Clinical Trial Design Bayesian and Frequentist Adaptive Methods

There has been enormous interest and development in Bayesian adaptive designs, especially for early phases of clinical trials. However, for phase III trials, frequentist methods still play a dominant role through controlling type I and type II errors in the hypothesis testing framework. From practical perspectives, Clinical Trial Design: Bayesian and Frequentist Adaptive Methods provides comprehensive coverage of both Bayesian and frequentist approaches to all phases of clinical trial design. Before underpinning various adaptive methods, the book establishes an overview of the fundamentals of clinical trials as well as a comparison of Bayesian and frequentist statistics.

Recognizing that clinical trial design is one of the most important and useful skills in the pharmaceutical industry, this book provides detailed discussions on a variety of statistical designs, their properties, and operating characteristics for phase I, II, and III clinical trials as well as an introduction to phase IV trials. Many practical issues and challenges arising in clinical trials are addressed. Additional topics of coverage include:

• Risk and benefit analysis for toxicity and efficacy trade-offs

• Bayesian predictive probability trial monitoring

• Bayesian adaptive randomization

• Late onset toxicity and response

• Dose finding in drug combination trials

• Targeted therapy designs

The author utilizes cutting-edge clinical trial designs and statistical methods that have been employed at the world's leading medical centers as well as in the pharmaceutical industry. The software used throughout the book is freely available on the book's related website, equipping readers with the necessary tools for designing clinical trials.

Clinical Trial Design is an excellent book for courses on the topic at the graduate level. The book also serves as a valuable reference for statisticians and biostatisticians in the pharmaceutical industry as well as for researchers and practitioners who design, conduct, and monitor clinical trials in their everyday work.

1. Introduction 1

2. Fundamentals of Clinical Trials 13

3. Frequentist versus Bayesian Statistics 29

4. Phase I Trial Design 77

5. Phase II Trial Design 115

6. Phase III Trial Design 159

7. Adaptive Randomization 223

8. Late-Onset Toxicity 253

9. Drug-Combination Trials 271

10. Targeted Therapy Design 297

References 311

Author Index 329

Subject Index 333

GUOSHENG YIN, PhD, is Associate Professor in the Department of Statistics and Actuarial Science at The University of Hong Kong, and Adjunct Associate Professor in the Department of Biostatistics at The University of Texas MD Anderson Cancer Center.