The Theory of Response-Adaptive Randomization in Clinical Trials

A unique overview that melds the concepts of conditional probability and stochastic processes into real-life applications The role of randomization techniques in clinical trials has become increasingly important. This comprehensive guide combines both the applied aspects of randomization in clinical trials with a probabilistic treatment of properties of randomization. Taking an unabashedly non-Bayesian and nonparametric approach to inference, the book focuses on the linear rank test under a randomization model, with added discussion on likelihood-based inference as it relates to sufficiency and ancillarity. Developments in stochastic processes and applied probability are also given where appropriate. Intuition is stressed over mathematics, but not without a clear development of the latter in the context of the former. Providing a consolidated review of the field, the book includes relevant and practical discussions of: * The benefits of randomization in terms of reduction of bias * Randomization as a basis for inference * Covariate-adaptive and response-adaptive randomization * Current philosophies, controversies, and new developments With ample problem sets, theoretical exercises, and short computer simulations using SAS, Randomization in Clinical Trials: Theory and Practice is equally useful as a standard textbook in biostatistics graduate programs as well as a reliable reference for biostatisticians in practice.

A valuable new edition of the trusted, practical guide to managing data in clinical trials Regardless of size, type, or complexity, accurate results for any clinical trial are ultimately determined by the quality of the collected data. Management of Data in Clinical Trials, Second Edition explores data management and trial organization as the keys to developing an accurate and reliable clinical trial. With a focus on the traditional aspects of data collection as well as recent advances in technology, this new edition provides a complete and accessible guide to the management structure of a clinical trial, from planning and development to design and analysis. Practical approaches that result in the collection of complete and timely data are also provided. While maintaining a comprehensive overview of the knowledge and tools that are essential for the organization of a modern clinical trial, the author has expanded the topical coverage in the Second Edition to reflect the possible uses of recent advances in technology in the data collection process. In addition, the Second Edition discusses the impact of international regulations governing the conduct of clinical trials and provides guidelines on ensuring compliance with national requirements. Newly featured topics include: The growing availability of «off-the-shelf» solutions for clinical trials Potential models for collaboration in the conduct of clinical trials between academia and the pharmaceutical industry The increasing use of the Internet in the collection of data and management of trials Regulatory requirements worldwide and compliance with the ICH Good Clinical Practice (GCP) Guidelines Development of Standard Operating Procedures for the conduct of clinical trials Complete with chapter summaries that reinforce key points as well as over one hundred examples, Management of Data in Clinical Trials, Second Edition is an ideal resource for practitioners in the clinical research community who are involved in the development of clinical trials, including data managers, research associates, data coordinators, physicians, and statisticians. This book also serves as an excellent supplemental text for courses in clinical trials at both the undergraduate and graduate levels.

At last – a new edition of the highly acclaimed book Clinical Trials in Psychiatry This book provides a concise but thorough overview of clinical trials in psychiatry, invaluable to those seeking solutions to numerous problems relating to design, methodology and analysis of such trials. Practical examples and applications are used to ground theory whenever possible. The Second Edition includes new information regarding: Recent important psychiatric trials More specific discussion of psychiatry in the USA and the particular problems of trials in the USA, including comments about the FDA (U.S. Food and Drug Administration) An extended chapter on meta-analysis Further discussion of sub-group analysis Special features include appendices outlining how to design and report clinical trials, what websites and software programs are appropriate and an extensive reference section. From the reviews of the First Edition: “Everitt & Wessely are to be congratulated on producing an excellent guide to help overcome the snags in clinical trial research. Clearly written and in an engrossing style, the book is likely to become a classic textbook on clinical trials, and not just in psychiatry. The authors’ enthusiasm and grasp of clinical trial research make for a gripping and insightful read…it is one of the very best books that has been written on clinical trials.” THE BRITISH JOURNAL OF PSYCHIATRY "The experience of both authors in this area gives the book a very pragmatic approach grounded in reality, with theoretical overviews invariably being followed by practical examples and applications… an invaluable companion to anyone involved in, or contemplating undertaking, clinical trials research.” PSYCHOLOGICAL MEDICINE

A complete guide to the key statistical concepts essential for the design and construction of clinical trials As the newest major resource in the field of medical research, Methods and Applications of Statistics in Clinical Trials, Volume 1: Concepts, Principles, Trials, and Designs presents a timely and authoritative reviewof the central statistical concepts used to build clinical trials that obtain the best results. The referenceunveils modern approaches vital to understanding, creating, and evaluating data obtained throughoutthe various stages of clinical trial design and analysis. Accessible and comprehensive, the first volume in a two-part set includes newly-written articles as well as established literature from the Wiley Encyclopedia of Clinical Trials. Illustrating a variety of statistical concepts and principles such as longitudinal data, missing data, covariates, biased-coin randomization, repeated measurements, and simple randomization, the book also provides in-depth coverage of the various trial designs found within phase I-IV trials. Methods and Applications of Statistics in Clinical Trials, Volume 1: Concepts, Principles, Trials, and Designs also features: Detailed chapters on the type of trial designs, such as adaptive, crossover, group-randomized, multicenter, non-inferiority, non-randomized, open-labeled, preference, prevention, and superiority trials Over 100 contributions from leading academics, researchers, and practitioners An exploration of ongoing, cutting-edge clinical trials on early cancer and heart disease, mother-to-child human immunodeficiency virus transmission trials, and the AIDS Clinical Trials Group Methods and Applications of Statistics in Clinical Trials, Volume 1: Concepts, Principles, Trials, and Designs is an excellent reference for researchers, practitioners, and students in the fields of clinicaltrials, pharmaceutics, biostatistics, medical research design, biology, biomedicine, epidemiology,and public health.

Presents elements of clinical trial methods that are essential in planning, designing, conducting, analyzing, and interpreting clinical trials with the goal of improving the evidence derived from these important studies This Third Edition builds on the text’s reputation as a straightforward, detailed, and authoritative presentation of quantitative methods for clinical trials. Readers will encounter the principles of design for various types of clinical trials, and are then skillfully guided through the complete process of planning the experiment, assembling a study cohort, assessing data, and reporting results. Throughout the process, the author alerts readers to problems that may arise during the course of the trial and provides common sense solutions. All stages of therapeutic development are discussed in detail, and the methods are not restricted to a single clinical application area. The authors bases current revisions and updates on his own experience, classroom instruction, and feedback from teachers and medical and statistical professionals involved in clinical trials. The Third Edition greatly expands its coverage, ranging from statistical principles to new and provocative topics, including alternative medicine and ethics, middle development, comparative studies, and adaptive designs. At the same time, it offers more pragmatic advice for issues such as selecting outcomes, sample size, analysis, reporting, and handling allegations of misconduct. Readers familiar with the First and Second Editions will discover revamped exercise sets; an updated and extensive reference section; new material on endpoints and the developmental pipeline, among others; and revisions of numerous sections. In addition, this book: • Features accessible and broad coverage of statistical design methods—the crucial building blocks of clinical trials and medical research – now complete with new chapters on overall development, middle development, comparative studies, and adaptive designs • Teaches readers to design clinical trials that produce valid qualitative results backed by rigorous statistical methods • Contains an introduction and summary in each chapter to reinforce key points • Includes discussion questions to stimulate critical thinking and help readers understand how they can apply their newfound knowledge • Provides extensive references to direct readers to the most recent literature, and there are numerous new or revised exercises throughout the book Clinical Trials: A Methodologic Perspective, Third Edition is a textbook accessible to advanced undergraduate students in the quantitative sciences, graduate students in public health and the life sciences, physicians training in clinical research methods, and biostatisticians and epidemiologists. Steven Piantadosi, MD, PhD, is the Phase One Foundation Distinguished Chair and Director of the Samuel Oschin Cancer Institute, and Professor of Medicine at Cedars-Sinai Medical Center in Los Angeles, California. Dr. Piantadosi is one of the world’s leading experts in the design and analysis of clinical trials for cancer research. He has taught clinical trials methods extensively in formal courses and short venues. He has advised numerous academic programs and collaborations nationally regarding clinical trial design and conduct, and has served on external advisory boards for the National Institutes of Health and other prominent cancer programs and centers. The author of more than 260 peer-reviewed scientific articles, Dr. Piantadosi has published extensively on research results, clinical applications, and trial methodology. While his papers have contributed to many areas of oncology, he has also collaborated on diverse studies outside oncology including lung disease and degenerative neurological disease.

This comprehensive, unified text on the principles and practice of clinical trials presents a detailed account of how to conduct the trials. It describes the design, analysis, and interpretation of clinical trials in a non-technical manner and provides a general perspective on their historical development, current status, and future strategy. Features examples derived from the author's personal experience.

Learn rigorous statistical methods to ensure valid clinical trials This Second Edition of the critically hailed Clinical Trials builds on the text's reputation as a straightforward and authoritative presentation of statistical methods for clinical trials. Readers are introduced to the fundamentals of design for various types of clinical trials and then skillfully guided through the complete process of planning the experiment, assembling a study cohort, assessing data, and reporting results. Throughout the process, the author alerts readers to problems that may arise during the course of the trial and provides commonsense solutions. The author bases the revisions and updates on his own classroom experience, as well as feedback from students, instructors, and medical and statistical professionals involved in clinical trials. The Second Edition greatly expands its coverage, ranging from statistical principles to controversial topics, including alternative medicine and ethics. At the same time, it offers more pragmatic advice for issues such as selecting outcomes, sample size, analysis, reporting, and handling allegations of misconduct. Readers familiar with the First Edition will discover completely new chapters, including: * Contexts for clinical trials * Statistical perspectives * Translational clinical trials * Dose-finding and dose-ranging designs Each chapter is accompanied by a summary to reinforce the key points. Revised discussion questions stimulate critical thinking and help readers understand how they can apply their newfound knowledge, and updated references are provided to direct readers to the most recent literature. This text distinguishes itself with its accessible and broad coverage of statistical design methods–the crucial building blocks of clinical trials and medical research. Readers learn to conduct clinical trials that produce valid qualitative results backed by rigorous statistical methods.

There has been substantial growth in the use of data monitoring committees in recent years, by both government agencies and the pharmaceutical industry. This growth has been brought about by increasing recognition of the value of such committees in safeguarding trial participants as well as protecting trial integrity and the validity of conclusions. This very timely book describes the operation of data monitoring committees, and provides an authoritative guide to their establishment, purpose and responsibilities. * Provides a practical overview of data monitoring in clinical trials. * Describes the purpose, responsibilities and operation of data monitoring committees. * Provides directly applicable advice for those managing and conducting clinical trials, and those serving on data monitoring committees. * Gives insight into clinical data monitoring to those sitting on regulatory and ethical committees. * Discusses issues pertinent to those working in clinical trials in both the US and Europe. The practical guidance provided by this book will be of use to professionals working in and/or managing clinical trials, in academic, government and industry settings, particularly medical statisticians, clinicians, trial co-ordinators, and those working in regulatory affairs and bioethics.

Cross-over trials are an important class of design used in the pharmaceutical industry and medical research, and their use continues to grow. Cross-over Trials in Clinical Research, Second Edition has been fully updated to include the latest methodology used in the design and analysis of cross-over trials. It includes more background material, greater coverage of important statistical techniques, including Bayesian methods, and discussion of analysis using a number of statistical software packages. * Comprehensive coverage of the design and analysis of cross-over trials. * Each technique is carefully explained and the mathematics is kept to a minimum. * Features many real and original examples, taken from the author's vast experience. * Includes discussion of analysis using SAS, S-Plus and, GenStat, StatXact and Excel. * Written in a style suitable for statisticians and physicians alike. * Computer programs to accompany the examples in the book can be downloaded from the Web Primarily aimed at statisticians and researchers working in the pharmaceutical industry, the book will also appeal to physicians involved in clinical research and students of medical statistics.

Methods and Applications of Statistics in Clinical Trials, Volume 2: Planning, Analysis, and Inferential Methods includes updates of established literature from the Wiley Encyclopedia of Clinical Trials as well as original material based on the latest developments in clinical trials. Prepared by a leading expert, the second volume includes numerous contributions from current prominent experts in the field of medical research. In addition, the volume features: • Multiple new articles exploring emerging topics, such as evaluation methods with threshold, empirical likelihood methods, nonparametric ROC analysis, over- and under-dispersed models, and multi-armed bandit problems • Up-to-date research on the Cox proportional hazard model, frailty models, trial reports, intrarater reliability, conditional power, and the kappa index • Key qualitative issues including cost-effectiveness analysis, publication bias, and regulatory issues, which are crucial to the planning and data management of clinical trials