Group Sequential And Confirmatory Adaptive Designs In Clinical Trials

Author : Gernot Wassmer,Werner Brannath
Publisher : Springer
Page : 301 pages
File Size : 45,7 Mb
Release : 2016-07-04
Category : Medical
ISBN : 9783319325620

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Group Sequential and Confirmatory Adaptive Designs in Clinical Trials by Gernot Wassmer,Werner Brannath Pdf

This book provides an up-to-date review of the general principles of and techniques for confirmatory adaptive designs. Confirmatory adaptive designs are a generalization of group sequential designs. With these designs, interim analyses are performed in order to stop the trial prematurely under control of the Type I error rate. In adaptive designs, it is also permissible to perform a data-driven change of relevant aspects of the study design at interim stages. This includes, for example, a sample-size reassessment, a treatment-arm selection or a selection of a pre-specified sub-population. Essentially, this adaptive methodology was introduced in the 1990s. Since then, it has become popular and the object of intense discussion and still represents a rapidly growing field of statistical research. This book describes adaptive design methodology at an elementary level, while also considering designing and planning issues as well as methods for analyzing an adaptively planned trial. This includes estimation methods and methods for the determination of an overall p-value. Part I of the book provides the group sequential methods that are necessary for understanding and applying the adaptive design methodology supplied in Parts II and III of the book. The book contains many examples that illustrate use of the methods for practical application. The book is primarily written for applied statisticians from academia and industry who are interested in confirmatory adaptive designs. It is assumed that readers are familiar with the basic principles of descriptive statistics, parameter estimation and statistical testing. This book will also be suitable for an advanced statistical course for applied statisticians or clinicians with a sound statistical background.

Author : Jay Bartroff,Tze Leung Lai,Mei-Chiung Shih
Publisher : Springer Science & Business Media
Page : 250 pages
File Size : 42,8 Mb
Release : 2012-12-12
Category : Medical
ISBN : 9781461461142

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Sequential Experimentation in Clinical Trials by Jay Bartroff,Tze Leung Lai,Mei-Chiung Shih Pdf

Sequential Experimentation in Clinical Trials: Design and Analysis is developed from decades of work in research groups, statistical pedagogy, and workshop participation. Different parts of the book can be used for short courses on clinical trials, translational medical research, and sequential experimentation. The authors have successfully used the book to teach innovative clinical trial designs and statistical methods for Statistics Ph.D. students at Stanford University. There are additional online supplements for the book that include chapter-specific exercises and information. Sequential Experimentation in Clinical Trials: Design and Analysis covers the much broader subject of sequential experimentation that includes group sequential and adaptive designs of Phase II and III clinical trials, which have attracted much attention in the past three decades. In particular, the broad scope of design and analysis problems in sequential experimentation clearly requires a wide range of statistical methods and models from nonlinear regression analysis, experimental design, dynamic programming, survival analysis, resampling, and likelihood and Bayesian inference. The background material in these building blocks is summarized in Chapter 2 and Chapter 3 and certain sections in Chapter 6 and Chapter 7. Besides group sequential tests and adaptive designs, the book also introduces sequential change-point detection methods in Chapter 5 in connection with pharmacovigilance and public health surveillance. Together with dynamic programming and approximate dynamic programming in Chapter 3, the book therefore covers all basic topics for a graduate course in sequential analysis designs.

Author : Shein-Chung Chow,Mark Chang
Publisher : CRC Press
Page : 368 pages
File Size : 40,6 Mb
Release : 2011-12-01
Category : Mathematics
ISBN : 9781439839881

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Adaptive Design Methods in Clinical Trials by Shein-Chung Chow,Mark Chang Pdf

With new statistical and scientific issues arising in adaptive clinical trial design, including the U.S. FDA's recent draft guidance, a new edition of one of the first books on the topic is needed. Adaptive Design Methods in Clinical Trials, Second Edition reflects recent developments and regulatory positions on the use of adaptive designs in clini

Author : Weili He,José Pinheiro,Olga M. Kuznetsova
Publisher : Springer
Page : 416 pages
File Size : 52,5 Mb
Release : 2014-10-15
Category : Medical
ISBN : 9781493911004

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Practical Considerations for Adaptive Trial Design and Implementation by Weili He,José Pinheiro,Olga M. Kuznetsova Pdf

This edited volume is a definitive text on adaptive clinical trial designs from creation and customization to utilization. As this book covers the full spectrum of topics involved in the adaptive designs arena, it will serve as a valuable reference for researchers working in industry, government and academia. The target audience is anyone involved in the planning and execution of clinical trials, in particular, statisticians, clinicians, pharmacometricians, clinical operation specialists, drug supply managers, and infrastructure providers. In spite of the increased efficiency of adaptive trials in saving costs and time, ultimately getting drugs to patients sooner, their adoption in clinical development is still relatively low. One of the chief reasons is the higher complexity of adaptive design trials as compared to traditional trials. Barriers to the use of clinical trials with adaptive features include the concerns about the integrity of study design and conduct, the risk of regulatory non-acceptance, the need for an advanced infrastructure for complex randomization and clinical supply scenarios, change management for process and behavior modifications, extensive resource requirements for the planning and design of adaptive trials and the potential to relegate key decision makings to outside entities. There have been limited publications that address these practical considerations and recommend best practices and solutions. This book fills this publication gap, providing guidance on practical considerations for adaptive trial design and implementation. The book comprises three parts: Part I focuses on practical considerations from a design perspective, whereas Part II delineates practical considerations related to the implementation of adaptive trials. Putting it all together, Part III presents four illustrative case studies ranging from description and discussion of specific adaptive trial design considerations to the logistic and regulatory issues faced in trial implementation. Bringing together the expertise of leading key opinion leaders from pharmaceutical industry, academia, and regulatory agencies, this book provides a balanced and comprehensive coverage of practical considerations for adaptive trial design and implementation.

Author : John Whitehead
Publisher : Horwood Publishing Limited
Page : 280 pages
File Size : 40,7 Mb
Release : 1983
Category : Health & Fitness
ISBN : UOM:39015015600102

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The Design and Analysis of Sequential Clinical Trials by John Whitehead Pdf

This book details all aspects of sequential clinical trials from preliminary planning, through the monitoring of the trial, to the final analysis of the results.

Author : Institute of Medicine,Board on Health Sciences Policy,Committee on Strategies for Small-Number-Participant Clinical Research Trials
Publisher : National Academies Press
Page : 222 pages
File Size : 42,7 Mb
Release : 2001-01-01
Category : Medical
ISBN : 0309171148

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Small Clinical Trials by Institute of Medicine,Board on Health Sciences Policy,Committee on Strategies for Small-Number-Participant Clinical Research Trials Pdf

Clinical trials are used to elucidate the most appropriate preventive, diagnostic, or treatment options for individuals with a given medical condition. Perhaps the most essential feature of a clinical trial is that it aims to use results based on a limited sample of research participants to see if the intervention is safe and effective or if it is comparable to a comparison treatment. Sample size is a crucial component of any clinical trial. A trial with a small number of research participants is more prone to variability and carries a considerable risk of failing to demonstrate the effectiveness of a given intervention when one really is present. This may occur in phase I (safety and pharmacologic profiles), II (pilot efficacy evaluation), and III (extensive assessment of safety and efficacy) trials. Although phase I and II studies may have smaller sample sizes, they usually have adequate statistical power, which is the committee's definition of a "large" trial. Sometimes a trial with eight participants may have adequate statistical power, statistical power being the probability of rejecting the null hypothesis when the hypothesis is false. Small Clinical Trials assesses the current methodologies and the appropriate situations for the conduct of clinical trials with small sample sizes. This report assesses the published literature on various strategies such as (1) meta-analysis to combine disparate information from several studies including Bayesian techniques as in the confidence profile method and (2) other alternatives such as assessing therapeutic results in a single treated population (e.g., astronauts) by sequentially measuring whether the intervention is falling above or below a preestablished probability outcome range and meeting predesigned specifications as opposed to incremental improvement.

Author : William F. Rosenberger,John M. Lachin
Publisher : John Wiley & Sons
Page : 284 pages
File Size : 55,9 Mb
Release : 2015-11-23
Category : Mathematics
ISBN : 9781118742242

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Randomization in Clinical Trials by William F. Rosenberger,John M. Lachin Pdf

Praise for the First Edition “All medical statisticians involved in clinical trials should read this book…” - Controlled Clinical Trials Featuring a unique combination of the applied aspects of randomization in clinical trials with a nonparametric approach to inference, Randomization in Clinical Trials: Theory and Practice, Second Edition is the go-to guide for biostatisticians and pharmaceutical industry statisticians. Randomization in Clinical Trials: Theory and Practice, Second Edition features: Discussions on current philosophies, controversies, and new developments in the increasingly important role of randomization techniques in clinical trials A new chapter on covariate-adaptive randomization, including minimization techniques and inference New developments in restricted randomization and an increased focus on computation of randomization tests as opposed to the asymptotic theory of randomization tests Plenty of problem sets, theoretical exercises, and short computer simulations using SAS® to facilitate classroom teaching, simplify the mathematics, and ease readers’ understanding Randomization in Clinical Trials: Theory and Practice, Second Edition is an excellent reference for researchers as well as applied statisticians and biostatisticians. The Second Edition is also an ideal textbook for upper-undergraduate and graduate-level courses in biostatistics and applied statistics. William F. Rosenberger, PhD, is University Professor and Chairman of the Department of Statistics at George Mason University. He is a Fellow of the American Statistical Association and the Institute of Mathematical Statistics, and author of over 80 refereed journal articles, as well as The Theory of Response-Adaptive Randomization in Clinical Trials, also published by Wiley. John M. Lachin, ScD, is Research Professor in the Department of Epidemiology and Biostatistics as well as in the Department of Statistics at The George Washington University. A Fellow of the American Statistical Association and the Society for Clinical Trials, Dr. Lachin is actively involved in coordinating center activities for clinical trials of diabetes. He is the author of Biostatistical Methods: The Assessment of Relative Risks, Second Edition, also published by Wiley.

Author : Scott M. Berry,Bradley P. Carlin,J. Jack Lee,Peter Muller
Publisher : CRC Press
Page : 316 pages
File Size : 40,9 Mb
Release : 2010-07-19
Category : Mathematics
ISBN : 9781439825518

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Bayesian Adaptive Methods for Clinical Trials by Scott M. Berry,Bradley P. Carlin,J. Jack Lee,Peter Muller Pdf

Already popular in the analysis of medical device trials, adaptive Bayesian designs are increasingly being used in drug development for a wide variety of diseases and conditions, from Alzheimer's disease and multiple sclerosis to obesity, diabetes, hepatitis C, and HIV. Written by leading pioneers of Bayesian clinical trial designs, Bayesian Adapti

Author : Christopher Jennison,Bruce W. Turnbull
Publisher : CRC Press
Page : 416 pages
File Size : 45,6 Mb
Release : 1999-09-15
Category : Mathematics
ISBN : 158488858X

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Group Sequential Methods with Applications to Clinical Trials by Christopher Jennison,Bruce W. Turnbull Pdf

Group sequential methods answer the needs of clinical trial monitoring committees who must assess the data available at an interim analysis. These interim results may provide grounds for terminating the study-effectively reducing costs-or may benefit the general patient population by allowing early dissemination of its findings. Group sequential methods provide a means to balance the ethical and financial advantages of stopping a study early against the risk of an incorrect conclusion. Group Sequential Methods with Applications to Clinical Trials describes group sequential stopping rules designed to reduce average study length and control Type I and II error probabilities. The authors present one-sided and two-sided tests, introduce several families of group sequential tests, and explain how to choose the most appropriate test and interim analysis schedule. Their topics include placebo-controlled randomized trials, bio-equivalence testing, crossover and longitudinal studies, and linear and generalized linear models. Research in group sequential analysis has progressed rapidly over the past 20 years. Group Sequential Methods with Applications to Clinical Trials surveys and extends current methods for planning and conducting interim analyses. It provides straightforward descriptions of group sequential hypothesis tests in a form suited for direct application to a wide variety of clinical trials. Medical statisticians engaged in any investigations planned with interim analyses will find this book a useful and important tool.

Author : Cyrus Mehta,Martin Posch
Publisher : Wiley-Blackwell
Page : 288 pages
File Size : 55,9 Mb
Release : 2013-08-23
Category : Electronic
ISBN : 0470682264

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Adaptive Designs for Confirmatory Clinical Trials by Cyrus Mehta,Martin Posch Pdf

Author : Mark Chang
Publisher : CRC Press
Page : 709 pages
File Size : 44,5 Mb
Release : 2014-12-01
Category : Mathematics
ISBN : 9781482256598

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Adaptive Design Theory and Implementation Using SAS and R, Second Edition by Mark Chang Pdf

Get Up to Speed on Many Types of Adaptive Designs Since the publication of the first edition, there have been remarkable advances in the methodology and application of adaptive trials. Incorporating many of these new developments, Adaptive Design Theory and Implementation Using SAS and R, Second Edition offers a detailed framework to understand the use of various adaptive design methods in clinical trials. New to the Second Edition Twelve new chapters covering blinded and semi-blinded sample size reestimation design, pick-the-winners design, biomarker-informed adaptive design, Bayesian designs, adaptive multiregional trial design, SAS and R for group sequential design, and much more More analytical methods for K-stage adaptive designs, multiple-endpoint adaptive design, survival modeling, and adaptive treatment switching New material on sequential parallel designs with rerandomization and the skeleton approach in adaptive dose-escalation trials Twenty new SAS macros and R functions Enhanced end-of-chapter problems that give readers hands-on practice addressing issues encountered in designing real-life adaptive trials Covering even more adaptive designs, this book provides biostatisticians, clinical scientists, and regulatory reviewers with up-to-date details on this innovative area in pharmaceutical research and development. Practitioners will be able to improve the efficiency of their trial design, thereby reducing the time and cost of drug development.

Author : Toshimitsu Hamasaki,Koko Asakura,Scott R. Evans,Toshimitsu Ochiai
Publisher : Springer
Page : 113 pages
File Size : 40,8 Mb
Release : 2016-06-01
Category : Mathematics
ISBN : 9784431559009

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Group-Sequential Clinical Trials with Multiple Co-Objectives by Toshimitsu Hamasaki,Koko Asakura,Scott R. Evans,Toshimitsu Ochiai Pdf

This book focuses on group sequential methods for clinical trials with co-primary endpoints based on the decision-making frameworks for: (1) rejecting the null hypothesis (stopping for efficacy), (2) rejecting the alternative hypothesis (stopping for futility), and (3) rejecting the null or alternative hypothesis (stopping for either futility or efficacy), where the trial is designed to evaluate whether the intervention is superior to the control on all endpoints. For assessing futility, there are two fundamental approaches, i.e., the decision to stop for futility based on the conditional probability of rejecting the null hypothesis, and the other based on stopping boundaries using group sequential methods. In this book, the latter approach is discussed. The book also briefly deals with the group sequential methods for clinical trials designed to evaluate whether the intervention is superior to the control on at least one endpoint. In addition, the book describes sample size recalculation and the resulting effect on power and type I error rate. The book also describes group sequential strategies for three-arm clinical trials to demonstrate the non-inferiority of experimental intervention to actively control and to assess the assay sensitivity to placebo control.

Author : Sandeep Menon,Richard C. Zink
Publisher : SAS Institute
Page : 482 pages
File Size : 53,8 Mb
Release : 2015-12-09
Category : Computers
ISBN : 9781629600826

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Modern Approaches to Clinical Trials Using SAS by Sandeep Menon,Richard C. Zink Pdf

Get the tools you need to use SAS® in clinical trial design! Unique and multifaceted, Modern Approaches to Clinical Trials Using SAS: Classical, Adaptive, and Bayesian Methods, edited by Sandeep M. Menon and Richard C. Zink, thoroughly covers several domains of modern clinical trial design: classical, group sequential, adaptive, and Bayesian methods that are applicable to and widely used in various phases of pharmaceutical development. Written for biostatisticians, pharmacometricians, clinical developers, and statistical programmers involved in the design, analysis, and interpretation of clinical trials, as well as students in graduate and postgraduate programs in statistics or biostatistics, the book touches on a wide variety of topics, including dose-response and dose-escalation designs; sequential methods to stop trials early for overwhelming efficacy, safety, or futility; Bayesian designs that incorporate historical data; adaptive sample size re-estimation; adaptive randomization to allocate subjects to more effective treatments; and population enrichment designs. Methods are illustrated using clinical trials from diverse therapeutic areas, including dermatology, endocrinology, infectious disease, neurology, oncology, and rheumatology. Individual chapters are authored by renowned contributors, experts, and key opinion leaders from the pharmaceutical/medical device industry or academia. Numerous real-world examples and sample SAS code enable users to readily apply novel clinical trial design and analysis methodologies in practice.

Author : David Harrington
Publisher : Springer Science & Business Media
Page : 206 pages
File Size : 40,7 Mb
Release : 2011-10-09
Category : Medical
ISBN : 1461401402

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Designs for Clinical Trials by David Harrington Pdf

This book will examine current issues and controversies in the design of clinical trials, including topics in adaptive and sequential designs, the design of correlative genomic studies, the design of studies in which missing data is anticipated. Each chapter will be written by an expert conducting research in the topic of that chapter. As a collection, the chapters would be intended to serve as a guidance for statisticians designing trials.

Author : David M. Murray
Publisher : Monographs in Epidemiology and
Page : 481 pages
File Size : 43,8 Mb
Release : 1998
Category : Medical
ISBN : 9780195120363

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Design and Analysis of Group-randomized Trials by David M. Murray Pdf

Community or group-randomized trials, which are usually done to evaluate the effect of health promotion effors. It reviews the underlying issues, describes the most widely used research design, and presents the many approaches to analysis that are now available.