Frequently Asked Questions: NIH Health Care Systems Research Collaboratory—Pragmatic and Implementation Trials of Embedded Interventions (UG3/UH3, Clinical Trials Optional)

The U mechanism, or cooperative agreement, is a support mechanism intermediate between a grant and a contract in how it is handled. It is used when there will be substantial Federal scientific or programmatic involvement in the initiative once the award is made. Substantial involvement means that, after award, National Institutes of Health (NIH) scientific or program staff will assist, guide, coordinate, or participate in project activities. All the NIH Health Care Systems Research Collaboratory projects are cooperative agreements.

The NIH Health Care Systems Research Collaboratory is an NIH Common Fund program. It has pioneered approaches for conducting large-scale, cost-effective randomized pragmatic trials in the health care settings where patients normally receive their care. Its trials are performed in real-world settings, and they leverage crucial partnerships to address public health questions that are important to patients, their care providers, and payers, as well as researchers. The National Center for Complementary and Integrative Health (NCCIH) and the National Institute on Aging (NIA) have been leading the NIH Collaboratory program.

Embedded pragmatic clinical trials are conducted within the health care delivery setting and are “primarily designed to determine the effects of an intervention under the usual conditions in which it will be applied,” which is in contrast with explanatory trials that “are primarily designed to determine the effects of an intervention under ideal circumstances” (bmj.com/content/350/bmj.h2147). There are “three key attributes of pragmatic clinical trials (PCTs): (1) an intent to inform decision makers (patients, clinicians, administrators, and policymakers), as opposed to elucidating a biological or social mechanism; (2) an intent to enroll a population relevant to the decision in practice and representative of the patients or populations and clinical settings for whom the decision is relevant; and (3) an intent to either (a) streamline procedures and data collection so that the trial can focus on adequate power for informing the clinical and policy decisions targeted by the trial or (b) measure a broad range of outcomes” (rethinkingclinicaltrials.org/chapters/pragmatic-clinical-trial/what-is-a-pragmatic-clinical-trial-2).

Implementation research seeks to understand the behavior of practitioners and support staff, organizations, consumers and family members, and policymakers in context as key influences on the adoption, implementation, and sustainability of evidence-based health interventions and guidelines (e.g., Community Guide to Preventive Services, U.S. Preventive Services Task Force, and clinical and professional societies’ recommendations and guidelines). Implementation research studies should not assume that effective interventions can be integrated into any service setting and for consumer groups and populations without attention to local context, nor that a unidirectional flow of information (e.g., publishing a recommendation, trial, or guideline) is sufficient to achieve practice change.