Response Adaptive Randomization Using Surrogate and Primary Endpoints PDF Download
Are you looking for read ebook online? Search for your book and save it on your Kindle device, PC, phones or tablets. Download Response Adaptive Randomization Using Surrogate and Primary Endpoints PDF full book. Access full book title Response Adaptive Randomization Using Surrogate and Primary Endpoints by Hui Wang. Download full books in PDF and EPUB format.
Author: Hui Wang
Publisher:
ISBN:
Category :
Languages : en
Pages :
Get Book Here
Book Description
In recent years, adaptive designs in clinical trials have been attractive due to their efficiency and flexibility. Response adaptive randomization procedures in phase II or III clinical trials are proposed to appeal ethical concerns by skewing the probability of patient assignments based on the responses obtained thus far, so that more patients will be assigned to a superior treatment group. General response-adaptive randomizations usually assume that the primary endpoint can be obtained quickly after the treatment. However, in real clinical trials, the primary outcome is delayed, making it unusable for adaptation. Therefore, we utilize surrogate and primary endpoints simultaneously to adaptively assign subjects between treatment groups for clinical trials with continuous responses. We explore two types of primary endpoints commonly used in clinical tirials: normally distributed outcome and time-to-event outcome. We establish a connection between the surrogate and primary endpoints through a Bayesian model, and then update the allocation ratio based on the accumulated data. Through simulation studies, we find that our proposed response adaptive randomization is more effective in assigning patients to better treatments as compared with equal allocation randomization and standard response adaptive randomization which is solely based on the primary endpoint.
Author: Hui Wang
Publisher:
ISBN:
Category :
Languages : en
Pages :
Get Book Here
Book Description
In recent years, adaptive designs in clinical trials have been attractive due to their efficiency and flexibility. Response adaptive randomization procedures in phase II or III clinical trials are proposed to appeal ethical concerns by skewing the probability of patient assignments based on the responses obtained thus far, so that more patients will be assigned to a superior treatment group. General response-adaptive randomizations usually assume that the primary endpoint can be obtained quickly after the treatment. However, in real clinical trials, the primary outcome is delayed, making it unusable for adaptation. Therefore, we utilize surrogate and primary endpoints simultaneously to adaptively assign subjects between treatment groups for clinical trials with continuous responses. We explore two types of primary endpoints commonly used in clinical tirials: normally distributed outcome and time-to-event outcome. We establish a connection between the surrogate and primary endpoints through a Bayesian model, and then update the allocation ratio based on the accumulated data. Through simulation studies, we find that our proposed response adaptive randomization is more effective in assigning patients to better treatments as compared with equal allocation randomization and standard response adaptive randomization which is solely based on the primary endpoint.
Author: Richard Chin
Publisher: CRC Press
ISBN: 143983833X
Category : Mathematics
Languages : en
Pages : 189
Get Book Here
Book Description
Adaptive clinical trial designs, unlike traditional fixed clinical trial designs, enable modification of studies in response to the data generated in the course of the trial. This often results in studies that are substantially faster, more efficient, and more powerful. Recent developments in web-based real-time data entry and advances in statistic
Author: Feifang Hu
Publisher: John Wiley & Sons
ISBN: 0470055871
Category : Mathematics
Languages : en
Pages : 234
Get Book Here
Book Description
Presents a firm mathematical basis for the use of response-adaptive randomization procedures in practice The Theory of Response-Adaptive Randomization in Clinical Trials is the result of the authors' ten-year collaboration as well as their collaborations with other researchers in investigating the important questions regarding response-adaptive randomization in a rigorous mathematical framework. Response-adaptive allocation has a long history in biostatistics literature; however, largely due to the disastrous ECMO trial in the early 1980s, there is a general reluctance to use these procedures. This timely book represents a mathematically rigorous subdiscipline of experimental design involving randomization and answers fundamental questions, including: How does response-adaptive randomization affect power? Can standard inferential tests be applied following response-adaptive randomization? What is the effect of delayed response? Which procedure is most appropriate and how can "most appropriate" be quantified? How can heterogeneity of the patient population be incorporated? Can response-adaptive randomization be performed with more than two treatments or with continuous responses? The answers to these questions communicate a thorough understanding of the asymptotic properties of each procedure discussed, including asymptotic normality, consistency, and asymptotic variance of the induced allocation. Topical coverage includes: The relationship between power and response-adaptive randomization The general result for determining asymptotically best procedures Procedures based on urn models Procedures based on sequential estimation Implications for the practice of clinical trials Useful for graduate students in mathematics, statistics, and biostatistics as well as researchers and industrial and academic biostatisticians, this book offers a rigorous treatment of the subject in order to find the optimal procedure to use in practice.
Author: Lindsay A. Renfro
Publisher:
ISBN:
Category :
Languages : en
Pages :
Get Book Here
Book Description
Surrogate endpoints are desirable in clinical trials when primary endpoints are costly to obtain, difficult to measure, or require lengthy follow-up to observe. Despite legitimate concerns, evaluation of potentially beneficial treatments in some settings remains impossible or implausible without the use of surrogates. Furthermore, strong evidence based on a collection of trials, rather than a relationship observed within a single trial, is required to validate a surrogate endpoint for future primary use. We present a Bayesian approach to evaluating surrogacy using patient data from multiple trials with time-to-event endpoints that accounts for estimation error of treatment effects and offers greater computational stability than existing methods. Once a surrogate endpoint has been deemed valid for use in a future trial, a healthy skepticism should remain regarding its ability to reflect the true treatment effect that would have been observed on the primary endpoint. Despite the surrogate's intended role, few (if any) efforts have been made to formalize existing knowledge and uncertainty in the design of such a trial. We propose a Bayesian adaptive design that uses the validated surrogate as the primary endpoint, while acknowledging that this endpoint is really a surrogate, and perhaps only a recently- validated one. At prospectively-defined checkpoints, we assess the performance of the surrogate and decide whether to continue its use or switch consideration to the primary endpoint. Furthermore, our design incorporates other favorable aspects of Bayesian adaptive trials, including the ability to stop a trial early for treatment efficacy, inferiority, or trial futility. Flowgraphs are useful for modeling diseases that are well-described by multi- state models, but for which Markov assumptions are inadequate and returns to previous states are possible. Furthermore, censoring and covariates may influence the distribution of waiting times between any two states, and to a differing degree for separate transitions within the same system. We discuss the construction and advantages of flowgraph models when used to describe cancer progression within two clinical trials, where our goal is improved modeling of treatment effects and prediction of patient outcomes for the purpose of more realistic surrogacy evaluation.
Author: Shein-Chung Chow
Publisher: CRC Press
ISBN: 1439839883
Category : Mathematics
Languages : en
Pages : 368
Get Book Here
Book Description
With new statistical and scientific issues arising in adaptive clinical trial design, including the U.S. FDA's recent draft guidance, a new edition of one of the first books on the topic is needed. Adaptive Design Methods in Clinical Trials, Second Edition reflects recent developments and regulatory positions on the use of adaptive designs in clini
Author: Lanju Zhang
Publisher:
ISBN:
Category :
Languages : en
Pages : 244
Get Book Here
Book Description
Author: Narayanaswamy Balakrishnan
Publisher: John Wiley & Sons
ISBN: 9781118304761
Category : Medical
Languages : en
Pages : 0
Get Book Here
Book Description
Methods and Applications of Statistics in Clinical Trials, Volume 2: Planning, Analysis, and Inferential Methods includes updates of established literature from the Wiley Encyclopedia of Clinical Trials as well as original material based on the latest developments in clinical trials. Prepared by a leading expert, the second volume includes numerous contributions from current prominent experts in the field of medical research. In addition, the volume features: • Multiple new articles exploring emerging topics, such as evaluation methods with threshold, empirical likelihood methods, nonparametric ROC analysis, over- and under-dispersed models, and multi-armed bandit problems • Up-to-date research on the Cox proportional hazard model, frailty models, trial reports, intrarater reliability, conditional power, and the kappa index • Key qualitative issues including cost-effectiveness analysis, publication bias, and regulatory issues, which are crucial to the planning and data management of clinical trials
Author: Geert Molenberghs
Publisher: Springer Science & Business Media
ISBN: 9780387202778
Category : Mathematics
Languages : en
Pages : 440
Get Book Here
Book Description
Covers the latest research on a sensitive and controversial topic in a professional and well researched manner. Provides practical outlook as well as model guidelines and software tools that should be of interest to people who use the software tools described and those who do not. Related title by Co-author Geert Molenbergh has sold more than 3500 copies world wide. Provides dual viewpoints: from scientists in the industry as well as regulatory authorities.
Author: National Research Council
Publisher: National Academies Press
ISBN: 030918651X
Category : Medical
Languages : en
Pages : 163
Get Book Here
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: Steven Piantadosi
Publisher: Springer Nature
ISBN: 3319526367
Category : Medical
Languages : en
Pages : 2573
Get Book Here
Book Description
This is a comprehensive major reference work for our SpringerReference program covering clinical trials. Although the core of the Work will focus on the design, analysis, and interpretation of scientific data from clinical trials, a broad spectrum of clinical trial application areas will be covered in detail. This is an important time to develop such a Work, as drug safety and efficacy emphasizes the Clinical Trials process. Because of an immense and growing international disease burden, pharmaceutical and biotechnology companies continue to develop new drugs. Clinical trials have also become extremely globalized in the past 15 years, with over 225,000 international trials ongoing at this point in time. Principles in Practice of Clinical Trials is truly an interdisciplinary that will be divided into the following areas: 1) Clinical Trials Basic Perspectives 2) Regulation and Oversight 3) Basic Trial Designs 4) Advanced Trial Designs 5) Analysis 6) Trial Publication 7) Topics Related Specific Populations and Legal Aspects of Clinical Trials The Work is designed to be comprised of 175 chapters and approximately 2500 pages. The Work will be oriented like many of our SpringerReference Handbooks, presenting detailed and comprehensive expository chapters on broad subjects. The Editors are major figures in the field of clinical trials, and both have written textbooks on the topic. There will also be a slate of 7-8 renowned associate editors that will edit individual sections of the Reference.
