Clinical trials in oncology / Stephanie Green, Jacqueline Benedetti, John Crowley.

Format:

Book

Author/Creator:

Green, Stephanie (Stephanie Janet)

Contributor:

Benedetti, Jacqueline.

Crowley, John, 1946-

Series:

Interdisciplinary statistics

Chapman & Hall/CRC interdisciplinary statistics series

Language:

English

Subjects (All):

Cancer--Research--Statistical methods.

Cancer--Research.

Cancer.

Clinical trials.

Clinical Trials as Topic--standards.

Neoplasms--therapy.

Clinical Trials as Topic.

Data Interpretation, Statistical.

Medical Subjects:

Clinical Trials as Topic--standards.

Neoplasms--therapy.

Clinical Trials as Topic.

Data Interpretation, Statistical.

Physical Description:

xi, 265 pages : illustrations ; 25 cm.

Edition:

Second edition.

Place of Publication:

Boca Raton, Fla. : Chapman & Hall/CRC, [2003]

Summary:

Provides a concise, up-to-date review of methods and issues related to clinical trials. Emphasizes proper study design, analysis, and data management and identifies common problems. Expanded-outline format.

Contents:

1.1 A brief history of clinical trials 1

1.2 The Southwest Oncology Group 6

1.3 Example trials 7

2 Statistical Concepts 11

2.2 The Phase II trial

estimation 19

2.3 The Phase III trial - hypothesis testing 23

2.3.1 Response as the outcome 24

2.3.2 Survival as the outcome 30

2.4 The proportional hazards model 37

2.5 Sample size calculations 39

3 The Design of Clinical Trials 41

3.1.2 Eligibility, treatments, endpoints 42

3.1.3 Differences to be detected or precision of estimates 43

3.1.4 Method of treatment assignment 43

3.1.5 Assumptions for sample size calculation 43

3.2 Endpoints 44

3.3 Phase I trials 48

3.3.1 Traditional designs 48

3.3.2 Newer Phase I designs 49

3.3.3 Phase I/II designs 52

3.3.4 Considerations for biologic agents 52

3.4 Phase II trials 53

3.4.1 The Standard Southwest Oncology Group Phase II design 54

3.4.2 Randomized Phase II designs 58

3.4.3 Other Phase II designs 61

3.5 Phase III trials 62

3.5.1 Randomization 62

3.5.2 Two-arm trials 69

3.5.3 Equivalence or noninferiority trials 73

4 Multi-Arm Trials 79

4.2 Types of multi-arm trials 80

4.3 Significance level 83

4.4 Power 84

4.5 Interaction 86

4.6 Other model assumptions 90

4.7 To screen or not to screen 90

4.8 Timing of randomization 92

5 Interim Analysis and Data Monitoring Committees 97

5.1 Planned interim analyses 97

5.2 Data monitoring committees: Rationale and responsibilities 103

5.3 Monitoring committees: Composition 107

5.4.1 Stopping early for positive results 112

5.4.2 Stopping early for negative results 115

5.4.3 Stopping an equivalence trial early for positive results 115

5.4.4 Stopping based on toxicity and lack of compliance 118

5.4.5 Emergency stopping based on unexpected toxic deaths 121

6 Data Management and Quality Control 123

6.1 Introduction: Why worry? 123

6.2 Protocol development 128

6.2.3 Drug information 129

6.2.4 Stage definitions 129

6.2.5 Eligibility criteria 129

6.2.6 Stratification factors and subsets 130

6.2.7 Treatment plan 131

6.2.8 Treatment modification 131

6.2.9 Study calendar 132

6.2.10 Endpoint definitions 132

6.2.11 Statistical considerations 133

6.2.12 Discipline review 133

6.2.13 Registration instructions 134

6.2.14 Data submission instructions 134

6.2.15 Special instructions 135

6.2.16 Regulatory requirements 135

6.2.18 Forms 135

6.2.20 Additional comments on SWOG study 8811 136

6.3 Data collection 136

6.3.1 Basic data items 137

6.3.2 Data forms 140

6.4 Protocol management and evaluation 143

6.4.1 Registration 143

6.4.2 Data flow 144

6.4.3 Evaluation of data 145

6.4.4 Publication 148

6.4.5 Resolution of problems: Examples from SWOG 8811 148

6.5 Quality assurance audits 149

6.6 Training 150

6.7 Data base management 151

6.7.1 Data base structures 151

6.7.2 Data collection, transmission, and entry 152

6.9.1 Treatment table for 8811 155

6.9.2 Sample study calendar 155

6.9.3 Sample flow sheet 156

6.9.4 Sample treatment and toxicity form for a single agent treatment given every 4 weeks for 1 day 157

6.9.5 Sample follow-up form 158

6.9.6 Sample notice of death 159

6.9.7 Sample checklist 160

6.9.8 Sample tables 162

7 Reporting of Results 165

7.1 Timing of report 166

7.1.1 Phase II trials 167

7.1.2 Phase III trials 167

7.2 Required information 168

7.2.1 Objectives and design 168

7.2.2 Eligibility and treatment 168

7.2.3 Results 169

7.3 Analyses 170

7.3.1 Exclusions, intent to treat 170

7.3.2 Summary statistics: Estimates and variability of estimates 172

7.3.3 Interpretation of results 175

7.3.4 Secondary analyses 178

8 Pitfalls 181

8.2 Historical controls 181

8.3 Competing risks 188

8.4 Outcome by outcome analyses 195

8.4.1 Survival by response comparisons 195

8.4.2 Dose intensity analyses 199

8.5 Subset analyses 203

8.6 Surrogate endpoints 206

9 Exploratory Analyses 209

9.2 Some background and notation 210

9.3 Identification of prognostic factors 212

9.3.1 Scale of measurement 213

9.3.2 Choice of model 216

9.4 Forming prognostic groups 219

9.5 Analysis of microarray data 224

9.6 Meta-Analysis 226

9.6.1 Some principles of meta-analysis 227

9.6.2 An example meta-analysis: Portal vein infusion 228

9.6.3 Conclusions from the portal vein meta-analysis 231

9.6.4 Some final remarks on meta-analysis 231.

Notes:

Includes bibliographical references (pages [237]-252) and index.

ISBN:

1584883022

OCLC:

49376206