Drug development is the process of finding and producing therapeutically useful pharmaceuticals, turning them into safe and effective medicine, and producing reliable information regarding the appropriate dosage and dosing intervals. With regulatory authorities demanding increasingly higher standards in such developments, statistics has become an intrinsic and critical element in the design and conduct of drug development programmes. Statistical Issues in Drug Development presents an essential and thought provoking guide to the statistical issues and controversies involved in drug development. This highly readable second edition has been updated to include: Comprehensive coverage of the design and interpretation of clinical trials. Expanded sections on missing data, equivalence, meta-analysis and dose finding. An examination of both Bayesian and frequentist methods. A new chapter on pharmacogenomics and expanded coverage of pharmaco-epidemiology and pharmaco-economics. Coverage of the ICH guidelines, in particular ICH E9, Statistical Principles for Clinical Trials. It is hoped that the book will stimulate dialogue between statisticians and life scientists working within the pharmaceutical industry. The accessible and wide-ranging coverage make it essential reading for both statisticians and non-statisticians working in the pharmaceutical industry, regulatory bodies and medical research institutes. There is also much to benefit undergraduate and postgraduate students whose courses include a medical statistics component.
In clinical trial practice, controversial statistical issues inevitably occur regardless of the compliance with good statistical practice and good clinical practice. But by identifying the causes of the issues and correcting them, the study objectives of clinical trials can be better achieved. Controversial Statistical Issues in Clinical Trials covers commonly encountered controversial statistical issues in clinical trials and, whenever possible, makes recommendations to resolve these problems. The book focuses on issues occurring at various stages of clinical research and development, including early-phase clinical development (such as bioavailability/bioequivalence), bench-to-bedside translational research, and late-phase clinical development. Numerous examples illustrate the impact of these issues on the evaluation of the safety and efficacy of the test treatment under investigation. The author also offers recommendations regarding possible resolutions of the problems. Written by one of the preeminent experts in the field, this book provides a useful desk reference and state-of-the art examination of problematic issues in clinical trials for scientists in the pharmaceutical industry, medical/statistical reviewers in government regulatory agencies, and researchers and students in academia.
The growth of the pharmaceutical industry over the past decade is astounding, but the impact of this growth on statistics is somewhat confusing. While software has made analysis easier and more efficient, regulatory bodies now demand deeper and more complex analyses, and pharmacogenetic/genomic studies serve up an entirely new set of challenges. For more than two decades, Statistics in the Pharmaceutical Industry has been the definitive guide to sorting through the challenges in the industry, and this Third Edition continues that tradition. Updated and expanded to reflect the most recent trends and developments in the field, Statistics in the Pharmaceutical Industry, Third Edition presents chapters written by experts from both regulatory agencies and pharmaceutical companies who discuss everything from experimental design to post-marketing studies. This approach sheds light on what regulators consider acceptable methodologies and what methods have proven successful for industrial statisticians. Both new and revised chapters reflect the increasingly global nature of the industry as represented by authors from Japan and Europe, the increasing trend toward non-inferiority/equivalence testing, adaptive design in clinical trials, global harmonization of regulatory standards, and multiple comparison studies. The book also examines the latest considerations in anti-cancer studies. Statistics in the Pharmaceutical Industry, Third Edition demystifies the approval process by combining regulatory and industrial points of view, making it a must-read for anyone performing statistical analysis at any point in the drug approval process.
If you have ever wondered when visiting the pharmacy how the dosage of your prescription is determined this book will answer your questions. Dosing information on drug labels is based on discussion between the pharmaceutical manufacturer and the drug regulatory agency, and the label is a summary of results obtained from many scientific experiments. The book introduces the drug development process, the design and the analysis of clinical trials. Many of the discussions are based on applications of statistical methods in the design and analysis of dose response studies. Important procedural steps from a pharmaceutical industry perspective are also examined.
Focusing on the practical clinical and statistical issues that arise in pharmaceutical industry trials, this book summarizes the author’s experience in serving on many data monitoring committees (DMCs) and in heading up a contract research organization that provided statistical support to nearly seventy-five DMCs. It explains the difference in DMC operations between the pharmaceutical industry and National Institutes of Health (NIH)-sponsored trials. Leading you through the types of reports for adverse events and lab values, the author presents the statistical requirements of data monitoring committees and gives advice on how statisticians can best interact with physician members of these committees. He also shows how physicians think differently about safety data than statisticians, proving that both views are needed.
Alex Dmitrienko,Christy Chuang-Stein,Ralph B. D'Agostino
Author: Alex Dmitrienko,Christy Chuang-Stein,Ralph B. D'Agostino
Publisher: SAS Institute
Introduces a range of data analysis problems encountered in drug development and illustrates them using case studies from actual pre-clinical experiments and clinical studies. Includes a discussion of methodological issues, practical advice from subject matter experts, and review of relevant regulatory guidelines.
Statistical Thinking for Non-Statisticians in Drug Regulation, Second Edition, is a need-to-know guide to understanding statistical methodology, statistical data and results within drug development and clinical trials. It provides non-statisticians working in the pharmaceutical and medical device industries with an accessible introduction to the knowledge they need when working with statistical information and communicating with statisticians. It covers the statistical aspects of design, conduct, analysis and presentation of data from clinical trials in drug regulation and improves the ability to read, understand and critically appraise statistical methodology in papers and reports. As such, it is directly concerned with the day-to-day practice and the regulatory requirements of drug development and clinical trials. Fully conversant with current regulatory requirements, this second edition includes five new chapters covering Bayesian statistics, adaptive designs, observational studies, methods for safety analysis and monitoring and statistics for diagnosis. Authored by a respected lecturer and consultant to the pharmaceutical industry, Statistical Thinking for Non-Statisticians in Drug Regulation is an ideal guide for physicians, clinical research scientists, managers and associates, data managers, medical writers, regulatory personnel and for all non-statisticians working and learning within the pharmaceutical industry.
Explore cutting-edge statistical methodologies for collecting, analyzing, and modeling online auction data Online auctions are an increasingly important marketplace, as the new mechanisms and formats underlying these auctions have enabled the capturing and recording of large amounts of bidding data that are used to make important business decisions. As a result, new statistical ideas and innovation are needed to understand bidders, sellers, and prices. Combining methodologies from the fields of statistics, data mining, information systems, and economics, Modeling Online Auctions introduces a new approach to identifying obstacles and asking new questions using online auction data. The authors draw upon their extensive experience to introduce the latest methods for extracting new knowledge from online auction data. Rather than approach the topic from the traditional game-theoretic perspective, the book treats the online auction mechanism as a data generator, outlining methods to collect, explore, model, and forecast data. Topics covered include: Data collection methods for online auctions and related issues that arise in drawing data samples from a Web site Models for bidder and bid arrivals, treating the different approaches for exploring bidder-seller networks Data exploration, such as integration of time series and cross-sectional information; curve clustering; semi-continuous data structures; and data hierarchies The use of functional regression as well as functional differential equation models, spatial models, and stochastic models for capturing relationships in auction data Specialized methods and models for forecasting auction prices and their applications in automated bidding decision rule systems Throughout the book, R and MATLAB software are used for illustrating the discussed techniques. In addition, a related Web site features many of the book's datasets and R and MATLAB code that allow readers to replicate the analyses and learn new methods to apply to their own research. Modeling Online Auctions is a valuable book for graduate-level courses on data mining and applied regression analysis. It is also a one-of-a-kind reference for researchers in the fields of statistics, information systems, business, and marketing who work with electronic data and are looking for new approaches for understanding online auctions and processes. Visit this book's companion website by clicking here
As the development of medicines has become more globalized, the geographic variations in the efficacy and safety of pharmaceutical products need to be addressed. To accelerate the product development process and shorten approval time, researchers are beginning to design multiregional trials that incorporate subjects from many countries around the world under the same protocol. Design and Analysis of Bridging Studies addresses the issues arising from bridging studies and multiregional clinical trials. For bridging studies, the book explores ethnic sensitivity, the necessity of bridging studies, types of bridging studies, and the assessment of similarity between regions based on bridging evidence. For multiregional clinical trials, the text considers regional differences, assesses the consistency of treatment effect across regions, and discusses sample size determination for each region. Taking into account the International Conference Harmonisation (ICH) E5 framework for bridging studies, the book provides a unified summary of the growing literature and research activities in this area. It covers the regulatory requirements, scientific and practical issues, and statistical methodology for designing and evaluating bridging studies and multiregional clinical trials, with the goal of inspiring new research activities in the field.
A practical guide to analysing partially observeddata. Collecting, analysing and drawing inferences from data iscentral to research in the medical and social sciences.Unfortunately, it is rarely possible to collect all the intendeddata. The literature on inference from the resultingincomplete data is now huge, and continues to grow both asmethods are developed for large and complex data structures, and asincreasing computer power and suitable software enable researchersto apply these methods. This book focuses on a particular statistical method foranalysing and drawing inferences from incomplete data, calledMultiple Imputation (MI). MI is attractive because it is bothpractical and widely applicable. The authors aim is to clarify theissues raised by missing data, describing the rationale for MI, therelationship between the various imputation models and associatedalgorithms and its application to increasingly complex datastructures. Multiple Imputation and its Application: Discusses the issues raised by the analysis of partiallyobserved data, and the assumptions on which analyses rest. Presents a practical guide to the issues to consider whenanalysing incomplete data from both observational studies andrandomized trials. Provides a detailed discussion of the practical use of MI withreal-world examples drawn from medical and social statistics. Explores handling non-linear relationships and interactionswith multiple imputation, survival analysis, multilevel multipleimputation, sensitivity analysis via multiple imputation, usingnon-response weights with multiple imputation and doubly robustmultiple imputation. Multiple Imputation and its Application is aimed atquantitative researchers and students in the medical and socialsciences with the aim of clarifying the issues raised by theanalysis of incomplete data data, outlining the rationale for MIand describing how to consider and address the issues that arise inits application.
A fully updated edition of this key text on mixed models,focusing on applications in medical research The application of mixed models is an increasingly popular wayof analysing medical data, particularly in the pharmaceuticalindustry. A mixed model allows the incorporation of both fixed andrandom variables within a statistical analysis, enabling efficientinferences and more information to be gained from the data. Therehave been many recent advances in mixed modelling, particularlyregarding the software and applications. This third edition ofBrown and Prescott’s groundbreaking text provides an updateon the latest developments, and includes guidance on the use ofcurrent SAS techniques across a wide range of applications. Presents an overview of the theory and applications of mixedmodels in medical research, including the latest developments andnew sections on incomplete block designs and the analysis ofbilateral data. Easily accessible to practitioners in any area where mixedmodels are used, including medical statisticians andeconomists. Includes numerous examples using real data from medical andhealth research, and epidemiology, illustrated with SAS code andoutput. Features the new version of SAS, including new graphics formodel diagnostics and the procedure PROC MCMC. Supported by a website featuring computer code, data sets, andfurther material. This third edition will appeal to applied statisticians workingin medical research and the pharmaceutical industry, as well asteachers and students of statistics courses in mixed models. Thebook will also be of great value to a broad range of scientists,particularly those working in the medical and pharmaceuticalareas.
Author: M. D. B. Stephens,John Talbot,Patrick Waller
Publisher: John Wiley & Sons
This text examines the methods for the early detection of adverse drug reactions (ADRs), describing and evaluating working methodologies and techniques. It includes the background to ADRs, methodology for the collection of data and laboratory investigations.
Most questions in social and biomedical sciences are causal in nature: what would happen to individuals, or to groups, if part of their environment were changed? In this groundbreaking text, two world-renowned experts present statistical methods for studying such questions. This book starts with the notion of potential outcomes, each corresponding to the outcome that would be realized if a subject were exposed to a particular treatment or regime. In this approach, causal effects are comparisons of such potential outcomes. The fundamental problem of causal inference is that we can only observe one of the potential outcomes for a particular subject. The authors discuss how randomized experiments allow us to assess causal effects and then turn to observational studies. They lay out the assumptions needed for causal inference and describe the leading analysis methods, including matching, propensity-score methods, and instrumental variables. Many detailed applications are included, with special focus on practical aspects for the empirical researcher.
This book presents new and powerful advanced statistical methods that have been used in modern medicine, drug development, and epidemiology. Some of these methods were initially developed for tackling medical problems. All 29 chapters are self-contained. Each chapter represents the new development and future research topics for a medical or statistical branch. For the benefit of readers with different statistical background, each chapter follows a similar style: the explanation of medical challenges, statistical ideas and strategies, statistical methods and techniques, mathematical remarks and background and reference. All chapters are written by experts of the respective topics.
Author: Morris J. Brown,Pankaj Sharma,Peter N. Bennett
Publisher: Elsevier Health Sciences
A thorough knowledge of pharmacological and therapeutic principles is vital if drugs are to be used safely and effectively for increasingly informed patients. Those who clearly understand how drugs get into the body, how they produce their effects, what happens to them in the body, and how evidence of their therapeutic effect is assessed, will choose drugs more skilfully, and use them more safely and successfully than those who do not. Now in a fully revised 11th edition, Clinical Pharmacology is essential reading for undergraduate medical students, junior doctors and anyone concerned with evidence-based drug therapy. Introductory first three sections cover general principle of clinical pharmacology; five subsequent sections cover drug treatment of disease organised by body system. Retains approachable style set by the original author, Professor Laurence. Emphasis throughout is on evidence-based and safe drug prescribing. Indian Advisory Board will ensure content reflects the needs of the devloping world.