowing broader unblinding of safety data 166

5.2.5 Consequences of unblinding interim data for regulatory review in ongoing trials 168

5.2.6 Some illustrations of broader unblinding 175

5.2.7 The steering committee and maintaining confidentiality 1