The Theory of Response-Adaptive Randomization in Clinical Trials

Presents a firm mathematical basis for the use of response-adaptive randomization procedures in practice

The Theory of Response-Adaptive Randomization in Clinical Trials is the result of the authors' ten-year collaboration as well as their collaborations with other researchers in investigating the important questions regarding response-adaptive randomization in a rigorous mathematical framework. Response-adaptive allocation has a long history in biostatistics literature; however, largely due to the disastrous ECMO trial in the early 1980s, there is a general reluctance to use these procedures.

This timely book represents a mathematically rigorous subdiscipline of experimental design involving randomization and answers fundamental questions, including:

• How does response-adaptive randomization affect power?
• Can standard inferential tests be applied following response-adaptive randomization?
• What is the effect of delayed response?
• Which procedure is most appropriate and how can "most appropriate" be quantified?
• How can heterogeneity of the patient population be incorporated?
• Can response-adaptive randomization be performed with more than two treatments or with continuous responses?

The answers to these questions communicate a thorough understanding of the asymptotic properties of each procedure discussed, including asymptotic normality, consistency, and asymptotic variance of the induced allocation. Topical coverage includes:

• The relationship between power and response-adaptive randomization
• The general result for determining asymptotically best procedures
• Procedures based on urn models
• Procedures based on sequential estimation
• Implications for the practice of clinical trials

Useful for graduate students in mathematics, statistics, and biostatistics as well as researchers and industrial and academic biostatisticians, this book offers a rigorous treatment of the subject in order to find the optimal procedure to use in practice.