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.

Complex mathematical and computational models are used in all areas of society and technology and yet model based science is increasingly contested or refuted, especially when models are applied to controversial themes in domains such as health, the environment or the economy. More stringent standards of proofs are demanded from model-based numbers, especially when these numbers represent potential financial losses, threats to human health or the state of the environment. Quantitative sensitivity analysis is generally agreed to be one such standard. Mathematical models are good at mapping assumptions into inferences. A modeller makes assumptions about laws pertaining to the system, about its status and a plethora of other, often arcane, system variables and internal model settings. To what extent can we rely on the model-based inference when most of these assumptions are fraught with uncertainties? Global Sensitivity Analysis offers an accessible treatment of such problems via quantitative sensitivity analysis, beginning with the first principles and guiding the reader through the full range of recommended practices with a rich set of solved exercises. The text explains the motivation for sensitivity analysis, reviews the required statistical concepts, and provides a guide to potential applications. The book: Provides a self-contained treatment of the subject, allowing readers to learn and practice global sensitivity analysis without further materials. Presents ways to frame the analysis, interpret its results, and avoid potential pitfalls. Features numerous exercises and solved problems to help illustrate the applications. Is authored by leading sensitivity analysis practitioners, combining a range of disciplinary backgrounds. Postgraduate students and practitioners in a wide range of subjects, including statistics, mathematics, engineering, physics, chemistry, environmental sciences, biology, toxicology, actuarial sciences, and econometrics will find much of use here. This book will prove equally valuable to engineers working on risk analysis and to financial analysts concerned with pricing and hedging.

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)

This book trains the next generation of scientists representing different disciplines to leverage the data generated during routine patient care. It formulates a more complete lexicon of evidence-based recommendations and support shared, ethical decision making by doctors with their patients. Diagnostic and therapeutic technologies continue to evolve rapidly, and both individual practitioners and clinical teams face increasingly complex ethical decisions. Unfortunately, the current state of medical knowledge does not provide the guidance to make the majority of clinical decisions on the basis of evidence. The present research infrastructure is inefficient and frequently produces unreliable results that cannot be replicated. Even randomized controlled trials (RCTs), the traditional gold standards of the research reliability hierarchy, are not without limitations. They can be costly, labor intensive, and slow, and can return results that are seldom generalizable to every patient population. Furthermore, many pertinent but unresolved clinical and medical systems issues do not seem to have attracted the interest of the research enterprise, which has come to focus instead on cellular and molecular investigations and single-agent (e.g., a drug or device) effects. For clinicians, the end result is a bit of a “data desert” when it comes to making decisions. The new research infrastructure proposed in this book will help the medical profession to make ethically sound and well informed decisions for their patients.