There is growing recognition that the United States' clinical trials enterprise (CTE) faces great challenges. There is a gap between what is desired - where medical care is provided solely based on high quality evidence - and the reality - where there is limited capacity to generate timely and practical evidence for drug development and to support medical treatment decisions. With the need for transforming the CTE in the U.S. becoming more pressing, the IOM Forum on Drug Discovery, Development, and Translation held a two-day workshop in November 2011, bringing together leaders in research and health care. The workshop focused on how to transform the CTE and discussed a vision to make the enterprise more efficient, effective, and fully integrated into the health care system. Key issue areas addressed at the workshop included: the development of a robust clinical trials workforce, the alignment of cultural and financial incentives for clinical trials, and the creation of a sustainable infrastructure to support a transformed CTE. This document summarizes the workshop.

An ideal health care system relies on efficiently generating timely, accurate evidence to deliver on its promise of diminishing the divide between clinical practice and research. There are growing indications, however, that the current health care system and the clinical research that guides medical decisions in the United States falls far short of this vision. The process of generating medical evidence through clinical trials in the United States is expensive and lengthy, includes a number of regulatory hurdles, and is based on a limited infrastructure. The link between clinical research and medical progress is also frequently misunderstood or unsupported by both patients and providers. The focus of clinical research changes as diseases emerge and new treatments create cures for old conditions. As diseases evolve, the ultimate goal remains to speed new and improved medical treatments to patients throughout the world. To keep pace with rapidly changing health care demands, clinical research resources need to be organized and on hand to address the numerous health care questions that continually emerge. Improving the overall capacity of the clinical research enterprise will depend on ensuring that there is an adequate infrastructure in place to support the investigators who conduct research, the patients with real diseases who volunteer to participate in experimental research, and the institutions that organize and carry out the trials. To address these issues and better understand the current state of clinical research in the United States, the Institute of Medicine's (IOM) Forum on Drug Discovery, Development, and Translation held a 2-day workshop entitled Transforming Clinical Research in the United States. The workshop, summarized in this volume, laid the foundation for a broader initiative of the Forum addressing different aspects of clinical research. Future Forum plans include further examining regulatory, administrative, and structural barriers to the effective conduct of clinical research; developing a vision for a stable, continuously funded clinical research infrastructure in the United States; and considering strategies and collaborative activities to facilitate more robust public engagement in the clinical research enterprise.

Data sharing can accelerate new discoveries by avoiding duplicative trials, stimulating new ideas for research, and enabling the maximal scientific knowledge and benefits to be gained from the efforts of clinical trial participants and investigators. At the same time, sharing clinical trial data presents risks, burdens, and challenges. These include the need to protect the privacy and honor the consent of clinical trial participants; safeguard the legitimate economic interests of sponsors; and guard against invalid secondary analyses, which could undermine trust in clinical trials or otherwise harm public health. Sharing Clinical Trial Data presents activities and strategies for the responsible sharing of clinical trial data. With the goal of increasing scientific knowledge to lead to better therapies for patients, this book identifies guiding principles and makes recommendations to maximize the benefits and minimize risks. This report offers guidance on the types of clinical trial data available at different points in the process, the points in the process at which each type of data should be shared, methods for sharing data, what groups should have access to data, and future knowledge and infrastructure needs. Responsible sharing of clinical trial data will allow other investigators to replicate published findings and carry out additional analyses, strengthen the evidence base for regulatory and clinical decisions, and increase the scientific knowledge gained from investments by the funders of clinical trials. The recommendations of Sharing Clinical Trial Data will be useful both now and well into the future as improved sharing of data leads to a stronger evidence base for treatment. This book will be of interest to stakeholders across the spectrum of research-from funders, to researchers, to journals, to physicians, and ultimately, to patients.

This unique book is designed to help a medical team become a clinical research team. It includes practical information and tips for the initial stages of clinical research: building a team, negotiating a contract, developing a budget, and writing and improving a patient consent. Chapters describing the nuts and bolts of how to actually perform the study follow, including patient recruiting and retention, screening, follow-ups and handling monitor visits. Finally, there is discussion of the yearly reviews and disclosures and not just surviving, but acing, the all-important Food and Drug Administration audit. Clinical research moves medicine forward and is a necessary part of bringing any new therapy, device, or procedure into routine medical care. However, it can be costly and convoluted, and the methodologies of clinical research are not widely standardized. Decreasing some of the chaos present in American clinical research is the primary goal of this book. The second goal is to improve the understanding and education of those who enter clinical research, whether in the frontline work of the clinical research site, in the middleman companies who have a high turnover rate, at a research hospital or institution, or at medical corporations that depend on good clinical research to bring their products to market. The third reason is to standardize American clinical research and to remove some of the vagaries and inconsistencies in the field. Practical and user-friendly, Developing a Successful Clinical Research Program fills a need for a clear guide to developing and improving a first-class research program in any clinical setting.

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.

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.

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.