Shein-Chung Chow, Jen-Pei Liu

Design and Analysis of Clinical Trials (eBook, PDF)

Concepts and Methodologies

• Format: PDF

Produktbeschreibung

Praise for the Second Edition: "...a grand feast for biostatisticians. It stands ready to satisfy the appetite of any pharmaceutical scientist with a respectable statistical appetite." --Journal of Clinical Research Best Practices The Third Edition of Design and Analysis of Clinical Trials provides complete, comprehensive, and expanded coverage of recent health treatments and interventions. Featuring a unified presentation, the book provides a well-balanced summary of current regulatory requirements and recently developed statistical methods as well as an overview of the various designs and analyses that are utilized at different stages of clinical research and development. Additional features of this Third Edition include: * New chapters on biomarker development and target clinical trials, adaptive design, trials for evaluating diagnostic devices, statistical methods for translational medicine, and traditional Chinese medicine * A balanced overview of current and emerging clinical issues as well as newly developed statistical methodologies * Practical examples of clinical trials that demonstrate everyday applicability, with illustrations and examples to explain key concepts * New sections on bridging studies and global trials, QT studies, multinational trials, comparative effectiveness trials, and the analysis of QT/QTc prolongation * A complete and balanced presentation of clinical and scientific issues, statistical concepts, and methodologies for bridging clinical and statistical disciplines * An update of each chapter that reflects changes in regulatory requirements for the drug review and approval process and recent developments in statistical design and methodology for clinical research and development Design and Analysis of Clinical Trials, Third Edition continues to be an ideal clinical research reference for academic, pharmaceutical, medical, and regulatory scientists/researchers, statisticians, and graduate-level students.

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Produktdetails

• Verlag: John Wiley & Sons
• Seitenzahl: 892
• Erscheinungstermin: 6. November 2013
• Englisch
• ISBN-13: 9781118458136
• Artikelnr.: 39940983

Autorenporträt

SHEIN-CHUNG CHOW, PhD, is Professor in the Department of Biostatistics and Bioinformatics at Duke University School of Medicine. JEN-PEI LIU, PhD, is Professor in the Department of Agronomy and Institute of Epidemiology and Preventive Medicine at the National Taiwan University. He has authored multiple articles and books on clinical trials and been involved in clinical trials as a biostatistician for more than twenty-five years.

Inhaltsangabe

Preface xi PART I PRELIMINARIES 1 Introduction 3 1.1 What are Clinical Trials?
3 1.2 History of Clinical Trials
4 1.3 Regulatory Process and Requirements
10 1.4 Investigational New Drug Application
17 1.5 New Drug Application
24 1.6 Clinical Development and Practice
31 1.7 AIMS and Structure of the Book
42 2 Basic Statistical Concepts 45 2.1 Introduction
45 2.2 Uncertainty and Probability
46 2.3 Bias and Variability
49 2.4 Confounding and Interaction
57 2.5 Descriptive and Inferential Statistics
66 2.6 Hypotheses Testing and p-Values
68 2.7 Clinical Significance and Clinical Equivalence
75 2.8 Reproducibility and Generalizability
79 3 Basic Design Considerations 85 3.1 Introduction
85 3.2 Goals of Clinical Trials
86 3.3 Target Population and Patient Selection
90 3.4 Selection of Controls
97 3.5 Statistical Considerations
105 3.6 Other Issues
112 3.7 Discussion
115 4 Randomization and Blinding 117 4.1 Introduction
117 4.2 Randomization Models
118 4.3 Randomization Methods
124 4.4 Implementation of Randomization
144 4.5 Generalization of Controlled Randomized Trials
149 4.6 Blinding
153 4.7 Discussion
160 PART II DESIGNS AND THEIR CLASSIFICATIONS 5 Designs for Clinical Trials 165 5.1 Introduction
165 5.2 Parallel Group Designs
167 5.3 Clustered Randomized Designs
172 5.4 Crossover Designs
177 5.5 Titration Designs
185 5.6 Enrichment Designs
191 5.7 Group Sequential Designs
195 5.8 Placebo-Challenging Designs
197 5.9 Blinded Reader Designs
203 5.10 Discussion
207 6 Designs for Cancer Clinical Trials 211 6.1 Introduction
211 6.2 General Considerations for Phase I Cancer Clinical Trials
213 6.3 Single-Stage Up-and-Down Phase I Designs
214 6.4 Two-Stage Up-and-Down Phase I Designs
217 6.5 Continual Reassessment Method Phase I Designs
219 6.6 Optimal and Flexible Multiple-Stage Designs
222 6.7 Randomized Phase II Designs
229 6.8 Discussion
232 7 Classification of Clinical Trials 237 7.1 Introduction
237 7.2 Multicenter Trials
238 7.3 Superiority Trials
245 7.4 Active Control and Equivalence/Noninferiority Trials
248 7.5 Dose-Response Trials
261 7.6 Combination Trials
266 7.7 Bridging Studies and Global Trials
278 7.8 Vaccine Clinical Trials
285 7.9 QT Studies
291 7.10 Discussion
299 PART III ANALYSIS OF CLINICAL DATA 8 Analysis of Continuous Data 305 8.1 Introduction
305 8.2 Estimation
306 8.3 Test Statistics
310 8.4 Analysis of Variance
316 8.5 Analysis of Covariance
323 8.6 Nonparametric Methods
325 8.7 Repeated Measures
332 8.8 Discussion
341 9 Analysis of Categorical Data 343 9.1 Introduction
343 9.2 Statistical Inference for One Sample
345 9.3 Inference of Independent Samples
358 9.4 Ordered Categorical Data
364 9.5 Combining Categorical Data
368 9.6 Model-Based Methods
374 9.7 Repeated Categorical Data
382 9.8 Discussion
387 10 Censored Data and Interim Analysis 389 10.1 Introduction
389 10.2 Estimation of the Survival Function
391 10.3 Comparison Between Survival Functions
399 10.4 Cox's Proportional Hazard Model
405 10.5 Calendar Time and Information Time
419 10.6 Group Sequential Methods
424 10.7 Discussion
438 11 Sample Size Determination 441 11.1 Introduction
441 11.2 Basic Concept
442 11.3 Two Samples
447 11.4 Multiple Samples
456 11.5 Censored Data
459 11.6 Dose-Response Studies
464 11.7 Crossover Designs
471 11.8 Equivalence and Noninferiority Trials
481 11.9 Multiple-Stage Design in Cancer Trials
490 11.10 Multinational Trials
490 11.11 Comparing Variabilities
500 11.12 Discussion
517 PART IV ISSUES IN EVALUATION 12 Issues in Efficacy Evaluation 521 12.1 Introduction
521 12.2 Baseline Comparison
523 12.3 Intention-to-Treat Principle and Efficacy Analysis
528 12.4 Adjustment for Covariates
536 12.5 Multicenter Trials
541 12.6 Multiplicity
548 12.7 Data Monitoring
558 12.8 Use of Genetic Information for Evaluation of Efficacy
564 12.9 Sample Size Reestimation
570 12.10 Discussion
572 13 Safety Assessment 573 13.1 Introduction
573 13.2 Extent of Exposure
574 13.3 Coding of Adverse Events
582 13.4 Analysis of Adverse Events
595 13.5 Analysis of Laboratory Data
602 13.6 Analysis of QT/QTc Prolongation
610 13.7 Discussion
615 PART V RECENT DEVELOPMENT 14 Biomarkers and Targeted Clinical Trials 619 14.1 Introduction
619 14.2 Concepts and Strategies
620 14.3 Biomarker Development and Validation
623 14.4 Designs of Targeted Clinical Trials
630 14.5 Analyses of Targeted Clinical Trials
640 14.6 Discussion
647 15 Trials for Evaluating Accuracy of Diagnostic Devices 649 15.1 Introduction
649 15.2 Study Design
651 15.3 Measures of Diagnostic Accuracy
656 15.4 Reporting Results
663 15.5 Sample Size Estimation
672 15.6 Discussion
675 16 Statistical Methods in Translational Medicine 677 16.1 Introduction
677 16.2 Biomarker Development
678 16.3 Bench-to-Bedside
682 16.4 Animal Model Versus Human Model
689 16.5 Translation in Study Endpoints
691 16.6 Bridging Studies
696 16.7 Discussion
699 16.8 Appendix
700 17 Adaptive Clinical Trial Designs 703 17.1 Introduction
703 17.2 What Is Adaptive Design?
704 17.3 Well-Understood and Less Well-Understood Designs
709 17.4 Clinical/Statistical and Regulatory Perspectives
713 17.5 Impact of Protocol Amendments
716 17.6 Challenges in By-Design Adaptations
721 17.7 Obstacles of Retrospective Adaptations
727 17.8 Discussion
729 18 Traditional Chinese Medicine 733 18.1 Introduction
733 18.2 Fundamental Differences
734 18.3 Basic Considerations of TCM Clinical Trials
741 18.4 Other Issues in TCM Research and Development
744 18.5 Consortium for Globalization of Traditional Chinese Medicine
751 18.6 Discussion
752 PART VI CONDUCT OF CLINICAL TRIALS 19 Preparation and Implementation of a Clinical Protocol 755 19.1 Introduction
755 19.2 Structure and Components of a Protocol
756 19.3 Points to be Considered and Common Pitfalls During Development and Preparation of a Protocol
762 19.4 Common Departures for Implementation of a Protocol
765 19.5 Monitoring
Audit
and Inspection
771 19.6 Quality Assessment of a Clinical Trial
775 19.7 Discussion
777 20 Data Management of a Clinical Trial 779 20.1 Introduction
779 20.2 Regulatory Requirements
781 20.3 Development of Case Report Forms
783 20.4 Database Development
787 20.5 Data Entry
Query
and Correction
788 20.6 Data Validation and Quality
791 20.7 Database Lock
Archive
and Transfer
792 20.8 Critical Issues
795 References 799 Appendix A 845 Index 851

Rezensionen

"In summary, this third edition is an impressive expansion beyond a remarkable second edition. This book would be good reference for biostatisticians, clinical researchers, and pharmaceutical scientists in clinical research and development." (Journal of Biopharmaceutical Statistics, 1 July 2014)