Modern Adaptive Randomized Clinical Trials Statistical and Practical Aspects Chapman & Hall/CRC Biostatistics Series

Is adaptive randomization always better than traditional fixed-schedule randomization? Which procedures should be used and under which circumstances? What special considerations are required for adaptive randomized trials? What kind of statistical inference should be used to achieve valid and unbiased treatment comparisons following adaptive randomization designs?

Modern Adaptive Randomized Clinical Trials: Statistical and Practical Aspects answers these questions and more.

From novel designs to cutting-edge applications, this book presents several new and key developments in adaptive randomization. It also offers a fresh and critical look at a number of already-classical topics.

Featuring contributions from statisticians, clinical trialists, and subject-matter experts in academia and the pharmaceutical industry, the text:

• Clarifies the taxonomy of the concept of adaptive randomization
• Discusses restricted, covariate-adaptive, response-adaptive, and covariate-adjusted response-adaptive (CARA) randomization designs, as well as randomized designs with treatment selection
• Gives an exposition to many novel adaptive randomization techniques such as brick tunnel randomization, targeted least absolute shrinkage and selection operator (LASSO)-based CARA randomization, multi-arm multi-stage (MAMS) designs, to name a few
• Addresses the issues of statistical inference following covariate-adaptive and response-adaptive randomization designs
• Describes a successful implementation of a single pivotal phase II/III adaptive trial in infants with proliferating hemangioma
• Explores some practical aspects of phase II dose-ranging studies and examines statistical monitoring and interim analysis issues in response-adaptive randomized clinical trials

Modern Adaptive Randomized Clinical Trials: Statistical and Practical Aspects covers a wide spectrum of topics related to adaptive randomization designs in contemporary clinical trials. The book provides a thorough exploration of the merits of adaptive randomization and aids in identifying when it is appropriate to apply such designs in practice.

An Overview of Adaptive Randomization Designs in Clinical Trials. Efron's Biased Coin Design Revisited: Statistical Properties, Randomization-Based Inference, and Sequential Monitoring. Adaptive Biased Coins: Achieving Better Balance without Compromising Randomness. Brick Tunnel and Wide Brick Tunnel Randomization for Studies with Unequal Allocation. Development of Novel Covariate-Adaptive Randomization Designs. Optimal Model-Based Covariate-Adaptive Randomization Designs. Statistical Inference Following Covariate-Adaptive Randomisation: Recent Advances. Covariate-Adaptive Randomization with Unequal Allocation. Optimal Allocation Designs for a Multi-Arm Multi-Objective Clinical Trial. Response-Adaptive Randomization: An Overview of Designs and Asymptotic Theory. Statistical Inference Following Response-Adaptive Randomization. Sample Size Re-Estimation in Adaptively Randomized Clinical Trials with Missing Data. Some Caveats for Outcome Adaptive Randomization in Clinical Trials. Efficient and Ethical Adaptive Clinical Trial Designs to Detect Treatment–Covariate Interaction. Longitudinal Covariate-Adjusted Response-Adaptive Randomization: Impact of Missing Data. Targeted Covariate-Adjusted Response-Adaptive LASSO-Based Randomized Controlled Trials. Covariate-Balanced Bayesian Adaptive Randomization: Achieving Tradeoff Between Inferential and Ethical Goals in Small and Moderate Size Trials. Multi-Arm Multi-Stage Designs for Clinical Trials with Treatment Selection. Sequential Elimination in Multi-Arm Selection Trials. Accounting for Parameter Uncertainty in Two-Stage Designs for Phase II Dose-Response Studies. A Single Pivotal Adaptive Trial in Infants with Proliferating Hemangioma: Rationale, Design Challenges, Experience, and Recommendations. Practical Implementation of Dose–Response Adaptive Trials. Statistical Monitoring of Data in Response-Adaptive Randomized Clinical Trials.