Methods and Applications of Statistics in Clinical Trials

Contributors xxiii Preface xxix 1 Absolute Risk Reduction 1 References 11 Further Reading 12 2 Accelerated Approval 14 References 25 Further Reading 26 3 AIDS Clinical Trials Group (ACTG) 27 References 37 4 Algorithm-Based Designs 40 References 51 5 Alpha-Spending Function 53 References 61 Further Reading 63 6 Application of New Designs in Phase I Trials 65 References 72 Further Reading 73 7 ASCOT Trial 74 References 78 8 Benefit/Risk Assessment in Prevention Trials 80 References 87 9 Biased Coin Randomization 90 References 104 10 Biological Assay, Overview 106 References 122 Further Reading 124 11 Block Randomization 125 References 136 Further Reading 138 12 Censored Data 139 References 141 13 Clinical Data Coordination 146 References 162 14 Clinical Data Management 164 References 169 15 Clinical Significance 170 References 185 16 Clinical Trial Misconduct 191 References 202 17 Clinical Trials, Early Cancer and Heart Disease 205 References 213 18 Cluster Randomization 216 References 228 19 Coherence in Phase I Clinical Trials 230 References 238 20 Compliance and Survival Analysis 240 References 244 21 Composite Endpoints in Clinical Trials 246 References 251 22 Confounding 252 References 261 23 Control Groups 263 References 271 24 Coronary Drug Project 273 References 282 Further Reading 284 25 Covariates 285 References 296 26 Crossover Design 300 References 308 27 Crossover Trials 310 References 317 28 Diagnostic Studies 320 References 338 Further Reading 339 29 DNA Bank 340 References 350 30 Up-and-Down and Escalation Designs 353 References 359 Further Reading 361 31 Dose Ranging Crossover Designs 362 References 379 Further Reading 382 32 Flexible Designs 383 References 396 33 Gene Therapy 399 References 411 Further Reading 422 34 Global Assessment Variables 423 References 435 35 Good Clinical Practice (GCP) 438 References 446 Further Reading 446 36 Group-Randomized Trials 448 References 462 37 Group Sequential Designs 467 References 479 38 Hazard Ratio 483 Further Reading 499 References 499 39 Large Simple Trials 500 References 506 Further Reading 508 40 Longitudinal Data 510 References 514 Further Reading 514 41 Maximum Duration and Information Trials 515 References 521 42 Missing Data 522 References 533 43 Mother to Child Human Immunodeficiency Virus Transmission Trials 536 References 545 Further Reading 549 44 Multiple Testing in Clinical Trials 550 References 556 Further Reading 557 45 Multicenter Trials 558 Readings 569 References 569 46 Multiple Endpoints 570 References 575 47 Multiple Risk Factor Intervention Trial 577 References 583 Further Reading 586 48 N-of-1 Randomized Trials 587 References 596 49 Noninferiority Trial 598 References 605 50 Nonrandomized Trials 609 References 617 51 Open-Labeled Trials 619 References 623 Further Reading 624 52 Optimizing Schedule of Administration in Phase I Clinical Trials 625 References 632 53 Partially Balanced Designs 635 References 655 54 Phase I/II Clinical Trials 658 References 665 55 Phase II/III Trials 667 References 679 Further Reading 680 56 Phase I Trials 682 References 688 57 Phase II Trials 692 References 697 Further Reading 699 58 Phase III Trials 700 References 709 59 Phase IV Trials 711 References 717 Further Reading 718 60 Phase I Trials in Oncology 719 References 723 Further Reading 724 61 Placebos 725 References 732 62 Planning a Group-Randomized Trial 736 References 743 63 Postmenopausal Estrogen/Progestin Interventions Trial (PEPI) 744 References 754 Further Reading 756 64 Preference Trials 759 References 768 Further Reading 769 65 Prevention Trials 770 References 776 66 Primary Efficacy Endpoint 779 References 786 Further Reading 788 67 Prognostic Variables in Clinical Trials 789 References 797 68 Randomization Procedures 799 References 810 69 Randomization Schedule 813 References 825 Further Reading 826 70 Repeated Measurements 827 References 838 71 Simple Randomization 841 References 849 Further Reading 849 72 Subgroups 850 References 865 73 Superiority Trials 867 References 877 Further Reading 877 74 Surrogate Endpoints 878 References 885 75 TNT Trial 887 References 892 Further Reading 893 76 UGDP Trial 894 References 914 77 Women's Health Initiative Hormone Therapy Trials 918 References 928 78 Women's Health Initiative Dietary Modification Trial 931 References 943 Index 945