Design and Analysis of Clinical Trials

DOI10.1002/0471473286MaRDI QIDQ4443478zbMATH OpenOpenAlexFDO

Publication date 13 January 2004

Published in Wiley Series in Probability and Statistics (Search for Journal in Brave)

Full work available at URL https://doi.org/10.1002/0471473286

Research exposition (monographs, survey articles) pertaining to statistics (62-02) Applications of statistics to biology and medical sciences; meta analysis (62P10)

Review text

This monograph presents on a total of 729 pages organized in 15 chapters and 2 appendices a comprehensive introduction to the methodology of clinical trials relevant for pharmaceutical drug development. The book is designed for readers with basic background in statistics. Numerous real-life examples and illustrations from clinical case studies are included to demonstrate both statistical and clinical concepts and their interactions. The Introduction provides some fundamental considerations on pharmaceutical research and current regulatory guidelines. The concepts of design and analysis of clinical trials are covered from Chapters 2 through 7. Chapter 2 introduces Basic Statistical Concepts, such as uncertainty, bias, variability, confounding, interaction, hypothesis testing, clinical significance and equivalence, and reproducibility and generalizability. In Chapter 3, the fundamental aspects for choosing design, patient and control populations of a clinical trial are addressed. Chapter 4 shows the different methods of Randomization and Blinding, which are indispensable for clinical trials. Chapter 5 discusses advantages and disadvantage of the different Designs for Clinical Trials, e.g., parallel group, crossover, titration and enrichment designs which are commonly employed at various stages of clinical development. Specific Designs for Cancer Clinical Trials are described in Chapter 6, including dose-escalation designs for phase I trials (up-and down designs and Bayesian approaches) as well as optimal and flexible multiple-stage designs for phase II cancer studies. Chapter 7 on Classification of Clinical Trials illustrates various design approaches, such as multicenter, superiority, dose-response, equivalence and noninferiority studies, combination and vaccine studies. Chapters 8 through 13 cover methodologies and various issues that are commonly encountered in the analysis of clinical data. Statistical methods for analysis are described in Chapters 8, 9, and 10, organized by type and scale of the data (continuous, categorical and censored). Group sequential procedures for interim analysis are given in Chapter 10. General requirements of sample size calculation for various types of data under different study designs are illustrated in Chapter 11. Baseline data comparisons and intent-to-treat analysis are addressed in Chapter 12 on Issues in Efficacy Evaluation. Further, multiplicity problems, such as multicenter studies, multiple comparisons, subgroup analysis and multiple endpoints are also treated. Chapter 13, on Safety Assessment, describes in a clear and illustrative way the definition for the extent of adverse events adopted by current regulatory guidelines, e.g., FDA and ICH, and considers coding, filing, reporting and statistical assessment of adverse events. Chapter 14 reviews fundamentals of Preparation and Implementation of a Clinical Protocol and quality aspects, such as monitoring, audit and inspection, are discussed. Chapter 15 on Clinical Data Management provides the regulatory requirements and their realization in the development of case report forms and the organization of the database (data entry, query, correction and validation). The volume ends with two appendices containing statistical tables and four different SAS programs for generation of random codes.

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