1st Edition

Modern Adaptive Randomized Clinical Trials Statistical and Practical Aspects

Edited By Oleksandr Sverdlov Copyright 2016
    536 Pages 45 B/W Illustrations
    by Chapman & Hall

    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
    Oleksandr Sverdlov

    Restricted Randomization

    Efron's Biased Coin Design Revisited: Statistical Properties, Randomization-Based Inference, and Sequential Monitoring
    Victoria Plamadeala

    Adaptive Biased Coins: Achieving Better Balance without Compromising Randomness
    Alessandro Baldi Antognini and Maroussa Zagoraiou

    Brick Tunnel and Wide Brick Tunnel Randomization for Studies with Unequal Allocation
    Olga M. Kuznetsova and Yevgen Tymofyeyev

    Covariate-Adaptive Randomization

    Development of Novel Covariate-Adaptive Randomization Designs
    Wenle Zhao

    Optimal Model-Based Covariate-Adaptive Randomization Designs
    Anthony Atkinson

    Statistical Inference Following Covariate-Adaptive Randomisation: Recent Advances
    D. Stephen Coad

    Covariate-Adaptive Randomization with Unequal Allocation
    Olga M. Kuznetsova and Yevgen Tymofyeyev

    Response-Adaptive Randomization

    Optimal Allocation Designs for a Multi-Arm Multi-Objective Clinical Trial
    David Azriel

    Response-Adaptive Randomization: An Overview of Designs and Asymptotic Theory
    Li-Xin Zhang

    Statistical Inference Following Response-Adaptive Randomization
    Yanqing Yi and Xikui Wang

    Sample Size Re-Estimation in Adaptively Randomized Clinical Trials with Missing Data
    Ruitao Lin and Guosheng Yin

    Some Caveats for Outcome Adaptive Randomization in Clinical Trials
    Peter F. Thall, Patricia S. Fox, and J. Kyle Wathen

    Covariate-Adjusted Response-Adaptive Randomization

    Efficient and Ethical Adaptive Clinical Trial Designs to Detect Treatment–Covariate Interaction
    Seung Won Hyun, Tao Huang, and Hongjian Zhu

    Longitudinal Covariate-Adjusted Response-Adaptive Randomization: Impact of Missing Data
    Tao Huang and Hongjian Zhu

    Targeted Covariate-Adjusted Response-Adaptive LASSO-Based Randomized Controlled Trials
    Antoine Chambaz, Mark J. van der Laan, and Wenjing Zheng

    Covariate-Balanced Bayesian Adaptive Randomization: Achieving Tradeoff Between Inferential and Ethical Goals in Small and Moderate Size Trials
    Ying Yuan and Jing Ning

    Randomized Designs with Treatment Selection

    Multi-Arm Multi-Stage Designs for Clinical Trials with Treatment Selection
    James Wason

    Sequential Elimination in Multi-Arm Selection Trials
    Christina Yap, Xuejing Lin, and Ying Kuen K. Cheung

    Accounting for Parameter Uncertainty in Two-Stage Designs for Phase II Dose-Response Studies
    Emma McCallum and Björn Bornkamp

    Application and Practical Aspects

    A Single Pivotal Adaptive Trial in Infants with Proliferating Hemangioma: Rationale, Design Challenges, Experience, and Recommendations
    Stephane Heritier, Caroline C. Morgan-Bouniol, Serigne N. Lô, Stephanie Gautier, and Jean Jacques Voisard

    Practical Implementation of Dose–Response Adaptive Trials
    Tom Parke and Martin Kimber

    Statistical Monitoring of Data in Response-Adaptive Randomized Clinical Trials
    Paul Gallo


    Oleksandr Sverdlov

    "The discussion of the various type of adaptive designs is quite thorough and broad, incorporating many of the recent advances in the field. The book provides an excellent theoretical description of many of the more commonly employed adaptations. … a valuable resource for researchers and practitioners in adaptive trial design. The book covers a wide range of topics in adaptive randomization, going into depth in a generalized framework that applies to a broad range of trial designs, and also includes some valuable methods on how to put these trials into practice."
    Journal of Biopharmaceutical Statistics, Issue 2, 2016

    This is an impressive and useful book, which covers various types of adaptive randomisation
    designs and provides a thorough exploration of the merits of adaptive randomisation.

    —Lili Zhao, Department of Biostatistics, University of Michigan

    " . .  the book meets its objective of providing an up-to-date discussiononadaptive randomization designs and their applications in clinical trials. It is a great resource for those who are new to the field or for those who want an overview of the latest methods."

    —Stanley E. Lazic, AstraZeneca, Cambridge

    "Overall, the book covers many aspects of adaptive randomization studies and reports many new developments in the field with detailed statistical considerations. As regulatory reviewers, we can see ourselves delving into this book when we receive a submission with an adaptive randomization trial . . . The book would also prove a valuable resource for researchers in the field of adaptive randomization."

    —Xiting Yang and Gerry Gray, Food and Drug Administration

    "Many authors participated in assembling the book, including worldclass statisticians, each of whom contributed to the completeness of the disclosure of the book’s topic. The core value of the book is more than in simply demonstrated theories and formulas, but also in advice given on their practical application, specified examples, references to modern regulatory rules and links to SAS & R codes. It is a really well organised book that will be useful first and foremost for statisticians involved in clinical trials."

    International Society for Clinical Biostatistics

    " . . . the book gives a broad overview of the different adaptive randomization strategies. Due to a clear organization and well-written introduction it is convenient to read, gives fascinating insights into different options, but may also raise further questions on applicability, acceptability, and gain in efficiency, stimulating further discussion and research in this area."

    —Biometrical Journal , 2017