Clinical Trial Design. Bayesian and Frequentist Adaptive Methods

A balanced treatment of the theories, methodologies, and design issues involved in clinical trials using statistical methods There has been enormous interest and development in Bayesian adaptive designs, especially for early phases of clinical trials. However, for phase III trials, frequentist methods still play a dominant role through controlling type I and type II errors in the hypothesis testing framework. From practical perspectives, Clinical Trial Design: Bayesian and Frequentist Adaptive Methods provides comprehensive coverage of both Bayesian and frequentist approaches to all phases of clinical trial design. Before underpinning various adaptive methods, the book establishes an overview of the fundamentals of clinical trials as well as a comparison of Bayesian and frequentist statistics. Recognizing that clinical trial design is one of the most important and useful skills in the pharmaceutical industry, this book provides detailed discussions on a variety of statistical designs, their properties, and operating characteristics for phase I, II, and III clinical trials as well as an introduction to phase IV trials. Many practical issues and challenges arising in clinical trials are addressed. Additional topics of coverage include: Risk and benefit analysis for toxicity and efficacy trade-offs Bayesian predictive probability trial monitoring Bayesian adaptive randomization Late onset toxicity and response Dose finding in drug combination trials Targeted therapy designs The author utilizes cutting-edge clinical trial designs and statistical methods that have been employed at the world's leading medical centers as well as in the pharmaceutical industry. The software used throughout the book is freely available on the book's related website, equipping readers with the necessary tools for designing clinical trials. Clinical Trial Design is an excellent book for courses on the topic at the graduate level. The book also serves as a valuable reference for statisticians and biostatisticians in the pharmaceutical industry as well as for researchers and practitioners who design, conduct, and monitor clinical trials in their everyday work.

How to conduct clinical trials in an ethical and scientifically responsible manner This book presents a methodology for clinical trials that produces improved health outcomes for patients while obtaining sound and unambiguous scientific data. It centers around a real-world test case–involving a treatment for hypertension after open heart surgery–and explains how to use Bayesian methods to accommodate both ethical and scientific imperatives. The book grew out of the direct involvement in the project by a diverse group of experts in medicine, statistics, philosophy, and the law. Not only do they contribute essays on the scientific, technological, legal, and ethical aspects of clinical trials, but they also critique and debate each other's opinions, creating an interesting, personalized text. Bayesian Methods and Ethics in a Clinical Trial Design * Answers commonly raised questions about Bayesian methods * Describes the advantages and disadvantages of this method compared with other methods * Applies current ethical theory to a particular class of design for clinical trials * Discusses issues of informed consent and how to serve a patient's best interest while still obtaining uncontaminated scientific data * Shows how to use Bayesian probabilistic methods to create computer models from elicited prior opinions of medical experts on the best treatment for a type of patient * Contains several chapters on the process, results, and computational aspects of the test case in question * Explores American law and the legal ramifications of using human subjects For statisticians and biostatisticians, and for anyone involved with medicine and public health, this book provides both a practical guide and a unique perspective on the connection between technological developments, human factors, and some of the larger ethical issues of our times.

The first all-inclusive introduction to modern statistical research methods in the natural resource sciences The use of Bayesian statistical analysis has become increasingly important to natural resource scientists as a practical tool for solving various research problems. However, many important contemporary methods of applied statistics, such as generalized linear modeling, mixed-effects modeling, and Bayesian statistical analysis and inference, remain relatively unknown among researchers and practitioners in this field. Through its inclusive, hands-on treatment of real-world examples, Contemporary Bayesian and Frequentist Statistical Research Methods for Natural Resource Scientists successfully introduces the key concepts of statistical analysis and inference with an accessible, easy-to-follow approach. The book provides case studies illustrating common problems that exist in the natural resource sciences and presents the statistical knowledge and tools needed for a modern treatment of these issues. Subsequent chapter coverage features: An introduction to the fundamental concepts of Bayesian statistical analysis, including its historical background, conjugate solutions, Bayesian hypothesis testing and decision-making, and Markov Chain Monte Carlo solutions The relevant advantages of using Bayesian statistical analysis, rather than the traditional frequentist approach, to address research problems Two alternative strategies?€”the a posteriori model selection strategy and the a priori parsimonious model selection strategy using AIC and DIC?€”to model selection and inference The ideas of generalized linear modeling (GLM), focusing on the most popular GLM of logistic regression An introduction to mixed-effects modeling in S-Plus?® and R for analyzing natural resource data sets with varying error structures and dependencies Each statistical concept is accompanied by an illustration of its frequentist application in S-Plus?® or R as well as its Bayesian application in WinBUGS. Brief introductions to these software packages are also provided to help the reader fully understand the concepts of the statistical methods that are presented throughout the book. Assuming only a minimal background in introductory statistics, Contemporary Bayesian and Frequentist Statistical Research Methods for Natural Resource Scientists is an ideal text for natural resource students studying statistical research methods at the upper-undergraduate or graduate level and also serves as a valuable problem-solving guide for natural resource scientists across a broad range of disciplines, including biology, wildlife management, forestry management, fisheries management, and the environmental sciences.

ExpDesign Studio facilitates more efficient clinical trial design This book introduces pharmaceutical statisticians, scientists, researchers, and others to ExpDesign Studio software for classical and adaptive designs of clinical trials. It includes the Professional Version 5.0 of ExpDesign Studio software that frees pharmaceutical professionals to focus on drug development and related challenges while the software handles the essential calculations and computations. After a hands-on introduction to the software and an overview of clinical trial designs encompassing numerous variations, Classical and Adaptive Clinical Trial Designs Using ExpDesign Studio: Covers both classical and adaptive clinical trial designs, monitoring, and analyses Explains various classical and adaptive designs including groupsequential, sample-size reestimation, dropping-loser, biomarker-adaptive, and response-adaptive randomization designs Includes instructions for over 100 design methods that have been implemented in ExpDesign Studio and step-by-step demos as well as real-world examples Emphasizes applications, yet covers key mathematical formulations Introduces readers to additional toolkits in ExpDesign Studio that help in designing, monitoring, and analyzing trials, such as the adaptive monitor, graphical calculator, the probability calculator, the confidence interval calculator, and more Presents comprehensive technique notes for sample-size calculation methods, grouped by the number of arms, the trial endpoint, and the analysis basis Written with practitioners in mind, this is an ideal self-study guide for not only statisticians, but also scientists, researchers, and professionals in the pharmaceutical industry, contract research organizations (CROs), and regulatory bodies. It's also a go-to reference for biostatisticians, pharmacokinetic specialists, and principal investigators involved in clinical trials. ERRATUM Classical and Adaptive Clinical Trial Designs Using ExpDesign Studio By Mark Chang The license for the ExpDesign Studio software on the CD included with this book is good for one-year after installation of the software. Prior to the expiration of this period, the software will generate a reminder about renewal for the license. The user should contact CTriSoft International (the owners of ExpDesign Studio) at www.CTriSoft.net or by email at license@ctrisoft.net, about renewal for the license. This should have been made clear in the first printing of this book. We apologize for this error.

HIGHLIGHTS THE USE OF BAYESIAN STATISTICS TO GAIN INSIGHTS FROM EMPIRICAL DATA Featuring an accessible approach, Bayesian Methods for Management and Business: Pragmatic Solutions for Real Problems demonstrates how Bayesian statistics can help to provide insights into important issues facing business and management. The book draws on multidisciplinary applications and examples and utilizes the freely available software WinBUGS and R to illustrate the integration of Bayesian statistics within data-rich environments. Computational issues are discussed and integrated with coverage of linear models, sensitivity analysis, Markov Chain Monte Carlo (MCMC), and model comparison. In addition, more advanced models including hierarchal models, generalized linear models, and latent variable models are presented to further bridge the theory and application in real-world usage. Bayesian Methods for Management and Business: Pragmatic Solutions for Real Problems also features: Numerous real-world examples drawn from multiple management disciplines such as strategy, international business, accounting, and information systems An incremental skill-building presentation based on analyzing data sets with widely applicable models of increasing complexity An accessible treatment of Bayesian statistics that is integrated with a broad range of business and management issues and problems A practical problem-solving approach to illustrate how Bayesian statistics can help to provide insight into important issues facing business and management Bayesian Methods for Management and Business: Pragmatic Solutions for Real Problems is an important textbook for Bayesian statistics courses at the advanced MBA-level and also for business and management PhD candidates as a first course in methodology. In addition, the book is a useful resource for management scholars and practitioners as well as business academics and practitioners who seek to broaden their methodological skill sets.

Bayesian methods are a powerful tool in many areas of science and engineering, especially statistical physics, medical sciences, electrical engineering, and information sciences. They are also ideal for civil engineering applications, given the numerous types of modeling and parametric uncertainty in civil engineering problems. For example, earthquake ground motion cannot be predetermined at the structural design stage. Complete wind pressure profiles are difficult to measure under operating conditions. Material properties can be difficult to determine to a very precise level – especially concrete, rock, and soil. For air quality prediction, it is difficult to measure the hourly/daily pollutants generated by cars and factories within the area of concern. It is also difficult to obtain the updated air quality information of the surrounding cities. Furthermore, the meteorological conditions of the day for prediction are also uncertain. These are just some of the civil engineering examples to which Bayesian probabilistic methods are applicable. Familiarizes readers with the latest developments in the field Includes identification problems for both dynamic and static systems Addresses challenging civil engineering problems such as modal/model updating Presents methods applicable to mechanical and aerospace engineering Gives engineers and engineering students a concrete sense of implementation Covers real-world case studies in civil engineering and beyond, such as: structural health monitoring seismic attenuation finite-element model updating hydraulic jump artificial neural network for damage detection air quality prediction Includes other insightful daily-life examples Companion website with MATLAB code downloads for independent practice Written by a leading expert in the use of Bayesian methods for civil engineering problems This book is ideal for researchers and graduate students in civil and mechanical engineering or applied probability and statistics. Practicing engineers interested in the application of statistical methods to solve engineering problems will also find this to be a valuable text. MATLAB code and lecture materials for instructors available at http://www.wiley.com/go/yuen

READ ALL ABOUT IT! David Spiegelhalter has recently joined the ranks of Isaac Newton, Charles Darwin and Stephen Hawking by becoming a fellow of the Royal Society. Originating from the Medical Research Council’s biostatistics unit, David has played a leading role in the Bristol heart surgery and Harold Shipman inquiries. Order a copy of this author’s comprehensive text TODAY! The Bayesian approach involves synthesising data and judgement in order to reach conclusions about unknown quantities and make predictions. Bayesian methods have become increasingly popular in recent years, notably in medical research, and although there are a number of books on Bayesian analysis, few cover clinical trials and biostatistical applications in any detail. Bayesian Approaches to Clinical Trials and Health-Care Evaluation provides a valuable overview of this rapidly evolving field, including basic Bayesian ideas, prior distributions, clinical trials, observational studies, evidence synthesis and cost-effectiveness analysis. Covers a broad array of essential topics, building from the basics to more advanced techniques. Illustrated throughout by detailed case studies and worked examples Includes exercises in all chapters Accessible to anyone with a basic knowledge of statistics Authors are at the forefront of research into Bayesian methods in medical research Accompanied by a Web site featuring data sets and worked examples using Excel and WinBUGS – the most widely used Bayesian modelling package Bayesian Approaches to Clinical Trials and Health-Care Evaluation is suitable for students and researchers in medical statistics, statisticians in the pharmaceutical industry, and anyone involved in conducting clinical trials and assessment of health-care technology.

A systematic approach to all aspects of designing and conducting clinical trials The success or failure of clinical trials hinges on hundreds of details that need to be developed, often under less than ideal conditions. Written by one of the world's leading trialists, Clinical Trials Handbook: Design and Conduct provides clinicians with a complete guide to designing, conducting, and evaluating clinical trials—teaching them how to simplify the process and avoid costly mistakes. The author draws on his extensive clinical trials experience to outline all steps employed in setting up and running clinical trials, from budgeting and fundraising to publishing the results. Along the way, practical advice is offered while also addressing a mix of logistical, ethical, psychological, behavioral, and administrative issues inherent to clinical trials. Topics of coverage include: Protocols for drug masking, controls, and treatment randomization Consent, enrollment, eligibility, and follow-up procedures Different types of sample size design and data collection and processing Working with study centers, research staff, and various committees Monitoring treatment effects and performance, and ensuring quality control Data analysis and access policies for study data and documents Clinical Trials Handbook is invaluable for practicing clinicians and trialists who would like to learn more about or improve their understanding of the design and execution of clinical trials. The book is also an excellent supplement for courses on clinical trials at the graduate level.

The focus of this book is on «ill-posed inverse problems». These problems cannot be solved only on the basis of observed data. The building of solutions involves the recognition of other pieces of a priori information. These solutions are then specific to the pieces of information taken into account. Clarifying and taking these pieces of information into account is necessary for grasping the domain of validity and the field of application for the solutions built. For too long, the interest in these problems has remained very limited in the signal-image community. However, the community has since recognized that these matters are more interesting and they have become the subject of much greater enthusiasm. From the application field’s point of view, a significant part of the book is devoted to conventional subjects in the field of inversion: biological and medical imaging, astronomy, non-destructive evaluation, processing of video sequences, target tracking, sensor networks and digital communications. The variety of chapters is also clear, when we examine the acquisition modalities at stake: conventional modalities, such as tomography and NMR, visible or infrared optical imaging, or more recent modalities such as atomic force imaging and polarized light imaging.

The past decade has seen a dramatic increase in the use of Bayesian methods in marketing due, in part, to computational and modelling breakthroughs, making its implementation ideal for many marketing problems. Bayesian analyses can now be conducted over a wide range of marketing problems, from new product introduction to pricing, and with a wide variety of different data sources. Bayesian Statistics and Marketing describes the basic advantages of the Bayesian approach, detailing the nature of the computational revolution. Examples contained include household and consumer panel data on product purchases and survey data, demand models based on micro-economic theory and random effect models used to pool data among respondents. The book also discusses the theory and practical use of MCMC methods. Written by the leading experts in the field, this unique book: Presents a unified treatment of Bayesian methods in marketing, with common notation and algorithms for estimating the models. Provides a self-contained introduction to Bayesian methods. Includes case studies drawn from the authors’ recent research to illustrate how Bayesian methods can be extended to apply to many important marketing problems. Is accompanied by an R package, bayesm, which implements all of the models and methods in the book and includes many datasets. In addition the book’s website hosts datasets and R code for the case studies. Bayesian Statistics and Marketing provides a platform for researchers in marketing to analyse their data with state-of-the-art methods and develop new models of consumer behaviour. It provides a unified reference for cutting-edge marketing researchers, as well as an invaluable guide to this growing area for both graduate students and professors, alike.