Key Dates

The National Institutes of Health (NIH) HEAL (Helping to End Addiction Long-term^SM) Initiative intends to promote a new initiative by publishing a Funding Opportunity Announcement (FOA) soliciting applications to support multisite pragmatic or implementation trials to inform the uptake of non-opioid pharmacologic and nonpharmacologic approaches for acute and chronic sickle cell disease (SCD) pain management in health care systems that serve the SCD population. Trials supported under this initiative could also address social and structural barriers such as stigma and racial bias to SCD pain management care. The overall goal of this initiative is to support the "real world" assessment of pain management interventions and health care strategies to enhance adherence to pain management guidelines in health care systems that may lead to improved SCD pain management, allowing access to opioid pain management when needed. Clinical trials will be conducted within the infrastructure of the HEAL Pragmatic and Implementation Studies for the Management of Pain to Reduce Opioid Prescribing (PRISM) Network which has dedicated pain, implementation science, and pragmatic clinical trial design expertise.

The purpose of this Notice is to allow potential applicants sufficient time to develop meaningful collaborations among investigators with expertise in sickle cell disease, health disparities, pain management, pragmatic clinical trials, implementation trials, and methods to improve adherence to evidence-based medical guidelines. It will also allow potential applicants sufficient time to develop responsive projects.

The FOA is expected to be published in Fall 2021, with an expected application due date in Winter 2021.

This FOA will utilize the UG3/UH3 activity code, a bi-phasic, milestone-driven cooperative agreement. The UG3 phase will provide funding for a one-year planning phase. The second, UH3 phase will provide up to four years of funding for clinical trial implementation. Transition from the UG3 to the UH3 will depend on successful completion of milestones established for the UG3. Applications must address planned activities for both the UG3 and UH3 phases.

Details of the planned FOA are provided below.

This effort is part of the NIH HEAL (Helping to End Addiction Long-term^SM) Initiative to speed the development and implementation of scientific solutions to the national opioid public health crisis. The NIH HEAL Initiative^SMwill bolster research across NIH to (1) improve treatment and prevention of opioid misuse and opioid use disorder and (2) enhance pain management. More information and periodic updates about the Initiative are available at: https://heal.nih.gov/

The most common complication of SCD is pain, including severe acute pain episodes primarily from vaso-occlusive crises and chronic persistent pain, including nociceptive and neuropathic. SCD pain symptoms span from childhood through adulthood and contribute to high rates of hospitalizations, emergency room visits, poor functional and psychosocial outcomes, and an increased rate of mortality. Management of acute and chronic pain among individuals with SCD is complex and often includes treatment such as opioid-based therapies which do not always address other co-occurring symptoms that may exacerbate pain, such as sleep disturbances, stress, anxiety, depression, and increased risk of opioid addiction. Even after curative SCD therapy, severe chronic pain continues for a significant proportion of individuals.

Further, the SCD population primarily comprises racial and ethnic minorities who experience disparities in receiving quality comprehensive care for SCD, including pain management. These disparities have been linked to the stigma associated with this disease as well as social factors such as racism and socioeconomic status. In turn this stigma associated with SCD impacts health outcomes, health seeking behavior, and patient-provider interactions. Indeed, recent reports from the National Academy of Sciences and the Pain Management Best Practices Inter-Agency Task Force highlight the need for a paradigm shift to provide comprehensive care delivery models for managing pain and improving the overall well-being and quality of life of individuals with SCD associated pain. To address these combined challenges, a biopsychosocial approach to pain management that includes a multidisciplinary approach that addresses biological, psychological, and social influences on pain provides an opportunity to treat the whole person, improve overall health status, and possibly mitigate some of the factors leading to the stigma associated with SCD.

While opioid therapy remains vital for the current management of acute SCD pain, non-opioid pharmacologic and nonpharmacologic approaches for pain management have been deemed feasible and of interest to individuals with SCD. Research is needed to enhance the evidence base regarding the real-world effectiveness of multicomponent non-opioid pharmacologic and nonpharmacologic approaches for acute and chronic SCD pain management approaches to reduce different SCD pain types, improve related psychological and functional outcomes, and reduce reliance on opioid-based treatments. Trials are needed to build an evidence base for how to implement effective pain management approaches into health care delivery for patients with sickle cell disease (https://www.nationalacademies.org/our-work/addressing-sickle-cell-disease-a-strategic-plan-and-blueprint-for-action#sectionPublications), as well as how to implement and increase adherence to pain management guidelines for patients with SCD (https://ashpublications.org/bloodadvances/article/4/12/2656/460974/American-Society-of-Hematology-2020-guidelines-for). To design and deliver effective approaches aimed at reducing stigma, reducing pain, and improving health outcomes, additional research is needed to determine effective implementation strategies to reduce stigma and address pain management health inequities for patients with sickle cell disease.

This initiative will encourage UG3/UH3 phased cooperative research applications to support multisite pragmatic or implementation trials to inform the uptake of non-opioid pharmacologic and nonpharmacologic approaches for acute and chronic SCD pain management in health care systems that serve the SCD population. Trials may include or allow continuation of opioid medication use if appropriate, however opioid medication use alone should not be the only intervention studied. Trials supported in this initiative may also focus on addressing social and structural barriers such as stigma and racial bias in SCD pain management care. Applicants are encouraged to include participants across the lifespan including children, emerging adults, and adult populations, as appropriate. Clinical trials will be conducted within the infrastructure of the Pragmatic and Implementation Studies for the Management of Pain to Reduce Opioid Prescribing (PRISM) Network which has dedicated pain, implementation science, and clinical trial design expertise. Applications will be required to conduct the pragmatic or implementation trial across multiple health care systems (e.g., pain specialty clinics, hospitals, primary care, emergency rooms, or community health clinics).

For the purpose of this Notice of Intent to Publish, we define "embedded pragmatic clinical trial" and "implementation research", as follows:

Embedded pragmatic clinical trialsare 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 (https://www.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 policy-makers), 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) either an intent to (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 (http://rethinkingclinicaltrials.org/chapters/pragmatic-clinical-trial/what-is-a-pragmatic-clinical-trial-2/)."

Implementation researchseeks 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.

See companion Notice (NOT-AT-21-017) for details on a planned HEAL Initiative to support multisite clinical trials to test the effectiveness of multicomponent nonopioid pharmacologic and nonpharmacologic approaches for acute and/or chronic sickle cell disease (SCD) pain management.

Applications are not being solicited at this time.

Please direct all inquiries to:

Della White, Ph.D.

National Center for Complementary and Integrative Medicine (NCCIH)

301-827-6358

[email protected]