Methods and Applications of Statistics in Clinical Trials

Volume 1: Concepts, Principles, Trials, and Designs

Balakrishnan, Narayanaswamy (Editor)

Methods and Applications of Statistics

1. Edition March 2014
992 Pages, Hardcover
Wiley & Sons Ltd

ISBN: 978-1-118-30473-0

John Wiley & Sons

Wiley Online Library Sample Chapter

Short Description

This comprehensive book features both new and established material on the key statistical principles and concepts for designing modern-day clinical trials, such as hazard ratio, flexible designs, confounding, covariates, missing data, and longitudinal data. It discusses the various kinds of trials that can be found in today's clinical setting including open-labeled trials, multicentered trials, and superiority trials. It also explores such ongoing, cutting-edge trials as early cancer & heart disease, mother to child human immunodeficiency virus transmission, women's health initiative dietary, and AIDS.

Further versions

A complete guide to the key statistical concepts essential for the design and construction of clinical trials

As the newest major resource in the field of medical research, Methods and Applications of Statistics in Clinical Trials, Volume 1: Concepts, Principles, Trials, and Designs presents a timely and authoritative reviewof the central statistical concepts used to build clinical trials that obtain the best results. The referenceunveils modern approaches vital to understanding, creating, and evaluating data obtained throughoutthe various stages of clinical trial design and analysis.

Accessible and comprehensive, the first volume in a two-part set includes newly-written articles as well as established literature from the Wiley Encyclopedia of Clinical Trials. Illustrating a variety of statistical concepts and principles such as longitudinal data, missing data, covariates, biased-coin randomization, repeated measurements, and simple randomization, the book also provides in-depth coverage of the various trial designs found within phase I-IV trials. Methods and Applications of Statistics in Clinical Trials, Volume 1: Concepts, Principles, Trials, and Designs also features:
* Detailed chapters on the type of trial designs, such as adaptive, crossover, group-randomized, multicenter, non-inferiority, non-randomized, open-labeled, preference, prevention, and superiority trials
* Over 100 contributions from leading academics, researchers, and practitioners
* An exploration of ongoing, cutting-edge clinical trials on early cancer and heart disease, mother-to-child human immunodeficiency virus transmission trials, and the AIDS Clinical Trials Group

Methods and Applications of Statistics in Clinical Trials, Volume 1: Concepts, Principles, Trials, and Designs is an excellent reference for researchers, practitioners, and students in the fields of clinicaltrials, pharmaceutics, biostatistics, medical research design, biology, biomedicine, epidemiology,and public health.

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

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.

N. Balakrishnan, McMaster University, Hamilton, Canada