Multiple Comparisons in Truncated Group Sequential Experiments with Applications in Clinical Trials

Multiple Comparisons in Truncated Group Sequential Experiments with Applications in Clinical Trials
Author: Tian Zhao
Publisher:
Total Pages: 188
Release: 2015
Genre: Biometry
ISBN:

With the rapid growth of the pharmaceutical industry, it became particularly important to develop efficient statistical techniques for conducting clinical trials. Practically clinical trials nowadays are conducted to answer many questions rather than exploring just one hypothesis. A treatment has to pass the efficacy and safety standards minimally. Handling multiplicity in clinical trials has become a hot topic. During the last two decades, a number of new statistical techniques appeared that improved the overall power of multiple testing procedures while still controlling the familywise Type I error rate. However, a large portion of modern clinical trials is conducted sequentially. The last five years or so, Bartroff and Lai, De and Baron, applied stepwise testing of multiple hypotheses. The procedures were open-ended. But the standard practice requires any clinical trials to be completed by the given date. Any stopping rules have to be truncated. This is the main difference in the problem considered in this dissertation from all the previously proposed methods. In this dissertation, we derived the simultaneous testing of multiple hypotheses that: - control the familywise Type I and Type II error rates; - terminate sampling with probability one at or before the given number of sampled groups; - optimize the expected sample size. For the purpose of testing multiple hypotheses, with a given truncation point, we developed a new group sequential procedure based on the truncated sequential probability ratio test. Our method resulted in an improved single-hypothesis testing that appeared to be more efficient than Pollock's method proposed earlier for the same problem. Extending this to multiple hypotheses by means of Holm-Bonferroni stepwise approach, we derive a truncated group sequential procedure for the simultaneous testing of multiple hypotheses that controls familywise Type I and Type II errors in the strong sense. The new methods can be applied to any truncated sequential sampling for multiple comparisons. Optimizing the expected sampling cost of a clinical trial in this context inevitably implies reduction in the cost of medical treatments, and therefore, it ultimately results in the reduced cost of health care.

Group Sequential Methods with Applications to Clinical Trials

Group Sequential Methods with Applications to Clinical Trials
Author: Christopher Jennison
Publisher: CRC Press
Total Pages: 416
Release: 1999-09-15
Genre: Mathematics
ISBN: 9781584888581

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.

Multiple Testing Problems in Pharmaceutical Statistics

Multiple Testing Problems in Pharmaceutical Statistics
Author: Alex Dmitrienko
Publisher: CRC Press
Total Pages: 323
Release: 2009-12-08
Genre: Mathematics
ISBN: 1584889853

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

Group-Sequential Clinical Trials with Multiple Co-Objectives

Group-Sequential Clinical Trials with Multiple Co-Objectives
Author: Toshimitsu Hamasaki
Publisher: Springer
Total Pages: 118
Release: 2016-06-01
Genre: Mathematics
ISBN: 4431559000

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.

Applied Sequential Methodologies

Applied Sequential Methodologies
Author: Nitis Mukhopadhyay
Publisher: CRC Press
Total Pages: 498
Release: 2004-01-28
Genre: Mathematics
ISBN: 9780824753955

A technically precise yet clear presentation of modern sequential methodologies having immediate applications to practical problems in the real world, Applied Sequential Methodologies communicates invaluable techniques for data mining, agricultural science, genetics, computer simulation, finance, clinical trials, sonar signal detection, randomization, multiple comparisons, psychology, tracking, surveillance, and numerous additional areas of application. Includes more than 500 references, 165 figures and tables, and over 25 pages of subject and author indexes. Applied Sequential Methodologies brings the crucial nature of sequential approaches up to speed with recent theoretical gains, demonstrating their utility for solving real-life problems associated with Change-point detection in multichannel and distributed systems Best component selection for multivariate distributions Multistate processes Approximations for moving sums of discrete random variables Interim and terminal analyses of clinical trials Adaptive designs for longitudinal clinical trials Slope estimation in measurement-error models Tests for randomization and target tracking Appropriate count of simulation runs Stock price models Orders of genes Size and power control in multiple comparisons Authored by 33 leading scientists, this volume will greatly benefit sequential analysts, data analysts, applied statisticians, biometricians, clinical trialists, and upper-level undergraduate and graduate students in these disciplines.

Multiple Comparisons Using R

Multiple Comparisons Using R
Author: Frank Bretz
Publisher: CRC Press
Total Pages: 202
Release: 2016-04-19
Genre: Mathematics
ISBN: 1420010905

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.

Handbook of Multiple Comparisons

Handbook of Multiple Comparisons
Author: Xinping Cui
Publisher: CRC Press
Total Pages: 418
Release: 2021-11-18
Genre: Mathematics
ISBN: 0429633882

Written by experts that include originators of some key ideas, chapters in the Handbook of Multiple Testing cover multiple comparison problems big and small, with guidance toward error rate control and insights on how principles developed earlier can be applied to current and emerging problems. Some highlights of the coverages are as follows. Error rate control is useful for controlling the incorrect decision rate. Chapter 1 introduces Tukey's original multiple comparison error rates and point to how they have been applied and adapted to modern multiple comparison problems as discussed in the later chapters. Principles endure. While the closed testing principle is more familiar, Chapter 4 shows the partitioning principle can derive confidence sets for multiple tests, which may become important as the profession goes beyond making decisions based on p-values. Multiple comparisons of treatment efficacy often involve multiple doses and endpoints. Chapter 12 on multiple endpoints explains how different choices of endpoint types lead to different multiplicity adjustment strategies, while Chapter 11 on the MCP-Mod approach is particularly useful for dose-finding. To assess efficacy in clinical trials with multiple doses and multiple endpoints, the reader can see the traditional approach in Chapter 2, the Graphical approach in Chapter 5, and the multivariate approach in Chapter 3. Personalized/precision medicine based on targeted therapies, already a reality, naturally leads to analysis of efficacy in subgroups. Chapter 13 draws attention to subtle logical issues in inferences on subgroups and their mixtures, with a principled solution that resolves these issues. This chapter has implication toward meeting the ICHE9R1 Estimands requirement. Besides the mere multiple testing methodology itself, the handbook also covers related topics like the statistical task of model selection in Chapter 7 or the estimation of the proportion of true null hypotheses (or, in other words, the signal prevalence) in Chapter 8. It also contains decision-theoretic considerations regarding the admissibility of multiple tests in Chapter 6. The issue of selected inference is addressed in Chapter 9. Comparison of responses can involve millions of voxels in medical imaging or SNPs in genome-wide association studies (GWAS). Chapter 14 and Chapter 15 provide state of the art methods for large scale simultaneous inference in these settings.

Analysis of Clinical Trials Using SAS

Analysis of Clinical Trials Using SAS
Author: Alex Dmitrienko
Publisher: SAS Institute
Total Pages: 455
Release: 2017-07-17
Genre: Computers
ISBN: 1635261449

Analysis of Clinical Trials Using SAS®: A Practical Guide, Second Edition bridges the gap between modern statistical methodology and real-world clinical trial applications. Tutorial material and step-by-step instructions illustrated with examples from actual trials serve to define relevant statistical approaches, describe their clinical trial applications, and implement the approaches rapidly and efficiently using the power of SAS. Topics reflect the International Conference on Harmonization (ICH) guidelines for the pharmaceutical industry and address important statistical problems encountered in clinical trials. Commonly used methods are covered, including dose-escalation and dose-finding methods that are applied in Phase I and Phase II clinical trials, as well as important trial designs and analysis strategies that are employed in Phase II and Phase III clinical trials, such as multiplicity adjustment, data monitoring, and methods for handling incomplete data. This book also features recommendations from clinical trial experts and a discussion of relevant regulatory guidelines. This new edition includes more examples and case studies, new approaches for addressing statistical problems, and the following new technological updates: SAS procedures used in group sequential trials (PROC SEQDESIGN and PROC SEQTEST) SAS procedures used in repeated measures analysis (PROC GLIMMIX and PROC GEE) macros for implementing a broad range of randomization-based methods in clinical trials, performing complex multiplicity adjustments, and investigating the design and analysis of early phase trials (Phase I dose-escalation trials and Phase II dose-finding trials) Clinical statisticians, research scientists, and graduate students in biostatistics will greatly benefit from the decades of clinical research experience and the ready-to-use SAS macros compiled in this book.

Handbook of Sequential Analysis

Handbook of Sequential Analysis
Author: B.K. Ghosh
Publisher: CRC Press
Total Pages: 672
Release: 1991-04-24
Genre: Mathematics
ISBN: 9780824784089

Sequential analysis refers to the body of statistical theory and methods where the sample size may depend in a random manner on the accumulating data. A formal theory in which optimal tests are derived for simple statistical hypotheses in such a framework was developed by Abraham Wald in the early 1