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Author: Xiaoyu Lu
Publisher:
ISBN:
Category :
Languages : en
Pages : 1110
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Book Description
In this research, two new designs in clinical trials are proposed. The first problem is a new Bayesian adaptive dose-finding design and its application in an oncology clinical trial. This design is used for phase IB studies with the biomarker as the endpoint and with the fewer patients. The second problem is another new Bayesian adaptive dose-finding design with longitudinal analysis and its application in phase II depression clinical trial. This design is best fit for phase II dosing-finding clinical trials with clinical endpoints. MTD information has been obtained before the trials. In adaptive dose-finding clinical trials, the strategy is to reduce the allocation of patients to non-informative doses and also save the trial cost. Bayesian adaptive dose finding design has the ability to utilize accumulating data obtained in real time to alter the course of the trial, thereby enabling dynamic allocation to different dosing groups and dropping of ineffective dosing group earlier. In this research, Bayesian adaptive method is used as a new and useful approach that applies to phase IB and phase II dose-finding clinical trials to evaluate safety and efficacy of the study treatment. Response model and Normal Dynamic Linear Models (NDLMs) are applied in stages 1-4. Conditional probability for each parameter in the model is derived using appropriate prior distributions. Markov Chain Monte Carlo (MCMC) method is used to do the simulation. Model parameters with meaningful prior distributions and the posterior quantities are obtained to evaluate the trial results and they help to determine the optimal dose level which can be used in later studies. Simulations are done for different scenarios in the two designs and used to validate the model. Five-thousand simulation trials are conducted to verify the repeatability of the results. The posterior probability of success for the trial is greater than 90% based on the simulation results. The results give clearer idea if one needs to go further to test new dose levels based on the thorough evaluation of the existing partial data. Compared with the other adaptive dose finding strategy, the proposed Bayesian adaptive designs are sensitive and robust to help the investigators draw conclusion as early as possible. The designs can also reduce sample size substantially which in turn leads to savings in cost and time. Continuous-time Markov model has the advantage over the traditional survival model and can be used to describe disease as a series of probable transitions between health states. This is an attractive feature since it provides the ability to describe the course of disease over time. It can also describe and estimate expected survival in clinical cohort. In this research, continuous-time Markov model is used in the time-to-event analysis in a phase II oncology trial. Six states are defined in the Markov chain which is used in time to progression analysis for 36 patients with neuroendocrine carcinoma. The transition probability matrix P is defined and used to iterate future transition and survival probabilities. The estimate from matrix analysis shows that the results are reliable and comparable with the Kaplan-Meier results.
Author: Xiaoyu Lu
Publisher:
ISBN:
Category :
Languages : en
Pages : 1110
Get Book Here
Book Description
In this research, two new designs in clinical trials are proposed. The first problem is a new Bayesian adaptive dose-finding design and its application in an oncology clinical trial. This design is used for phase IB studies with the biomarker as the endpoint and with the fewer patients. The second problem is another new Bayesian adaptive dose-finding design with longitudinal analysis and its application in phase II depression clinical trial. This design is best fit for phase II dosing-finding clinical trials with clinical endpoints. MTD information has been obtained before the trials. In adaptive dose-finding clinical trials, the strategy is to reduce the allocation of patients to non-informative doses and also save the trial cost. Bayesian adaptive dose finding design has the ability to utilize accumulating data obtained in real time to alter the course of the trial, thereby enabling dynamic allocation to different dosing groups and dropping of ineffective dosing group earlier. In this research, Bayesian adaptive method is used as a new and useful approach that applies to phase IB and phase II dose-finding clinical trials to evaluate safety and efficacy of the study treatment. Response model and Normal Dynamic Linear Models (NDLMs) are applied in stages 1-4. Conditional probability for each parameter in the model is derived using appropriate prior distributions. Markov Chain Monte Carlo (MCMC) method is used to do the simulation. Model parameters with meaningful prior distributions and the posterior quantities are obtained to evaluate the trial results and they help to determine the optimal dose level which can be used in later studies. Simulations are done for different scenarios in the two designs and used to validate the model. Five-thousand simulation trials are conducted to verify the repeatability of the results. The posterior probability of success for the trial is greater than 90% based on the simulation results. The results give clearer idea if one needs to go further to test new dose levels based on the thorough evaluation of the existing partial data. Compared with the other adaptive dose finding strategy, the proposed Bayesian adaptive designs are sensitive and robust to help the investigators draw conclusion as early as possible. The designs can also reduce sample size substantially which in turn leads to savings in cost and time. Continuous-time Markov model has the advantage over the traditional survival model and can be used to describe disease as a series of probable transitions between health states. This is an attractive feature since it provides the ability to describe the course of disease over time. It can also describe and estimate expected survival in clinical cohort. In this research, continuous-time Markov model is used in the time-to-event analysis in a phase II oncology trial. Six states are defined in the Markov chain which is used in time to progression analysis for 36 patients with neuroendocrine carcinoma. The transition probability matrix P is defined and used to iterate future transition and survival probabilities. The estimate from matrix analysis shows that the results are reliable and comparable with the Kaplan-Meier results.
Author: Scott M. Berry
Publisher: CRC Press
ISBN: 1439825513
Category : Mathematics
Languages : en
Pages : 316
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Book Description
Already popular in the analysis of medical device trials, adaptive Bayesian designs are increasingly being used in drug development for a wide variety of diseases and conditions, from Alzheimer's disease and multiple sclerosis to obesity, diabetes, hepatitis C, and HIV. Written by leading pioneers of Bayesian clinical trial designs, Bayesian Adapti
Author: Shein-Chung Chow
Publisher: CRC Press
ISBN: 1439839883
Category : Mathematics
Languages : en
Pages : 368
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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: Guosheng Yin
Publisher: John Wiley & Sons
ISBN: 1118183320
Category : Medical
Languages : en
Pages : 368
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Book Description
A balanced treatment of the theories, methodologies, and design issues involved in clinical trials using statistical methods There has been enormous interest and development in Bayesian adaptive designs, especially for early phases of clinical trials. However, for phase III trials, frequentist methods still play a dominant role through controlling type I and type II errors in the hypothesis testing framework. From practical perspectives, Clinical Trial Design: Bayesian and Frequentist Adaptive Methods provides comprehensive coverage of both Bayesian and frequentist approaches to all phases of clinical trial design. Before underpinning various adaptive methods, the book establishes an overview of the fundamentals of clinical trials as well as a comparison of Bayesian and frequentist statistics. Recognizing that clinical trial design is one of the most important and useful skills in the pharmaceutical industry, this book provides detailed discussions on a variety of statistical designs, their properties, and operating characteristics for phase I, II, and III clinical trials as well as an introduction to phase IV trials. Many practical issues and challenges arising in clinical trials are addressed. Additional topics of coverage include: Risk and benefit analysis for toxicity and efficacy trade-offs Bayesian predictive probability trial monitoring Bayesian adaptive randomization Late onset toxicity and response Dose finding in drug combination trials Targeted therapy designs The author utilizes cutting-edge clinical trial designs and statistical methods that have been employed at the world's leading medical centers as well as in the pharmaceutical industry. The software used throughout the book is freely available on the book's related website, equipping readers with the necessary tools for designing clinical trials. Clinical Trial Design is an excellent book for courses on the topic at the graduate level. The book also serves as a valuable reference for statisticians and biostatisticians in the pharmaceutical industry as well as for researchers and practitioners who design, conduct, and monitor clinical trials in their everyday work.
Author: Anthony C Atkinson
Publisher: CRC Press
ISBN: 1584886935
Category : Mathematics
Languages : en
Pages : 341
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Book Description
Randomised Response-Adaptive Designs in Clinical Trials presents methods for the randomised allocation of treatments to patients in sequential clinical trials. Emphasizing the practical application of clinical trial designs, the book is designed for medical and applied statisticians, clinicians, and statisticians in training. After introducing clinical trials in drug development, the authors assess a simple adaptive design for binary responses without covariates. They discuss randomisation and covariate balance in normally distributed responses and cover many important response-adaptive designs for binary responses. The book then develops response-adaptive designs for continuous and longitudinal responses, optimum designs with covariates, and response-adaptive designs with covariates. It also covers response-adaptive designs that are derived by optimising an objective function subject to constraints on the variance of estimated parametric functions. The concluding chapter explores future directions in the development of adaptive designs.
Author: Weili He
Publisher: Springer
ISBN: 1493911007
Category : Medical
Languages : en
Pages : 420
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Book Description
This edited volume is a definitive text on adaptive clinical trial designs from creation and customization to utilization. As this book covers the full spectrum of topics involved in the adaptive designs arena, it will serve as a valuable reference for researchers working in industry, government and academia. The target audience is anyone involved in the planning and execution of clinical trials, in particular, statisticians, clinicians, pharmacometricians, clinical operation specialists, drug supply managers, and infrastructure providers. In spite of the increased efficiency of adaptive trials in saving costs and time, ultimately getting drugs to patients sooner, their adoption in clinical development is still relatively low. One of the chief reasons is the higher complexity of adaptive design trials as compared to traditional trials. Barriers to the use of clinical trials with adaptive features include the concerns about the integrity of study design and conduct, the risk of regulatory non-acceptance, the need for an advanced infrastructure for complex randomization and clinical supply scenarios, change management for process and behavior modifications, extensive resource requirements for the planning and design of adaptive trials and the potential to relegate key decision makings to outside entities. There have been limited publications that address these practical considerations and recommend best practices and solutions. This book fills this publication gap, providing guidance on practical considerations for adaptive trial design and implementation. The book comprises three parts: Part I focuses on practical considerations from a design perspective, whereas Part II delineates practical considerations related to the implementation of adaptive trials. Putting it all together, Part III presents four illustrative case studies ranging from description and discussion of specific adaptive trial design considerations to the logistic and regulatory issues faced in trial implementation. Bringing together the expertise of leading key opinion leaders from pharmaceutical industry, academia, and regulatory agencies, this book provides a balanced and comprehensive coverage of practical considerations for adaptive trial design and implementation.
Author: Ying Yuan
Publisher: CRC Press
ISBN: 1315354225
Category : Mathematics
Languages : en
Pages : 238
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Book Description
Reliably optimizing a new treatment in humans is a critical first step in clinical evaluation since choosing a suboptimal dose or schedule may lead to failure in later trials. At the same time, if promising preclinical results do not translate into a real treatment advance, it is important to determine this quickly and terminate the clinical evaluation process to avoid wasting resources. Bayesian Designs for Phase I–II Clinical Trials describes how phase I–II designs can serve as a bridge or protective barrier between preclinical studies and large confirmatory clinical trials. It illustrates many of the severe drawbacks with conventional methods used for early-phase clinical trials and presents numerous Bayesian designs for human clinical trials of new experimental treatment regimes. Written by research leaders from the University of Texas MD Anderson Cancer Center, this book shows how Bayesian designs for early-phase clinical trials can explore, refine, and optimize new experimental treatments. It emphasizes the importance of basing decisions on both efficacy and toxicity.
Author: Mark Chang
Publisher: CRC Press
ISBN: 1482256606
Category : Mathematics
Languages : en
Pages : 689
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Book Description
Get Up to Speed on Many Types of Adaptive DesignsSince the publication of the first edition, there have been remarkable advances in the methodology and application of adaptive trials. Incorporating many of these new developments, Adaptive Design Theory and Implementation Using SAS and R, Second Edition offers a detailed framework to understand the
Author: Ying Yuan
Publisher: CRC Press
ISBN: 0429626835
Category : Medical
Languages : en
Pages : 239
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Book Description
Bayesian adaptive designs provide a critical approach to improve the efficiency and success of drug development that has been embraced by the US Food and Drug Administration (FDA). This is particularly important for early phase trials as they form the basis for the development and success of subsequent phase II and III trials. The objective of this book is to describe the state-of-the-art model-assisted designs to facilitate and accelerate the use of novel adaptive designs for early phase clinical trials. Model-assisted designs possess avant-garde features where superiority meets simplicity. Model-assisted designs enjoy exceptional performance comparable to more complicated model-based adaptive designs, yet their decision rules often can be pre-tabulated and included in the protocol—making implementation as simple as conventional algorithm-based designs. An example is the Bayesian optimal interval (BOIN) design, the first dose-finding design to receive the fit-for-purpose designation from the FDA. This designation underscores the regulatory agency's support of the use of the novel adaptive design to improve drug development. Features Represents the first book to provide comprehensive coverage of model-assisted designs for various types of dose-finding and optimization clinical trials Describes the up-to-date theory and practice for model-assisted designs Presents many practical challenges, issues, and solutions arising from early-phase clinical trials Illustrates with many real trial applications Offers numerous tips and guidance on designing dose finding and optimization trials Provides step-by-step illustrations of using software to design trials Develops a companion website (www.trialdesign.org) to provide freely available, easy-to-use software to assist learning and implementing model-assisted designs Written by internationally recognized research leaders who pioneered model-assisted designs from the University of Texas MD Anderson Cancer Center, this book shows how model-assisted designs can greatly improve the efficiency and simplify the design, conduct, and optimization of early-phase dose-finding trials. It should therefore be a very useful practical reference for biostatisticians, clinicians working in clinical trials, and drug regulatory professionals, as well as graduate students of biostatistics. Novel model-assisted designs showcase the new KISS principle: Keep it simple and smart!
Author: Sandeep Menon
Publisher: SAS Institute
ISBN: 1629600849
Category : Computers
Languages : en
Pages : 364
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Book Description
This book covers domains of modern clinical trial design: classical, group sequential, adaptive, and Bayesian methods applicable to and used in various phases of pharmaceutical development. Written for biostatisticians, pharmacometricians, clinical developers, and statistical programmers involved in the design, analysis, and interpretation of clinical trials, as well as students in graduate and postgraduate programs in statistics or biostatistics, it covers topics including: dose-response and dose-escalation designs; sequential methods to stop trials early for overwhelming efficacy, safety, or futility; Bayesian designs incorporating historical data; adaptive sample size re-estimation and randomization to allocate subjects to effective treatments; population enrichment designs. Methods are illustrated using clinical trials from diverse therapeutic areas, including dermatology, endocrinology, infectious disease, neurology, oncology and rheumatology. --
