Multiple Testing Problems in Pharmaceutical Statistics PDF Download

Author: Alex Dmitrienko
Publisher: CRC Press
ISBN: 1584889853
Category : Mathematics
Languages : en
Pages : 323

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Book Description
Useful Statistical Approaches for Addressing Multiplicity IssuesIncludes practical examples from recent trials Bringing together leading statisticians, scientists, and clinicians from the pharmaceutical industry, academia, and regulatory agencies, Multiple Testing Problems in Pharmaceutical Statistics explores the rapidly growing area of multiple c

Author: Frank Bretz
Publisher: CRC Press
ISBN: 1420010905
Category : Mathematics
Languages : en
Pages : 202

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Book Description
Adopting a unifying theme based on maximum statistics, Multiple Comparisons Using R describes the common underlying theory of multiple comparison procedures through numerous examples. It also presents a detailed description of available software implementations in R. The R packages and source code for the analyses are available at http://CRAN.R-project.org After giving examples of multiplicity problems, the book covers general concepts and basic multiple comparisons procedures, including the Bonferroni method and Simes’ test. It then shows how to perform parametric multiple comparisons in standard linear models and general parametric models. It also introduces the multcomp package in R, which offers a convenient interface to perform multiple comparisons in a general context. Following this theoretical framework, the book explores applications involving the Dunnett test, Tukey’s all pairwise comparisons, and general multiple contrast tests for standard regression models, mixed-effects models, and parametric survival models. The last chapter reviews other multiple comparison procedures, such as resampling-based procedures, methods for group sequential or adaptive designs, and the combination of multiple comparison procedures with modeling techniques. Controlling multiplicity in experiments ensures better decision making and safeguards against false claims. A self-contained introduction to multiple comparison procedures, this book offers strategies for constructing the procedures and illustrates the framework for multiple hypotheses testing in general parametric models. It is suitable for readers with R experience but limited knowledge of multiple comparison procedures and vice versa. See Dr. Bretz discuss the book.

Author: Alex Dmitrienko, Ph.D.
Publisher: SAS Institute
ISBN: 1629590304
Category : Computers
Languages : en
Pages : 464

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Book Description
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.

Author: Institute of Medicine
Publisher: National Academies Press
ISBN: 0309171148
Category : Medical
Languages : en
Pages : 221

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Book Description
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: Deborah G. Mayo
Publisher: Cambridge University Press
ISBN: 1108563309
Category : Mathematics
Languages : en
Pages : 503

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Book Description
Mounting failures of replication in social and biological sciences give a new urgency to critically appraising proposed reforms. This book pulls back the cover on disagreements between experts charged with restoring integrity to science. It denies two pervasive views of the role of probability in inference: to assign degrees of belief, and to control error rates in a long run. If statistical consumers are unaware of assumptions behind rival evidence reforms, they can't scrutinize the consequences that affect them (in personalized medicine, psychology, etc.). The book sets sail with a simple tool: if little has been done to rule out flaws in inferring a claim, then it has not passed a severe test. Many methods advocated by data experts do not stand up to severe scrutiny and are in tension with successful strategies for blocking or accounting for cherry picking and selective reporting. Through a series of excursions and exhibits, the philosophy and history of inductive inference come alive. Philosophical tools are put to work to solve problems about science and pseudoscience, induction and falsification.

Author: Stephen S. Senn
Publisher: John Wiley & Sons
ISBN: 9780470723579
Category : Medical
Languages : en
Pages : 523

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Book Description
Drug development is the process of finding and producingtherapeutically useful pharmaceuticals, turning them into safe andeffective medicine, and producing reliable information regardingthe appropriate dosage and dosing intervals. With regulatoryauthorities demanding increasingly higher standards in suchdevelopments, statistics has become an intrinsic and criticalelement in the design and conduct of drug development programmes. Statistical Issues in Drug Development presents anessential and thought provoking guide to the statistical issues andcontroversies involved in drug development. This highly readable second edition has been updated toinclude: Comprehensive coverage of the design and interpretation ofclinical trials. Expanded sections on missing data, equivalence, meta-analysisand dose finding. An examination of both Bayesian and frequentist methods. A new chapter on pharmacogenomics and expanded coverage ofpharmaco-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 betweenstatisticians and life scientists working within the pharmaceuticalindustry. The accessible and wide-ranging coverage make itessential reading for both statisticians and non-statisticiansworking in the pharmaceutical industry, regulatory bodies andmedical research institutes. There is also much to benefitundergraduate and postgraduate students whose courses include amedical statistics component.

Author: Stephen L. George
Publisher: CRC Press
ISBN: 1315354330
Category : Mathematics
Languages : en
Pages : 374

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Book Description
Cancer Clinical Trials: Current and Controversial Issues in Design and Analysis provides statisticians with an understanding of the critical challenges currently encountered in oncology trials. Well-known statisticians from academic institutions, regulatory and government agencies (such as the U.S. FDA and National Cancer Institute), and the pharmaceutical industry share their extensive experiences in cancer clinical trials and present examples taken from actual trials. The book covers topics that are often perplexing and sometimes controversial in cancer clinical trials. Most of the issues addressed are also important for clinical trials in other settings. After discussing general topics, the book focuses on aspects of early and late phase clinical trials. It also explores personalized medicine, including biomarker-based clinical trials, adaptive clinical trial designs, and dynamic treatment regimes.

Author: National Research Council
Publisher: National Academies Press
ISBN: 030918651X
Category : Medical
Languages : en
Pages : 163

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Book Description
Randomized clinical trials are the primary tool for evaluating new medical interventions. Randomization provides for a fair comparison between treatment and control groups, balancing out, on average, distributions of known and unknown factors among the participants. Unfortunately, these studies often lack a substantial percentage of data. This missing data reduces the benefit provided by the randomization and introduces potential biases in the comparison of the treatment groups. Missing data can arise for a variety of reasons, including the inability or unwillingness of participants to meet appointments for evaluation. And in some studies, some or all of data collection ceases when participants discontinue study treatment. Existing guidelines for the design and conduct of clinical trials, and the analysis of the resulting data, provide only limited advice on how to handle missing data. Thus, approaches to the analysis of data with an appreciable amount of missing values tend to be ad hoc and variable. The Prevention and Treatment of Missing Data in Clinical Trials concludes that a more principled approach to design and analysis in the presence of missing data is both needed and possible. Such an approach needs to focus on two critical elements: (1) careful design and conduct to limit the amount and impact of missing data and (2) analysis that makes full use of information on all randomized participants and is based on careful attention to the assumptions about the nature of the missing data underlying estimates of treatment effects. In addition to the highest priority recommendations, the book offers more detailed recommendations on the conduct of clinical trials and techniques for analysis of trial data.

Author: Richard Kay
Publisher: John Wiley & Sons
ISBN: 1118470974
Category : Medical
Languages : en
Pages : 370

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Book Description
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.

Author: Mark Chang
Publisher: Springer Science & Business Media
ISBN: 144199842X
Category : Medical
Languages : en
Pages : 316

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Book Description
Classic biostatistics, a branch of statistical science, has as its main focus the applications of statistics in public health, the life sciences, and the pharmaceutical industry. Modern biostatistics, beyond just a simple application of statistics, is a confluence of statistics and knowledge of multiple intertwined fields. The application demands, the advancements in computer technology, and the rapid growth of life science data (e.g., genomics data) have promoted the formation of modern biostatistics. There are at least three characteristics of modern biostatistics: (1) in-depth engagement in the application fields that require penetration of knowledge across several fields, (2) high-level complexity of data because they are longitudinal, incomplete, or latent because they are heterogeneous due to a mixture of data or experiment types, because of high-dimensionality, which may make meaningful reduction impossible, or because of extremely small or large size; and (3) dynamics, the speed of development in methodology and analyses, has to match the fast growth of data with a constantly changing face. This book is written for researchers, biostatisticians/statisticians, and scientists who are interested in quantitative analyses. The goal is to introduce modern methods in biostatistics and help researchers and students quickly grasp key concepts and methods. Many methods can solve the same problem and many problems can be solved by the same method, which becomes apparent when those topics are discussed in this single volume.