Studies that are unimpeachably thorough, non-political, unbiased, and properly designed… These are the standards to which everyone in clinical research aspires. Yet, the difficulties in designing trials and interpreting data are subtle and ever present. The new edition of Clinical Trials in Oncology provides a concise, nontechnical, and now thoroughly up-to-date review of methods and issues related to clinical trials. The authors emphasize the importance of proper study design, analysis, and data management and identify the major pitfalls that are seemingly inherent in these processes. This edition includes a new section that describes recent innovations in Phase I designs. Another new section on microarray data examines the challenges presented by massive data sets and describes approaches used to meet those challenges. As always, the authors use clear, lucid prose and a multitude of real-world trials as examples to convey the principles of successful trials without the need for a strong statistics or mathematics background. Although the book focuses on cancer trials, the issues and concepts are important in any clinical setting. Clinical Trials in Oncology, Second Edition works to improve the mutual understanding by clinicians and statisticians of the principles of clinical trials and helps them avoid the many hazards that can jeopardize the success of a trial.
Author(s): Stephanie Green, John Crowley, Jacqueline Benedetti
Edition: 2nd
Publisher: Chapman and Hall CRC
Year: 2003
Language: English
Pages: 280
Interdisciplinary Statistics CLINICAL TRIALS in ONCOLOGY, Second Edition......Page 2
Acknowlegdments......Page 29
Contents......Page 24
Contents......Page 0
1.1 A brief history of clinical trials......Page 30
1.2 The Southwest Oncology Group......Page 35
1.3 Example trials......Page 36
1.4 The reason for this book......Page 38
2.1 Introduction......Page 39
2.2 The Phase II trial — estimation......Page 47
2.3 The Phase III trial – hypothesis testing......Page 51
2.3.1 Response as the outcome......Page 52
2.3.2 Survival as the outcome......Page 58
2.4 The proportional hazards model......Page 65
2.5 Sample size calculations......Page 67
2.6 Concluding remarks......Page 68
3.1 Introduction......Page 69
RYRY3 Uligibility treatments endpoints......Page 70
RYRYM Assumptions for sample size calculation......Page 71
RYRYR Traditional designs......Page 76
RYRY3 Newer Phase I designs......Page 77
RYRY: Eonsiderations for biologic agents......Page 80
3.4 Phase II trials......Page 81
RY:YR The Standard Southwest Oncology roup Phase II design......Page 82
activityY......Page 84
not......Page 86
pilot studiesj......Page 89
StratiYcation factors......Page 90
Randomization schemes......Page 91
adaptive allocation......Page 92
intent to treat principle......Page 93
randomized consent designs......Page 94
Placebo’controlled......Page 95
RYMY3 Two’arm trials......Page 97
prove......Page 98
proportional hazards assumptionY......Page 99
Multiple endpoints......Page 100
proving......Page 101
3.6 Conclusion......Page 104
4.1 Introduction......Page 106
4.2 Types of multi-arm trials......Page 107
4.3 Significance level......Page 110
4.4 Power......Page 111
5.1 Planned interim analyses......Page 123
5.2 Data monitoring committees: Rationale and responsibilities......Page 129
5.3 Monitoring committees: Composition......Page 133
5.4 Examples......Page 138
5.5 Concluding remarks......Page 148
6.1 Introduction: Why worry?......Page 149
6.2 Protocol development......Page 154
6.3 Data collection......Page 162
6.4 Protocol management and evaluation......Page 169
6.5 Quality assurance audits......Page 175
6.6 Training......Page 176
6.7 Data base management......Page 177
6.8 Conclusion......Page 180
6.9 Appendix: Examples......Page 181
CHAPTER 7: Reporting of Results......Page 190
7.1 Timing of report......Page 191
7.2 Required information......Page 193
7.3 Analyses......Page 195
7.4 Conclusion......Page 204
8.2 Historical controls......Page 205
8.3 Competing risks......Page 212
8.4 Outcome by outcome analyses......Page 219
8.5 Subset analyses......Page 227
8.6 Surrogate endpoints......Page 230
9.1 Introduction......Page 233
9.2 Some background and notation......Page 234
9.3 Identification of prognostic factors......Page 236
9.4 Forming prognostic groups......Page 243
9.5 Analysis of microarray data......Page 248
9.6 Meta-Analysis......Page 250
9.7 Concluding remarks......Page 256
CHAPTER 10: Summary and Conclusions......Page 257
Bibliography......Page 4
