Frequently Asked Questions: HEAL Initiative: Pragmatic and Implementation Studies for the Management of Sickle Cell Disease Pain (UG3/UH3, Clinical Trials Optional)

This frequently asked questions document includes questions and answers compiled to help researchers interested in a new National Institutes of Health (NIH) funding opportunity announcement (FOA) that solicits phased cooperative research applications to conduct efficient, large-scale pragmatic or implementation trials, embedded within health care systems, to enhance adherence to pain management guidelines in health care systems and improve sickle cell disease (SCD) pain management, allowing access to opioid pain management when needed.

HEAL Initiative: Pragmatic and Implementation Studies for the Management of Sickle Cell Disease Pain (UG3/UH3, Clinical Trials Optional) RFA-AT-22-004.

The receipt date for applications is December 15, 2021.

General Terms and Definitions

1. What is the U mechanism?

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, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. Awards made to this funding opportunity will be cooperative agreements.

2. What is the NIH HEAL Initiative, and how does this FOA support the objectives of the HEAL Initiative?

The NIH Helping to End Addiction Long-term® Initiative, or NIH HEAL Initiative®, is an effort to speed scientific solutions to stem the national opioid public health crisis. The NIH HEAL Initiative bolsters research across NIH to (1) improve treatment for opioid misuse and addiction and (2) enhance pain management. More information about the NIH HEAL Initiative is available at heal.nih.gov. The overall goal of this program is to support real-world assessment of pain management interventions and/or health care strategies that enhance adherence to pain management guidelines in health care systems, which may lead to improved SCD pain management, allowing access to opioid pain management when needed.

3. What are embedded pragmatic trials?

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).

4. What is implementation research?

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.