Methods and Applications of Statistics in Clinical Trials

N. BALAKRISHNAN, PhD, is Professor in the Department of Mathematics and Statistics at McMaster University, Canada. He is the author of over twenty books and is the coeditor of Encyclopedia of Statistical Sciences, Second Edition, also published by Wiley.

VOLUME 1 Contributors xxiii Preface xxix 1 Absolute Risk Reduction 1 2 Accelerated Approval 14 3 AIDS Clinical Trials Group (ACTG) 27 4 Algorithm-Based Designs 40 5 Alpha-Spending Function 53 6 Application of New Designs in Phase I Trials 65 7 ASCOT Trial 74 8 Benefit/Risk Assessment in Prevention Trials 80 9 Biased Coin Randomization 90 10 Biological Assay, Overview 106 11 Block Randomization 125 12 Censored Data 139 13 Clinical Data Coordination 146 14 Clinical Data Management 164 15 Clinical Significance 170 16 Clinical Trial Misconduct 191 17 Clinical Trials, Early Cancer and Heart Disease 205 18 Cluster Randomization 216 19 Coherence in Phase I Clinical Trials 230 20 Compliance and Survival Analysis 240 21 Composite Endpoints in Clinical Trials 246 22 Confounding 252 23 Control Groups 263 24 Coronary Drug Project 273 25 Covariates 285 26 Crossover Design 300 27 Crossover Trials 310 28 Diagnostic Studies 320 29 DNA Bank 340 30 Up-and-Down and Escalation Designs 353 31 Dose Ranging Crossover Designs 362 32 Flexible Designs 383 33 Gene Therapy 399 34 Global Assessment Variables 423 35 Good Clinical Practice (GCP) 438 36 Group-Randomized Trials 448 37 Group Sequential Designs 467 38 Hazard Ratio 483 39 Large Simple Trials 500 40 Longitudinal Data 510 41 Maximum Duration and Information Trials 515 42 Missing Data 522 43 Mother to Child Human Immunodeficiency Virus Transmission Trials 536 44 Multiple Testing in Clinical Trials 550 45 Multicenter Trials 558 46 Multiple Endpoints 570 47 Multiple Risk Factor Intervention Trial 577 48 N-of-1 Randomized Trials 587 49 Noninferiority Trial 598 50 Nonrandomized Trials 609 51 Open-Labeled Trials 619 52 Optimizing Schedule of Administration in Phase I Clinical Trials 625 53 Partially Balanced Designs 635 54 Phase I/II Clinical Trials 658 55 Phase II/III Trials 667 56 Phase I Trials 682 57 Phase II Trials 692 58 Phase III Trials 700 59 Phase IV Trials 711 60 Phase I Trials in Oncology 719 61 Placebos 725 62 Planning a Group-Randomized Trial 736 63 Postmenopausal Estrogen/Progestin Interventions Trial (PEPI) 744 64 Preference Trials 759 65 Prevention Trials 770 66 Primary Efficacy Endpoint 779 67 Prognostic Variables in Clinical Trials 789 68 Randomization Procedures 799 69 Randomization Schedule 813 70 Repeated Measurements 827 71 Simple Randomization 841 72 Subgroups 850 73 Superiority Trials 867 74 Surrogate Endpoints 878 75 TNT Trial 887 76 UGDP Trial 894 77 Women's Health Initiative Hormone Therapy Trials 918 78 Women's Health Initiative Dietary Modification Trial 931 Index 945 VOLUME 2 Contributors xix Preface xxiii 1 Analysis of Over- and Underdispersed Data 1 2 Analysis of Variance (ANOVA) 10 3 Assessment of Health-Related Quality of Life 26 4 Bandit Processes and Response-Adaptive Clinical Trials: The Art of Exploration Versus Exploitation 40 5 Bayesian Dose-Finding Designs in Healthy Volunteers 51 6 Bootstrap 62 7 Conditional Power in Clinical Trial Monitoring 102 8 Cost-Effectiveness Analysis 111 9 Cox-Type Proportional Hazards Models 126 10 Empirical Likelihood Methods in Clinical Experiments 146 11 Frailty Models 166 12 Futility Analysis 174 13 Imaging Science in Medicine I: Overview 187 14 Imaging Science in Medicine, II: Basics of X-Ray Imaging 213 15 Imaging Science in Medicine, III: Digital (21st Century) X-Ray Imaging 264 16 Intention-to-Treat Analysis 313 17 Interim Analyses 323 18 Interrater Reliability 334 19 Intrarater Reliability 340 20 Kaplan-Meier Plot 357 21 Logistic Regression 365 22 Metadata 380 23 Microarray 392 24 Multi-Armed Bandits, Gittins Index, and Its Calculation 416 25 Multiple Comparisons 436 26 Multiple Evaluators 446 27 Noncompartmental Analysis 457 28 Nonparametric ROC Analysis for Diagnostic Trials 483 29 Optimal Biological Dose for Molecularly Targeted Therapies 496 30 Over- and Underdispersion Models 506 31 Permutation Tests in Clinical Trials 527 32 Pharmacoepidemiology, Overview 536 33 Population Pharmacokinetic and Pharmacodynamic Methods 551 34 Proportions: Inferences and Comparisons 570 35 Publication Bias 595 36 Quality of Life 608 37 Relative Risk Modeing 622 38 Sample Size Considerations for Morbidity/Mortality Trials 633 39 Sample Size for Comparing Means 642 40 Sample Size for Comparing Proportions 653 41 Sample Size for Comparing Time-to-Event Data 664 42 Sample Size for Comparing Variabilities 672 43 Screening, Models of 689 44 Screening Trials 721 45 Secondary Efficacy End Points 731 46 Sensitivity, Specificity, and Receiver Operator Characteristic (ROC) Methods 740 47 Software for Genetics/Genomics 752 48 Stability Study Designs 778 49 Subgroup Analysis 793 50 Survival Analysis, Overview 802 51 The FDA and Regulatory Issues 815 52 The Kappa Index 836 53 Treatment Interruption 846 54 Trial Reports: Improving Reporting, Minimizing Bias, and Producing Better Evidence-Based Practice 860 55 U.S. Department of Veterans Affairs Cooperative Studies Program 876 56 Women's Health Initiative: Statistical Aspects and Selected Early Results 901 57 World Health Organization (WHO): Global Health Situation 914 Index 925