Sequential Experimentation In Clinical Trials PDF Download
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Author | : Jay Bartroff |
Publisher | : Springer Science & Business Media |
Total Pages | : 250 |
Release | : 2012-12-12 |
Genre | : Medical |
ISBN | : 1461461146 |
Download Sequential Experimentation in Clinical Trials Book in PDF, ePub and Kindle
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 | : P. Armitage |
Publisher | : John Wiley & Sons |
Total Pages | : 216 |
Release | : 1975 |
Genre | : Medical |
ISBN | : |
Download Sequential Medical Trials Book in PDF, ePub and Kindle
Author | : Christopher Jennison |
Publisher | : CRC Press |
Total Pages | : 416 |
Release | : 1999-09-15 |
Genre | : Mathematics |
ISBN | : 9781584888581 |
Download Group Sequential Methods with Applications to Clinical Trials Book in PDF, ePub and Kindle
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 | : Toshimitsu Hamasaki |
Publisher | : Springer |
Total Pages | : 118 |
Release | : 2016-06-01 |
Genre | : Mathematics |
ISBN | : 4431559000 |
Download Group-Sequential Clinical Trials with Multiple Co-Objectives Book in PDF, ePub and Kindle
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 | : John Whitehead |
Publisher | : John Wiley & Sons |
Total Pages | : 342 |
Release | : 1997-08-04 |
Genre | : Science |
ISBN | : 9780471975502 |
Download The Design and Analysis of Sequential Clinical Trials Book in PDF, ePub and Kindle
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. Emphasis is placed on the triangular test and other procedures based on straight line stopping boundaries. These methods allow for frequent or occasional interim analyses and permit the analysis of a wide variety of patient responses. Alternative procedures are also covered in detail, and these include -spending function methods, repeated confidence intervals and Bayesian approaches to sequential clinical trials.
Author | : Haipeng Xing |
Publisher | : Intl Food Policy Res Inst |
Total Pages | : 28 |
Release | : 2013-06-26 |
Genre | : Social Science |
ISBN | : |
Download The Logic of Adaptive Sequential Experimentation in Policy Design Book in PDF, ePub and Kindle
Inspired by the wide adoption of rigorous randomized controlled trials (RCTs) in medical research, economists and other social scientists have increasingly used RCTs in their research. As researchers pick up projects amenable to the RCT methodology, they likely leave out important questions to which RCTs cannot be directly applied. As a result, RCTs have been criticized for the proclivity of addressing trivial questions. As a matter of fact, in medical research RCTs are an integral part of adaptive sequential experiment designa few steps must be taken to screen out drugs that have toxins and strong side effects before running any RCTs on humans. In this paper, we argue that economists can learn a great deal from the design principles implemented in medical research. We develop a theoretical model to show the logic of adaptive sequential experiment design in the presence of uncertainty over negative effects and discuss how to choose samples in a population to minimize the experiment cost. We also point out the applications of our proposed framework in the economic domain, such as economic reforms and new product design.
Author | : David Harrington |
Publisher | : Springer Science & Business Media |
Total Pages | : 213 |
Release | : 2011-10-09 |
Genre | : Medical |
ISBN | : 1461401402 |
Download Designs for Clinical Trials Book in PDF, ePub and Kindle
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 | : Tian Zhao |
Publisher | : |
Total Pages | : 188 |
Release | : 2015 |
Genre | : Biometry |
ISBN | : |
Download Multiple Comparisons in Truncated Group Sequential Experiments with Applications in Clinical Trials Book in PDF, ePub and Kindle
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.
Author | : Joseph L. Fleiss |
Publisher | : John Wiley & Sons |
Total Pages | : 458 |
Release | : 2011-01-25 |
Genre | : Mathematics |
ISBN | : 1118031172 |
Download Design and Analysis of Clinical Experiments Book in PDF, ePub and Kindle
First published in 1986, this unique reference to clinical experimentation remains just as relevant today. Focusing on the principles of design and analysis of studies on human subjects, this book utilizes and integrates both modern and classical designs. Coverage is limited to experimental comparisons of treatments, or in other words, clinical studies in which treatments are assigned to subjects at random.
Author | : Timothy Michael Skalland |
Publisher | : |
Total Pages | : 90 |
Release | : 2015 |
Genre | : Clinical trials |
ISBN | : |
Download An Evaluation of Design and Inference in Special Topics of Group Sequential Procedures Book in PDF, ePub and Kindle
Randomized trials are the gold standard for the clinical assessment of a new treatment compared to a placebo or standard of care. Often in clinical trials, patients are accrued sequentially rather than all at once. Thus, the data from such a trial becomes available sequentially to the researcher. Monitoring and testing the accrued data throughout a trial and making decisions based on on such tests that could terminate the trial early is called sequential testing. Designing and analyzing such sequential trials has garnered much attention in the statistical literature over the last 50+ years. The added flexibility and benefi ts from such a trial do not come free-of-cost. Careful considerations in the design, careful monitoring of the data throughout, and careful analysis of the data at the conclusion are necessary to preserve the integrity of such a sequential clinical trial. This thesis will be mostly concerned with a special form of sequential testing called a group sequential procedure. Such procedures have the benefi t of a reduction in expected sample size while not being burdened by continual monitoring of the data after every observation. Special topics of group sequential procedures include the concepts of overrun, secondary endpoints and adaptive group sequential procedures. Overrun is the accrual of data after the decision to terminate the trial has been reached. We investigate and compare popular approaches to the incorporation of such data into the final analysis. Through a simulation study, it is found that a random weighting of the p-values from the data up to the termination of the trial and the overrun data based the sample sizes for such data under the Sample Mean Ordering of the outcome space leads to the shortest average con fidence intervals while maintaining the nominal coverage probability. Most clinical trials are designed and evaluated using a primary endpoint for the treatment eff ect. Some trials have secondary endpoints to assess either safety or additional clinical benefi ts beyond the primary outcome. We consider the design and analysis of group sequential trials when both a primary and secondary endpoint are of interest. Our investigations are done in the setting of a gatekeeping procedure. We are able to unify and generalize global proofs to certain propositions made by other researchers when we consider testing both a primary and secondary endpoint. We further investigate secondary inference in the form of con fidence interval construction through an extensive simulation study. We find that the approach of Whitehead et al. (2000) outperforms existing methods for the settings considered. Adaptive clinical trials seek to modify some aspect of the trial after an interim look at the data in order to improve the odds of a successful trial by the end. We compare some popular choices of adaptive Phase II two-stage designs and introduce a new design while evaluating operating characteristics (Type I error, Type II error and expected sample sizes). Majority of the literature focuses on minimizing the expected sample size under the null hypothesis only. Our new Quasi-Symmetric n2-design seeks to substantially reduce the expected sample size under the parameter values close to the design alternative while minimally increasing expected sample size under the design null. We evaluate and compare such a design to existing methods.