Randomised Clinical Trials - Design, Practice and Reporting

Randomised Clinical Trials: Design, Practice and Reporting provides a detailed overview of the methodology for conducting clinical trials, including developing protocols, data capture, randomisation, analysis and reporting. Assuming no prior background, this user-friendly resource describes the statistical, regulatory, and practical components required for conducting randomised clinical trials. Numerous examples and case studies from industry, academia, and the research literature help readers understand each stage of the clinical trial process.
 
This second edition contains extensively revised material throughout, including new chapters covering designs for repeated measures, non-inferiority, cluster and stepped wedge trials. Other new chapters describe data and safety monitoring, biomarker studies, and feasibility studies. Updated and expanded sections discuss situations where multiple organs, different body locations or competing risks are involved, subgroup analysis, and multiple outcomes. Written by an author team with extensive experience in conducting clinical trials, this book:
* Provides comprehensive coverage of randomised clinical trials, ranging from basic to advanced
* Features several new chapters, updated case studies and examples, and references to changes in regulations
* Explains basic randomised trials, including the parallel two-group controlled trial with a single outcome measure
* Covers paired trial designs and trials with more than two interventions
* Includes a chapter on miscellaneous topics such as adaptive designs, large simple trials, Bayesian methods for very small trials, alpha-spending functions and the predictive probability test
 
Randomised Clinical Trials is essential reading for clinicians, nurses, data managers, and medical statisticians involved in clinical trials, and for health practitioners responsible for direct patient care in a clinical trial setting.

List of contents

Preface xiii
 
Part I Basic Considerations 1
 
1 Introduction 3
 
1.1 Introduction 3
 
1.2 Some completed trials 4
 
1.3 Choice of design 13
 
1.4 Practical constraints 18
 
1.5 Influencing clinical practice 20
 
1.6 History 20
 
1.7 How do trials arise? 22
 
1.8 Ethical considerations 24
 
1.9 Regulatory requirements 24
 
1.10 Focus 25
 
1.11 Further reading 25
 
2 Design Features 27
 
2.1 Introduction 27
 
2.2 The research question 29
 
2.3 Patient selection 30
 
2.4 The consent process 32
 
2.5 Choice of interventions 33
 
2.6 Choice of design 35
 
2.7 Assigning the interventions 37
 
2.8 Making the assessments 38
 
2.9 Analysis and reporting 38
 
2.10 Technical details 42
 
2.11 Guidelines 43
 
2.12 Further reading 44
 
3 The Trial Protocol 45
 
3.1 Introduction 45
 
3.2 Abstract 47
 
3.3 Background 49
 
3.4 Research objectives 49
 
3.5 Design 52
 
3.6 Intervention details 53
 
3.7 Eligibility 56
 
3.8 Randomisation 58
 
3.9 Assessment and data collection 61
 
3.10 Statistical considerations 63
 
3.11 Ethical issues 66
 
3.12 Organisational structure 69
 
3.13 Publication policy 69
 
3.14 Trial forms 70
 
3.15 Appendices 71
 
3.16 Regulatory requirements 72
 
3.17 Guidelines 74
 
3.18 Protocols 74
 
4 Measurement and Data Capture 77
 
4.1 Introduction 77
 
4.2 Types of measures 78
 
4.3 Measures and endpoints 80
 
4.4 Making the observations 91
 
4.5 Baseline measures 92
 
4.6 Data recording 93
 
4.7 Technical notes 101
 
4.8 Guidelines 101
 
5 Randomisation 103
 
5.1 Introduction 103
 
5.2 Rationale 104
 
5.3 Mechanics 104
 
5.4 Application 113
 
5.5 Carrying out randomisation 115
 
5.6 Documentation 119
 
5.7 Unacceptable methods 120
 
5.8 Guidelines 120
 
6 Trial Initiation 121
 
6.1 Introduction 121
 
6.2 Trial organisation 122
 
6.3 Data collection and processing 130
 
6.4 Internal data monitoring 132
 
6.5 Ethical and regulatory requirements 133
 
6.6 Launching the trial 134
 
6.7 Trial registries 134
 
6.8 Guidelines 135
 
7 Trial Conduct and Completion 137
 
7.1 Introduction 137
 
7.2 Regular feedback 137
 
7.3 Publicity 141
 
7.4 Protocol modifications 142
 
7.5 Preparing the publication(s) 142
 
7.6 The next trial? 145
 
7.7 Protocol 146
 
8 Basics for Analysis 147
 
8.1 Introduction 147
 
8.2 The standard Normal distribution 148
 
8.3 Confidence intervals 149
 
8.4 Statistical tests 150
 
8.5 Examples of analysis 152
 
8.6 Regression methods 169
 
8.7 Other issues 179
 
8.8 Practice 182
 
8.9 Technical details 183
 
9 Trial Size 185
 
9.1 Introduction 185
 
9.2 Significance level and power 186
 
9.3 The fundamental equation 188
 
9.4 Specific situations 190
 
9.5 Practical considerations 198
 
9.6 Further topics 203
 
9.7 Guideline 206
 
9.8 Software 206
 
10 Data and Safety Monitoring 209
 
10.1 Introduction 209
 
10.2 The DSMB 211
 
10.3 Early reviews 214
 
10.4 Interim reviews 219
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About the author

David Machin, Leicester Cancer Research Group, University of Leicester, UK; and Medical Statistics Group, School of Health and Related Research, University of Sheffield, UK.
Peter M. Fayers, Institute of Applied Health, University of Aberdeen, UK.
Bee Choo Tai, Saw Swee Hock School of Public Health, National University of Singapore, and National University Health System, Singapore; and Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore.

Summary

Randomised Clinical Trials: Design, Practice and Reporting provides a detailed overview of the methodology for conducting clinical trials, including developing protocols, data capture, randomisation, analysis and reporting. Assuming no prior background, this user-friendly resource describes the statistical, regulatory, and practical components required for conducting randomised clinical trials. Numerous examples and case studies from industry, academia, and the research literature help readers understand each stage of the clinical trial process.

This second edition contains extensively revised material throughout, including new chapters covering designs for repeated measures, non-inferiority, cluster and stepped wedge trials. Other new chapters describe data and safety monitoring, biomarker studies, and feasibility studies. Updated and expanded sections discuss situations where multiple organs, different body locations or competing risks are involved, subgroup analysis, and multiple outcomes. Written by an author team with extensive experience in conducting clinical trials, this book:
* Provides comprehensive coverage of randomised clinical trials, ranging from basic to advanced
* Features several new chapters, updated case studies and examples, and references to changes in regulations
* Explains basic randomised trials, including the parallel two-group controlled trial with a single outcome measure
* Covers paired trial designs and trials with more than two interventions
* Includes a chapter on miscellaneous topics such as adaptive designs, large simple trials, Bayesian methods for very small trials, alpha-spending functions and the predictive probability test

Randomised Clinical Trials is essential reading for clinicians, nurses, data managers, and medical statisticians involved in clinical trials, and for health practitioners responsible for direct patient care in a clinical trial setting.

Product details

• Authors: Peter Fayers, Peter M Fayers, Peter M. Fayers, Fayers Peter M., D Machin, Davi Machin, David Machin, David (Medical Research Council Cancer Tri Machin, David Fayers Machin, Bee Choo Tai, Tai Bee Choo
• Publisher: Wiley, John and Sons Ltd
• Languages: English
• Product format: Paperback / Softback
• Released: 27.05.2021
• EAN: 9781119524649
• ISBN: 978-1-119-52464-9
• No. of pages: 560
• Subjects: Natural sciences, medicine, IT, technology > Medicine > Non-clinical medicine; Medizin, Pharmacology & Pharmaceutical Medicine, Pharmakologie u. Pharmazeutische Medizin, Medical Science