Randomized Clinical Trials Design, Practice and Reporting

by Machin, David; Fayers, Peter M.

• ISBN13: 9780471498124
• ISBN10: 0471498122
• Edition: 1st
• Format: Paperback
• Copyright: 2010-03-22
• Publisher: Wiley

Summary

Using examples and case studies from industry, academia and research literature, Randomized Clinical Trials provides a detailed overview of the key issues involved in designing, conducting, analyzing and reporting randomized clinical trails. It examines the methodology for conducting Phase III clinical trials, developing the protocols, the practice for capturing, measuring and analyzing the resulting clinical data and their subsequent reporting.

Author Biography

David Machin, Medical Statistics Group, School of Health and Related Sciences, University of Sheffield, UK and Children's Cancer and Leukaemia Group, University of Leicester,  UK

Peter M Fayers, Department of Public Health, University of Aberdeen, UK and Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway

Table of Contents

Preface	p. xi
Introduction	p. 1
Introduction	p. 1
Some completed trials	p. 2
Choice of design	p. 9
Practical constraints	p. 14
Influencing clinical practice	p. 15
History	p. 16
How trials arise	p. 18
Ethical considerations	p. 19
Regulatory requirements	p. 20
Focus	p. 20
Further reading	p. 21
Design Features	p. 23
Introduction	p. 23
The research question	p. 24
Patient selection	p. 26
The consent process	p. 28
Choice of interventions	p. 29
Choice of design	p. 31
Assigning the interventions	p. 33
Making the assessments	p. 34
Analysis and reporting	p. 34
Technical details	p. 37
Guidelines	p. 38
Further reading	p. 39
The Trial Protocol	p. 41
Introduction	p. 41
Protocol - abstract	p. 43
Protocol - background	p. 44
Protocol - research objectives	p. 45
Protocol - design	p. 48
Protocol - intervention details	p. 49
Protocol - eligibility	p. 52
Protocol - randomization	p. 53
Protocol - assessment and data collection	p. 56
Protocol - statistical considerations	p. 58
Protocol - ethical issues	p. 62
Protocol - organizational structure	p. 64
Protocol - publication policy	p. 65
Protocol - trial forms	p. 66
Protocol - appendices	p. 67
Regulatory requirements	p. 68
Guidelines	p. 69
Protocols	p. 69
Measurement and Data Capture	p. 71
Introduction	p. 71
Measures and endpoints	p. 72
Making the observations	p. 79
Baseline measures	p. 82
Types of measures	p. 82
Data recording	p. 84
Technical notes	p. 92
Guidelines	p. 93
Randomization	p. 95
Introduction	p. 95
Rationale	p. 96
Mechanics	p. 96
Application	p. 105
Carrying out randomization	p. 106
Documentation	p. 109
Unacceptable methods	p. 110
Software	p. 110
Guidelines	p. 111
Trial Initiation	p. 113
Introduction	p. 113
Trial organization	p. 114
Data collection and processing	p. 121
Data monitoring	p. 124
Ethical and regulatory requirements	p. 127
Launching the trial	p. 127
Trial registries	p. 128
Guidelines	p. 128
Trial Conduct	p. 131
Introduction	p. 131
Regular feedback	p. 131
Publicity	p. 134
Data monitoring committees	p. 135
Protocol modifications	p. 139
Preparing the publication(s)	p. 140
The next trial?	p. 143
Protocols	p. 143
Basics of Analysis	p. 145
Introduction	p. 145
Confidence intervals	p. 146
Statistical tests	p. 147
Examples of analysis	p. 148
Other issues	p. 171
Practice	p. 175
Technical details	p. 175
Trial Size	p. 179
Introduction	p. 179
Significance level and power	p. 180
The fundamental equation	p. 182
Specific situations	p. 184
Practical considerations	p. 190
Further topics	p. 194
Other methods and software	p. 196
Guideline	p. 197
Reporting	p. 199
Introduction	p. 199
Publication guidelines	p. 200
Responsibilities	p. 204
Background	p. 206
Methods	p. 206
Findings	p. 217
When things go wrong	p. 226
Conclusions	p. 227
Guidelines	p. 227
Adaptations of the Basic Design	p. 229
Introduction	p. 229
Repeated measures	p. 230
Cluster-randomized trials	p. 236
Non-inferiority trials	p. 244
Guidelines	p. 249
Paired Designs	p. 251
Cross-over trials	p. 251
Split-mouth designs	p. 264
Paired organs	p. 269
More Than Two Interventions	p. 275
Introduction	p. 275
Unstructured comparisons	p. 275
Comparisons with placebo (or standard)	p. 279
Dose response designs	p. 284
Factorial trials	p. 289
Further Topics	p. 297
Introduction	p. 297
Adaptive approaches	p. 298
Large simple trials	p. 306
Bayesian methods	p. 310
Zelen randomized-consent designs	p. 315
Systematic overviews	p. 318
Conclusion	p. 322
Statistical Tables	p. 323
Glossary	p. 329
References	p. 337
Index	p. 349
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