Welcome to Rethinking Clinical Trials: A Living Textbook of Pragmatic Clinical Trials
Kevin Weinfurt, PhD, Editor-in-Chief of the Living Textbook, provides an introduction to the site
Our goal in creating Rethinking Clinical Trials is to provide a living resource to guide the many different people with an interest in pragmatic clinical trials (PCTs) (Tunis SR et al. 2003) and research that engages healthcare delivery organizations as partners. PCTs are intended to generate actionable clinical evidence at a fraction of the typical cost and time needed to conduct a traditional trial. In contrast to traditional trials, PCTs measure outcomes that address the basic benefits, burdens, and risks of an intervention, rather than outcomes that might explain the mechanism of the intervention’s effects or lack of effect. The activities in PCTs are ideally performed in real-world, clinical settings with highly generalizable populations. In this way, the process of clinical investigation becomes a “natural outgrowth of patient care,” (Institute of Medicine 2007) fueling a learning healthcare system that continually supplies new knowledge to improve clinical practice and outcomes.
PCTs present an opportunity to efficiently address critical knowledge gaps and generate high-quality evidence to inform medical decision-making. However, the design, conduct, and dissemination of these trials pose different challenges than are typically encountered with traditional clinical trials. For example, the regulatory and ethical scaffolding for research around traditional randomized controlled trials might not fit PCTs; new randomization strategies for PCTs have biostatistical ramifications; and the inclusion of a broader segment of participants necessitates a greater degree of stakeholder and health system engagement. This textbook focuses on the distinctive elements of PCTs at each phase in the research process, from the development of a clinical question to the dissemination of results. Many of the issues addressed are applicable to other types of clinical trials, especially those that rely on real-world evidence, but we focus on PCTs because we are drawing on experiences from the National Institutes of Health (NIH) Health Care Systems Research Collaboratory.
The information, tools, and lessons provided in this online textbook have accumulated from activities of the NIH Collaboratory, which supports the rapid execution of innovative and collaborative projects, including PCTs designed to address issues of major public health importance. In the NIH Collaboratory, NIH and external (or “extramural”) investigators work together under joint governance through a cooperative agreement. The program includes a Coordinating Center, several PCT Demonstration Projects testing innovative designs in pragmatic research, and a set of Cores or Working Groups that generate guidance and assist the Demonstration Projects with the unique challenges in initiating and implementing PCTs (e.g., biostatistics, stakeholder engagement, ethical/regulatory issues).
The Living Textbook reflects a collection of expert consensus regarding special considerations, standard approaches, and best practices in the design, conduct, and reporting of PCTs. We hope that the Living Textbook will be useful to a broad spectrum of users, including clinical trialists, healthcare professionals and administrators, personnel working in academic and industry-funded clinical trials, and the public. The Living Textbook is organized in chapters that follow the linear progression through the process of conducting a PCT. For those interested in further detail, additional resources are listed where appropriate. Readers can also search the NIH Collaboratory Knowledge Repository archive for additional Grand Rounds presentations, peer-reviewed articles, white papers, guidance documents, and tools related to PCTs. Given the rapid pace of change in the field of PCTs, we expect that this electronic textbook will continue to be added to and updated.
This work was supported by a cooperative agreement (U54 AT007748) from the NIH Common Fund for the NIH Health Care Systems Research Collaboratory. The views presented here are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health, the U.S. Department of Health and Human Services, or any of its agencies.
Institute of Medicine. 2007. The Learning Healthcare System: Workshop Summary. Olsen L, Aisner D, McGinnis JM, editors. Washington, DC: National Academies Press. http://www.iom.edu/Reports/2007/The-Learning-Healthcare-System-Workshop-Summary.aspx
Tunis SR, Stryer DB, Clancy CM. 2003. Practical clinical trials: Increasing the value of clinical research for decision making in clinical and health policy. JAMA 290:1624–1632. doi:10.1001/jama.290.12.1624. PMID: 14506122.