Download or read book Evaluation of Strategies for the Phase II to Phase III Progression in Treatment Discovery written by Brittany J. Sanchez and published by . This book was released on 2014 with total page 112 pages. Available in PDF, EPUB and Kindle. Book excerpt: The goal of clinical research is to improve the health of the population through the prevention, diagnosis, and treatment of disease. Clinical trials are essential for reliably evaluating a proposed treatment to determine whether it should be adopted into clinical practice. Current standards involve the evaluation of a new treatment through several phases of investigation. After preliminary evaluations of the safety and ethics of further study, promising treatments are studied in preliminary screening trials and then ultimately large, confirmatory trials. Although well developed, the "treatment discovery process" is lengthy, expensive, and has low success rates for treatments even at confirmatory phases of the investigation. Improvements to trial design and implementation are necessary for better achieving the goals of clinical research. In this research, we consider the progression of studies for investigating a new treatment, and discuss strategies in a framework that encompasses the period from the start of preliminary Phase II studies to the completion of the confirmatory Phase III studies. Using a general notational framework for evaluating new treatments, we examine optimality criteria for a strategy that best addresses the often competing goals of science, ethics, and efficiency. These optimality criteria include not only the standard frequentest operating characteristics of type I error and power and the standard Bayesian criteria of positive and negative predictive values, but also the efficiency considerations of the number of new treatments identified in a setting with limited resources. We parameterize the Phase II and Phase III designs using frequentest type I error and power in such a way as to attain high Bayesian positive predictive value (PPV). We then explore the impact specific choices of those design parameters have on the number of effective and ineffective treatments identified with constrained resources. We illustrate how allowing for early trial termination for efficacy or futility with a group sequential design (GSD) within Phase II and/or Phase III improves efficiency in terms of the number of subjects used on average for identifying effective therapies. Other methods for improving efficiency by eliminating the time spent between Phase II and Phase III have been proposed. A "seamless" Phase II/III trial design is one that combines the Phase II screening stage with the Phase III confirmatory stage. We consider how a single sequential design differs from the optimal approach of independent stages. We then explore how the traditional approach of adapting hypotheses at the end of Phase II fits in with the newer adaptive methods. We discuss how powering of Phase III based on Phase II results mimics adaptive sample size re-estimation / re-powering of study and does not offer improvement beyond that of GSDs. Bias in the estimate of the treatment effect is a result of the lack of precision of small samples inherent in Phase II studies and at early interim analyses. We investigate how such bias can be addressed with adjustment methods. We then examine differences between conducting subgroup analyses when there exist homogeneous versus heterogeneous effects and how inflation of the type I error can be controlled in this setting and in the setting of considering multiple summary measures. In our research, we thus demonstrate that the optimal Phase II to Phase III progression defined by an acceptable PPV and a maximal number of effective treatments can be identified for an anticipated prevalence and hypothesized resources by a parameterization of type I error and power at Phase II. We recognize that several approaches lead to the same optimality criteria, and that the chosen strategy will depend on individual objectives of clinical researchers, trial sponsors, regulatory agencies, patients on study, and those who might benefit from new knowledge about treatments being studied.
Download or read book The Prevention and Treatment of Missing Data in Clinical Trials written by National Research Council and published by National Academies Press. This book was released on 2010-12-21 with total page 163 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Frontiers in Anti Cancer Drug Discovery written by Atta-ur-Rahman and published by Bentham Science Publishers. This book was released on 2014-09-15 with total page 413 pages. Available in PDF, EPUB and Kindle. Book excerpt: Frontiers in Anti-Cancer Drug Discovery is an Ebook series devoted to publishing the latest and the most important advances in Anti-Cancer drug design and discovery. Eminent scientists write contributions on all areas of rational drug design and drug discovery, including medicinal chemistry, in-silico drug design, combinatorial chemistry, high-throughput screening, drug targets, recent important patents, and structure-activity relationships. The Ebook series should prove to be of interest to all pharmaceutical scientists involved in research in Anti-Cancer drug design and discovery. Each volume is devoted to the major advances in Anti-Cancer drug design and discovery. The Ebook series is essential reading for all scientists involved in drug design and discovery who wish to keep abreast of rapid and important developments in the field.
Download or read book Rare Diseases and Orphan Products written by Institute of Medicine and published by National Academies Press. This book was released on 2011-04-03 with total page 442 pages. Available in PDF, EPUB and Kindle. Book excerpt: Rare diseases collectively affect millions of Americans of all ages, but developing drugs and medical devices to prevent, diagnose, and treat these conditions is challenging. The Institute of Medicine (IOM) recommends implementing an integrated national strategy to promote rare diseases research and product development.
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 Tumor Board Review written by Robert F. Todd and published by Demos Medical Publishing. This book was released on 2011-10-19 with total page 377 pages. Available in PDF, EPUB and Kindle. Book excerpt: Tumor Board Reviews provides comprehensive coverage of all topics in oncology. Each of the 32 chapters focuses on a specific major disease. A brief overview of epidemiology and risk factors is followed by a sequence of specific presentations organized by tumors stage or disease classification. Each discussion features a case presentation that mimics the format of a tumor board presentation and thus illustrates key diagnostic and management decisions. There is also a discussion of the evidence that supports the clinical management decisions taken in the case, based on current expert panel guidelines. Algorithms and decision tree graphics are used extensively to provide visual support of the decision process. The combination of case presentations and evidence-based management discussions make this volume a unique tool for keeping current with clinical guidelines and provides the reader with a clear understanding of applications of new information for use in daily practice.
Download or read book Clinical Trials in Oncology Third Edition written by Stephanie Green and published by CRC Press. This book was released on 2012-05-09 with total page 266 pages. Available in PDF, EPUB and Kindle. Book excerpt: The third edition of the bestselling Clinical Trials in Oncology provides a concise, nontechnical, and thoroughly up-to-date review of methods and issues related to cancer clinical trials. The authors emphasize the importance of proper study design, analysis, and data management and identify the pitfalls inherent in these processes. In addition, the book has been restructured to have separate chapters and expanded discussions on general clinical trials issues, and issues specific to Phases I, II, and III. New sections cover innovations in Phase I designs, randomized Phase II designs, and overcoming the challenges of array data. Although this book focuses on cancer trials, the same issues and concepts are important in any clinical setting. As always, the authors use clear, lucid prose and a multitude of real-world examples to convey the principles of successful trials without the need for a strong statistics or mathematics background. Armed with Clinical Trials in Oncology, Third Edition, clinicians and statisticians can avoid the many hazards that can jeopardize the success of a trial.
Download or read book IASLC Thoracic Oncology E Book written by Harvey Pass and published by Elsevier Health Sciences. This book was released on 2017-04-21 with total page 960 pages. Available in PDF, EPUB and Kindle. Book excerpt: Global experts, in conjunction with the International Association for the Study of Lung Cancer, bring you up to date with today’s best approaches to lung cancer diagnosis, treatment, and follow-up. IASLC Thoracic Oncology, 2nd Edition, keeps you abreast of the entire scope of this fast-changing field, from epidemiology to diagnosis to treatment to advocacy. Written in a straightforward, practical style for the busy clinician, this comprehensive, multidisciplinary title is a must-have for anyone involved in the care of patients with lung cancer and other thoracic malignancies. Offers practical, relevant coverage of basic science, epidemiology, pulmonology, medical and radiation oncology, surgery, pathology, palliative care, nursing, and advocacy. Provides authoritative guidance from the IASLC – the only global organization dedicated to the study of lung cancer. Includes new content on molecular testing, immunotherapy, early detection, staging and the IASLC staging system, surgical resection for stage I and stage II lung cancer, and stem cells in lung cancer. Features a new full-color design throughout, as well as updated diagnostic algorithms.
Download or read book Circulating tumor DNA in cancer A role as a response and monitoring next generation biomarker in cancer therapy written by Saeid Latifi-Navid and published by Frontiers Media SA. This book was released on 2023-06-23 with total page 120 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Improving and Accelerating Therapeutic Development for Nervous System Disorders written by Institute of Medicine and published by National Academies Press. This book was released on 2014-02-06 with total page 107 pages. Available in PDF, EPUB and Kindle. Book excerpt: Improving and Accelerating Therapeutic Development for Nervous System Disorders is the summary of a workshop convened by the IOM Forum on Neuroscience and Nervous System Disorders to examine opportunities to accelerate early phases of drug development for nervous system drug discovery. Workshop participants discussed challenges in neuroscience research for enabling faster entry of potential treatments into first-in-human trials, explored how new and emerging tools and technologies may improve the efficiency of research, and considered mechanisms to facilitate a more effective and efficient development pipeline. There are several challenges to the current drug development pipeline for nervous system disorders. The fundamental etiology and pathophysiology of many nervous system disorders are unknown and the brain is inaccessible to study, making it difficult to develop accurate models. Patient heterogeneity is high, disease pathology can occur years to decades before becoming clinically apparent, and diagnostic and treatment biomarkers are lacking. In addition, the lack of validated targets, limitations related to the predictive validity of animal models - the extent to which the model predicts clinical efficacy - and regulatory barriers can also impede translation and drug development for nervous system disorders. Improving and Accelerating Therapeutic Development for Nervous System Disorders identifies avenues for moving directly from cellular models to human trials, minimizing the need for animal models to test efficacy, and discusses the potential benefits and risks of such an approach. This report is a timely discussion of opportunities to improve early drug development with a focus toward preclinical trials.
Download or read book Adaptive Design Methods in Clinical Trials written by Shein-Chung Chow and published by CRC Press. This book was released on 2011-12-01 with total page 368 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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
Download or read book Novel Designs of Early Phase Trials for Cancer Therapeutics written by Shivaani Kummar and published by Academic Press. This book was released on 2018-05-22 with total page 235 pages. Available in PDF, EPUB and Kindle. Book excerpt: Novel Designs of Early Phase Trials for Cancer Therapeutics provides a comprehensive review by leaders in the field of the process of drug development, the integration of molecular profiling, the changes in early phase trial designs, and endpoints to optimally develop a new generation of cancer therapeutics. The book discusses topics such as statistical perspectives on cohort expansions, the role and application of molecular profiling and how to integrate biomarkers in early phase trials. Additionally, it discusses how to incorporate patient reported outcomes in phase one trials. This book is a valuable resource for medical oncologists, basic and translational biomedical scientists, and trainees in oncology and pharmacology who are interested in learning how to improve their research by using early phase trials. Brings a comprehensive review and recommendations for new clinical trial designs for modern cancer therapeutics Provides the reader with a better understanding on how to design and implement early phase oncology trials Presents a better and updated understanding of the process of developing new treatments for cancer, the exciting scientific advances and how they are informing drug development
Download or read book Statistical Methods in Drug Combination Studies written by Wei Zhao and published by CRC Press. This book was released on 2014-12-19 with total page 236 pages. Available in PDF, EPUB and Kindle. Book excerpt: The growing interest in using combination drugs to treat various complex diseases has spawned the development of many novel statistical methodologies. The theoretical development, coupled with advances in statistical computing, makes it possible to apply these emerging statistical methods in in vitro and in vivo drug combination assessments. Howeve
Download or read book Journal of the National Cancer Institute written by and published by . This book was released on 2013 with total page 548 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book 1970 Census of Population written by and published by . This book was released on 1988 with total page 196 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book NIH Almanac written by National Institutes of Health (U.S.). Division of Public Information and published by . This book was released on 1988 with total page 138 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Principles of Anticancer Drug Development written by Elizabeth Garrett-Mayer and published by Springer Science & Business Media. This book was released on 2010-12-29 with total page 673 pages. Available in PDF, EPUB and Kindle. Book excerpt: A practical guide to the design, conduction, analysis and reporting of clinical trials with anticancer drugs.
