Applied Statistical Considerations For Clinical Researchers

This essential book details intermediate-level statistical methods and frameworks for the clinician and medical researcher with an elementary grasp of health statistics and focuses on selecting the appropriate statistical method for many scenarios. Detailed evaluation of various methodologies familiarizes readers with the available techniques and equips them with the tools to select the best from a range of options. The inclusion of a hypothetical case study between a clinician and statistician charting the conception of the research idea through to results dissemination enables the reader to understand how to apply the concepts covered into their day-to-day clinical practice. Applied Statistical Considerations for Clinical Researchers focuses on how clinicians can approach statistical issues when confronted with a medical research problem by considering the data structure, how this relates to their study's aims and any potential knock-on effects relating to the evidence required to make correct clinical decisions. It covers the application of intermediate-level techniques in health statistics making it an ideal resource for the clinician seeking an up-to-date resource on the topic.

This essential book details intermediate-level statistical methods and frameworks for the clinician and medical researcher with an elementary grasp of health statistics and focuses on selecting the appropriate statistical method for many scenarios. Detailed evaluation of various methodologies familiarizes readers with the available techniques and equips them with the tools to select the best from a range of options. The inclusion of a hypothetical case study between a clinician and statistician charting the conception of the research idea through to results dissemination enables the reader to understand how to apply the concepts covered into their day-to-day clinical practice. Applied Statistical Considerations for Clinical Researchers focuses on how clinicians can approach statistical issues when confronted with a medical research problem by considering the data structure, how this relates to their study's aims and any potential knock-on effects relating to the evidence required to make correct clinical decisions. It covers the application of intermediate-level techniques in health statistics making it an ideal resource for the clinician seeking an up-to-date resource on the topic.

In 1948 the first randomized controlled trial was published by the English Medical Research Council in the British Medical Journal. Until then, observations had been uncontrolled. Initially, trials frequently did not confirm the hypotheses to be tested. This phenomenon was attributed to low sensitivity due to small samples, as well as inappropriate hypotheses based on biased prior trials. Additional flaws were recognized and, subsequently, were better accounted for: carryover effects due to insufficient washout from previous treatments, time effects due to external factors and the natural history of the condition under study, bias due to asymmetry between treatment groups, lack of sensitivity due to a negative correlation between treatment responses, and so on. Such flaws, mainly of a technical nature, have been largely corrected and led to trials after 1970 being of significantly higher quality. The past decade has focused, in addition to technical aspects, on the need for circumspection in the planning and conducting of clinical trials. As a consequence, prior to approval, clinical trial protocols are now routinely scrutinized by different circumstantial organs, including ethics committees, institutional and federal review boards, national and international scientific organizations, and monitoring committees charged with conducting interim analyses. This book not only explains classical statistical analyses of clinical trials, but also addresses relatively novel issues, including equivalence testing, interim analyses, sequential analyses, and meta-analyses, and provides a framework of the best statistical methods currently available for such purposes. This book is not only useful for investigators involved in the field of clinical trials, but also for all physicians who wish to better understand the data of trials as currently published.

In clinical trial practice, controversial statistical issues inevitably occur regardless of the compliance with good statistical practice and good clinical practice. But by identifying the causes of the issues and correcting them, the study objectives of clinical trials can be better achieved. Controversial Statistical Issues in Clinical Trials covers commonly encountered controversial statistical issues in clinical trials and, whenever possible, makes recommendations to resolve these problems. The book focuses on issues occurring at various stages of clinical research and development, including early-phase clinical development (such as bioavailability/bioequivalence), bench-to-bedside translational research, and late-phase clinical development. Numerous examples illustrate the impact of these issues on the evaluation of the safety and efficacy of the test treatment under investigation. The author also offers recommendations regarding possible resolutions of the problems. Written by one of the preeminent experts in the field, this book provides a useful desk reference and state-of-the art examination of problematic issues in clinical trials for scientists in the pharmaceutical industry, medical/statistical reviewers in government regulatory agencies, and researchers and students in academia.

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.

The explanation and implementation of statistical methods for themedical researcher or statistician remains an integral part ofmodern medical research. This book explains the use of experimentaland analytical biostatistics systems. Its accessible style allowsit to be used by the non-mathematician as a fundamental componentof successful research. Since the third edition, there have been many developments instatistical techniques. The fourth edition provides the medicalstatistician with an accessible guide to these techniques and toreflect the extent of their usage in medical research. The new edition takes a much more comprehensive approach to itssubject. There has been a radical reorganization of the text toimprove the continuity and cohesion of the presentation and toextend the scope by covering many new ideas now being introducedinto the analysis of medical research data. The authors have triedto maintain the modest level of mathematical exposition thatcharacterized the earlier editions, essentially confining themathematics to the statement of algebraic formulae rather thanpursuing mathematical proofs. Received the Highly Commended Certificate in the PublicHealth Category of the 2002 BMA BooksCompetition.

The majority of physicians are poorly knowledgeable about statistics and research design, yet are expected to do clinical research and write articles (if in academia) or, at the very least, to read the literature critically and provide evidence-based care to patients. The basic skills involved are touched on very minimally in residency, but not in enough depth for an untrained investigator to successfully design or conduct a study, or analyze research findings in any meaningful way. This volume is intended as a “quick fix”, allowing readers to look up information rapidly about various design types and statistical methods to see what the pros, cons, and indications for each are. Research implementation, including regulatory issues and grant writing, is also covered. The book is unique in physical medicine and rehabilitation, and with the increased emphasis on outcomes measurement and push toward a national agenda for disability research, will appeal both to investigators planning and executing studies and clinicians looking to better understand how the findings impact their practice. A list of topics with an outline of headings for each of the sections is attached.

"This is truly an outstanding book. [It] brings together all of the latest research in clinical trials methodology and how it can be applied to drug development.... Chang et al provide applications to industry-supported trials. This will allow statisticians in the industry community to take these methods seriously." Jay Herson, Johns Hopkins University The pharmaceutical industry's approach to drug discovery and development has rapidly transformed in the last decade from the more traditional Research and Development (R & D) approach to a more innovative approach in which strategies are employed to compress and optimize the clinical development plan and associated timelines. However, these strategies are generally being considered on an individual trial basis and not as part of a fully integrated overall development program. Such optimization at the trial level is somewhat near-sighted and does not ensure cost, time, or development efficiency of the overall program. This book seeks to address this imbalance by establishing a statistical framework for overall/global clinical development optimization and providing tactics and techniques to support such optimization, including clinical trial simulations. Provides a statistical framework for achieve global optimization in each phase of the drug development process. Describes specific techniques to support optimization including adaptive designs, precision medicine, survival-endpoints, dose finding and multiple testing. Gives practical approaches to handling missing data in clinical trials using SAS. Looks at key controversial issues from both a clinical and statistical perspective. Presents a generous number of case studies from multiple therapeutic areas that help motivate and illustrate the statistical methods introduced in the book. Puts great emphasis on software implementation of the statistical methods with multiple examples of software code (both SAS and R). It is important for statisticians to possess a deep knowledge of the drug development process beyond statistical considerations. For these reasons, this book incorporates both statistical and "clinical/medical" perspectives.