Download or read book Single Arm Phase II Survival Trial Design written by Jianrong Wu and published by CRC Press. This book was released on 2021-07-19 with total page 273 pages. Available in PDF, EPUB and Kindle. Book excerpt: Single-Arm Phase II Survival Trial Design provides a comprehensive summary to the most commonly- used methods for single-arm phase II trial design with time-to-event endpoints. Single-arm phase II trials are a key component for successfully developing advanced cancer drugs and treatments, particular for target therapy and immunotherapy in which time-to-event endpoints are often the primary endpoints. Most test statistics for single-arm phase II trial design with time-to-event endpoints are not available in commercial software. Key Features: Covers the most frequently used methods for single-arm phase II trial design with time-to-event endpoints in a comprehensive fashion. Provides new material on phase II immunotherapy trial design and phase II trial design with TTP ratio endpoint. Illustrates trial designs by real clinical trial examples Includes R code for all methods proposed in the book, enabling straightforward sample size calculation.

Download or read book Single Arm Phase II Survival Trial Design written by Jianrong Wu and published by CRC Press. This book was released on 2021-08-06 with total page 225 pages. Available in PDF, EPUB and Kindle. Book excerpt: Single-Arm Phase II Survival Trial Design provides a comprehensive summary to the most commonly- used methods for single-arm phase II trial design with time-to-event endpoints. Single-arm phase II trials are a key component for successfully developing advanced cancer drugs and treatments, particular for target therapy and immunotherapy in which time-to-event endpoints are often the primary endpoints. Most test statistics for single-arm phase II trial design with time-to-event endpoints are not available in commercial software. Key Features: Covers the most frequently used methods for single-arm phase II trial design with time-to-event endpoints in a comprehensive fashion. Provides new material on phase II immunotherapy trial design and phase II trial design with TTP ratio endpoint. Illustrates trial designs by real clinical trial examples Includes R code for all methods proposed in the book, enabling straightforward sample size calculation.

Download or read book Randomized Phase II Cancer Clinical Trials written by Sin-Ho Jung and published by CRC Press. This book was released on 2013-05-02 with total page 250 pages. Available in PDF, EPUB and Kindle. Book excerpt: In cancer research, a traditional phase II trial is designed as a single-arm trial that compares the experimental therapy to a historical control. This simple trial design has led to several adverse issues, including increased false positivity of phase II trial results and negative phase III trials. To rectify these problems, oncologists and biostatisticians have begun to use a randomized phase II trial that compares an experimental therapy with a prospective control therapy. Randomized Phase II Cancer Clinical Trials explains how to properly select and accurately use diverse statistical methods for designing and analyzing phase II trials. The author first reviews the statistical methods for single-arm phase II trials since some methodologies for randomized phase II trials stem from single-arm phase II trials and many phase II cancer clinical trials still use single-arm designs. The book then presents methods for randomized phase II trials and describes statistical methods for both single-arm and randomized phase II trials. Although the text focuses on phase II cancer clinical trials, the statistical methods covered can also be used (with minor modifications) in phase II trials for other diseases and in phase III cancer clinical trials. Suitable for cancer clinicians and biostatisticians, this book shows how randomized phase II trials with a prospective control resolve the shortcomings of traditional single-arm phase II trials. It provides readers with numerous statistical design and analysis methods for randomized phase II trials in oncology.

Download or read book Statistical Methods for Survival Trial Design written by Jianrong Wu and published by CRC Press. This book was released on 2018-06-14 with total page 243 pages. Available in PDF, EPUB and Kindle. Book excerpt: Statistical Methods for Survival Trial Design: With Applications to Cancer Clinical Trials Using R provides a thorough presentation of the principles of designing and monitoring cancer clinical trials in which time-to-event is the primary endpoint. Traditional cancer trial designs with time-to-event endpoints are often limited to the exponential model or proportional hazards model. In practice, however, those model assumptions may not be satisfied for long-term survival trials. This book is the first to cover comprehensively the many newly developed methodologies for survival trial design, including trial design under the Weibull survival models; extensions of the sample size calculations under the proportional hazard models; and trial design under mixture cure models, complex survival models, Cox regression models, and competing-risk models. A general sequential procedure based on the sequential conditional probability ratio test is also implemented for survival trial monitoring. All methodologies are presented with sufficient detail for interested researchers or graduate students.

Download or read book Small Clinical Trials written by Institute of Medicine and published by National Academies Press. This book was released on 2001-01-01 with total page 221 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Two stage Design for Phase II Cancer Clinical Trials with Multiple Endpoints written by Hui Gu and published by . This book was released on 2017 with total page 110 pages. Available in PDF, EPUB and Kindle. Book excerpt: The main purpose of a single-arm phase II cancer trial of a new regimen is to determine whether it has sufficient anti-tumor activity against a specific type of tumor to warrant its further clinical development. Such a research question can be answered under the frame- work of hypothesis testing. With the advent of targeted therapies that prolong disease stabilization, cancer patients typically experience stable disease (SD) rather than tumor shrinkage. It has been shown that patients with SD also achieve clinical benefits. There- fore, when evaluating the anti-tumor activity of a new treatment, clinicians are interested not only in overall response rate (complete or partial response(s)), but also in other types of measurements indicating clinical benefit. Taking two primary efficacy endpoints as an example, if the new treatment can improve on either endpoint(s), it may be promising for further evaluation. Therefore, "OR" logical relationship between the two primary efficacy endpoints is used when specifying the alternative hypothesis. In phase II cancer clinical trials, two-stage designs rather than single-stage ones are widely used for its possibility of early termination for futility to protect cancer patients. Motivated by two real cancer clinical trials, we propose a single-arm two-stage phase II cancer clinical trial design with two dichotomous alternative primary efficacy endpoints. Because of unknown correlation between two endpoints at the design stage, minimax rule is used to determine the optimal design, which minimizes the maximum of the expected sample size among all possible correlations, subject to the type I and II error constraints. Optimal designs for a variety of design parameters as well as the corresponding operating characteristics are provided. In addition, the statistical inferences of the design are studied. The MLE point estimators as well as confidence regions for the true event rates for the two efficacy endpoints are derived. Three types of confidence regions are obtained by inverting likelihood based test statistics: Wald, Score, and Likelihood ratio statistics. Among the three, the likelihood ratio-type confidence region performs the best in terms of good coverage probability and comparable expected area, and thus is recommended for this two-endpoint two-stage design.

Download or read book Group Sequential Methods with Applications to Clinical Trials written by Christopher Jennison and published by CRC Press. This book was released on 1999-09-15 with total page 416 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Design and Inference in Phase II III Clinical Trials Incorporating Monitoring of Multiple Endpoints written by Herman E. Ray and published by . This book was released on 2011 with total page 200 pages. Available in PDF, EPUB and Kindle. Book excerpt: The phase II clinical trial is a critical step in the drug development process. In the oncology setting, phase II studies typically evaluate one primary endpoint, which is efficacy. In practice, a binary measurement representing the response to the new treatment defines the efficacy. The single-arm, multiple-stage designs are popular and the Simon 2-Stage design is preferred. Although the study designs evaluate the efficacy, the subject's safety is an important concern. Safety is monitored through the number of grade 3 or grade 4 toxic events. The phase II clinical trial design based on the primary endpoint is typically augmented with an ad hoc monitoring rule. The studies are designed in two steps. First, the sample size and critical values are determined based on the primary endpoint. Then an ad hoc toxicity monitoring rule is applied to the study. Previous authors recommended a method to monitor toxic events after each patient is enrolled which is also known as continuous toxicity monitoring. A trial designed at the JG Brown Cancer Center combined the Simon 2-Stage design with continuous toxicity monitoring. We describe how to integrate the continuous toxicity monitoring methodology with the Simon 2-Stage design for response. Theoretical justification is given for the nominal size, power, probability of early termination (PET), and average sample size (ASN) of the combined testing procedure. A series of simulations were conducted to investigate the performance of the combined procedure. We discover that the type I error rate, type II error rate, PET, and ASN are subject to the correlation between toxicity and response. In fact, the study may have a smaller type I error rate than expected. The theoretical expressions derived to describe the operating characteristics of the combined procedure were utilized to create a new flexible, bivariate, multistage clinical trial. The design is considered flexible because it can monitor toxicity on a different schedule than response. An example is considered in which toxicity is measured after four equally spaced intervals and the response is evaluated only at the second and fourth toxicity examinations. This example corresponds to a data monitoring committee's meeting schedule that may happen every 6 months over a two year span. The effect of the correlation on the type I and type II error rates is examined through simulation. The simulations also examine the power over the range of response rates with a fixed toxicity rate in the alternative region and vice-versa. There are several single-arm, multiple-stage clinical trial designs that consider multiple endpoints at the same time. A subset of the designs includes those that consider both efficacy and toxicity as binary endpoints. A common problem, considered after the conduct of the trial, is appropriate inference given the repeated examinations of the multiple endpoints. We propose a uniformly minimum variance unbiased estimator (UMVUE) for the response in a multistage clinical trial design incorporating toxicity effects. The proposed estimator and the typical maximum likelihood estimator (MLE) are evaluated through simulation. The estimator requires further modification when continuous toxicity monitoring is combined with a multistage design for response. The modified estimator maintains low bias over the range of possible response values. The larger phase lIb or phase III clinical trial is the logical extension of the bivariate research based on exact calculations. The phase lIb or III clinical trials typically include an ad hoc toxicity monitoring rule ensuring participant protection. The designs also include provisions to allow early stopping for futility or efficacy utilizing group sequential theory or stochastic curtailment. We also examine a novel large sample clinical trial design that incorporates correlation between the response and toxicity events. The design uses the typical critical values associated with the standard normal distribution. It also searches for critical values specific to the global hypothesis associated with both response and toxicity. The bivariate test is then combined with efficacy and safety monitoring based on a flexible time-varying conditional power methodology. The type I and type II error rates of the bivariate test procedure, along with the bivariate test procedure combined with the conditional power methodology, are investigated through simulation. A modification is developed for the conditional power methodology to preserve the type I and type II error rates. In the end, the research extends the bivariate clinical trial designs in an attempt to make them more appealing in practice. Although, the research resulted in positive outcomes, additional work is required.

Download or read book Bayesian Designs for Phase I II Clinical Trials written by Ying Yuan and published by CRC Press. This book was released on 2017-12-19 with total page 238 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Developing a Protocol for Observational Comparative Effectiveness Research A User s Guide written by Agency for Health Care Research and Quality (U.S.) and published by Government Printing Office. This book was released on 2013-02-21 with total page 236 pages. Available in PDF, EPUB and Kindle. Book excerpt: This User’s Guide is a resource for investigators and stakeholders who develop and review observational comparative effectiveness research protocols. It explains how to (1) identify key considerations and best practices for research design; (2) build a protocol based on these standards and best practices; and (3) judge the adequacy and completeness of a protocol. Eleven chapters cover all aspects of research design, including: developing study objectives, defining and refining study questions, addressing the heterogeneity of treatment effect, characterizing exposure, selecting a comparator, defining and measuring outcomes, and identifying optimal data sources. Checklists of guidance and key considerations for protocols are provided at the end of each chapter. The User’s Guide was created by researchers affiliated with AHRQ’s Effective Health Care Program, particularly those who participated in AHRQ’s DEcIDE (Developing Evidence to Inform Decisions About Effectiveness) program. Chapters were subject to multiple internal and external independent reviews. More more information, please consult the Agency website: www.effectivehealthcare.ahrq.gov)

Download or read book Neuroscience Trials of the Future written by National Academies of Sciences, Engineering, and Medicine and published by National Academies Press. This book was released on 2016-11-07 with total page 111 pages. Available in PDF, EPUB and Kindle. Book excerpt: On March 3-4, 2016, the National Academies of Sciences, Engineering, and Medicine's Forum on Neuroscience and Nervous System Disorders held a workshop in Washington, DC, bringing together key stakeholders to discuss opportunities for improving the integrity, efficiency, and validity of clinical trials for nervous system disorders. Participants in the workshop represented a range of diverse perspectives, including individuals not normally associated with traditional clinical trials. The purpose of this workshop was to generate discussion about not only what is feasible now, but what may be possible with the implementation of cutting-edge technologies in the future.

Download or read book Bayesian Adaptive Design for Immunotherapy and Targeted Therapy written by Haitao Pan and published by Springer Nature. This book was released on 2023-04-19 with total page 267 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides a comprehensive review of novel adaptive trial designs for targeted therapies and immunotherapies. This book covers a wide range of novel statistical designs for various clinical settings, including early phase dose-escalation study, proof-of-concept trials, and confirmatory studies with registrational. The book includes real-life examples and software to facilitate practitioners to learn and use the designs in practice.

Download or read book Bayesian Adaptive Methods for Clinical Trials written by Scott M. Berry and published by CRC Press. This book was released on 2010-07-19 with total page 316 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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

Download or read book Exact Statistical Inference for Categorical Data written by Guogen Shan and published by Academic Press. This book was released on 2016-01-22 with total page 68 pages. Available in PDF, EPUB and Kindle. Book excerpt: Exact Statistical Inference for Categorical Data discusses the way asymptotic approaches have been often used in practice to make statistical inference. This book introduces both conditional and unconditional exact approaches for the data in 2 by 2, or 2 by k contingency tables, and is an ideal reference for users who are interested in having the convenience of applying asymptotic approaches, with less computational time. In addition to the existing conditional exact inference, some efficient, unconditional exact approaches could be used in data analysis to improve the performance of the testing procedure. Demonstrates how exact inference can be used to analyze data in 2 by 2 tables Discusses the analysis of data in 2 by k tables using exact inference Explains how exact inference can be used in genetics

Download or read book A National Cancer Clinical Trials System for the 21st Century written by Institute of Medicine and published by National Academies Press. This book was released on 2010-07-08 with total page 317 pages. Available in PDF, EPUB and Kindle. Book excerpt: The National Cancer Institute's (NCI) Clinical Trials Cooperative Group Program has played a key role in developing new and improved cancer therapies. However, the program is falling short of its potential, and the IOM recommends changes that aim to transform the Cooperative Group Program into a dynamic system that efficiently responds to emerging scientific knowledge; involves broad cooperation of stakeholders; and leverages evolving technologies to provide high-quality, practice-changing research.

Download or read book Oncology Clinical Trials written by William Kevin Kelly, DO and published by Springer Publishing Company. This book was released on 2018-03-28 with total page 600 pages. Available in PDF, EPUB and Kindle. Book excerpt: The second edition of Oncology Clinical Trials has been thoroughly revised and updated and now contains the latest designs and methods of conducting and analyzing cancer clinical trials in the era of precision medicine with biologic agents—including trials investigating the safety and efficacy of targeted therapies, immunotherapies, and combination therapies as well as novel radiation therapy modalities. Now divided into six sections this revamped book provides the necessary background and expert guidance from the principles governing oncology clinical trials to the innovative statistical design methods permeating the field; from conducting trials in a safe and effective manner, analyzing and interpreting the data, to a forward-looking assessment and discussion of regulatory issues impacting domestic, international, and global clinical trials. Considered by many as the gold standard reference on oncology clinical trials in the field, the second edition continues to provide examples of real-life flaws and real-world examples for how to successfully design, conduct and analyze quality clinical trials and interpret them. With chapters written by oncologists, researchers, biostatisticians, clinical research administrators, and industry and FDA representatives, this volume provides a comprehensive guide in the design, conduct, monitoring, analysis, and reporting of clinical trials in oncology. NEW TO THIS EDITION: Outlines how to design clinical trials with and without biomarker testing—including genomics-based “basket” trials, and adaptive trials for all phases during treatment and quality-of-life trials Includes new chapters on immunotherapy trials, radiation therapy trials, multi-arm trials, meta-analysis and adaptive design, use of genomics, dose modifications and use of ancillary treatments in investigational studies, establishing surrogate endpoints, practical issues with correlative studies, cost-effectiveness analysis, and more Comprehensively covers all regulatory aspects in the pursuit of global oncology trials Digital access to the ebook included

Download or read book Textbook of Clinical Trials in Oncology written by Susan Halabi and published by CRC Press. This book was released on 2019-04-24 with total page 626 pages. Available in PDF, EPUB and Kindle. Book excerpt: There is an increasing need for educational resources for statisticians and investigators. Reflecting this, the goal of this book is to provide readers with a sound foundation in the statistical design, conduct, and analysis of clinical trials. Furthermore, it is intended as a guide for statisticians and investigators with minimal clinical trial experience who are interested in pursuing a career in this area. The advancement in genetic and molecular technologies have revolutionized drug development. In recent years, clinical trials have become increasingly sophisticated as they incorporate genomic studies, and efficient designs (such as basket and umbrella trials) have permeated the field. This book offers the requisite background and expert guidance for the innovative statistical design and analysis of clinical trials in oncology. Key Features: Cutting-edge topics with appropriate technical background Built around case studies which give the work a "hands-on" approach Real examples of flaws in previously reported clinical trials and how to avoid them Access to statistical code on the book’s website Chapters written by internationally recognized statisticians from academia and pharmaceutical companies Carefully edited to ensure consistency in style, level, and approach Topics covered include innovating phase I and II designs, trials in immune-oncology and rare diseases, among many others