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 effectiveness clinical trials of multicomponent nonopioid pharmacologic and nonpharmacologic approaches for acute and/or chronic sickle cell disease (SCD) pain management. Trials supported under this initiative would also address the impact of these approaches on related psychological and functional outcomes to support improved overall well-being and quality of life. In addition, studies that address stigma, structural health care system, and social factors that may hinder quality comprehensive pain care for patients with SCD are also of interest. Investigators are encouraged to include the collection of well-justified biological markers or psychological processes that have demonstrated that they mediate pain outcomes. Trials should collect sufficient measures to phenotype participants including type of pain, variability of pain, co-occurring conditions, and social determinants of health. The studies must address questions within the mission and research interests of the NIH HEAL Initiative and evaluate preventive or treatment strategies or interventions including medications, biologics, procedures, medical and assistive devices and technologies, behavioral interventions, rehabilitation strategies, complementary interventions, integrated approaches, and delivery system strategies in well controlled trials in patients with SCD to manage acute and/or chronic pain. The overall goal is to inform clinicians about the effectiveness of coordinated, multidisciplinary management strategies that reduce acute and/or chronic SCD pain and that continue to provide access to opioid pain management when needed. Clinical trials will be conducted within the infrastructure of the HEAL Pain Effectiveness Research Network which has dedicated pain and 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 SCD, pain, health disparities, psychosocial research, and clinicians. 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, chronic persistent pain, and neuropathic pain. 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 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.

This initiative will encourage UG3/UH3 phased cooperative research applications to support multisite clinical trials to test the effectiveness of multicomponent nonopioid pharmacologic and nonpharmacologic approaches for acute and/or chronic SCD pain management. Effectiveness 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 also should address the impact of these approaches on related psychological and functional outcomes to support improved overall well-being and quality of life. Trials may also address stigma, structural health care system, and social factors that may hinder quality comprehensive 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 HEAL Pain Effectiveness Research Network which has dedicated pain and clinical trial design expertise. Multi-site trials will require participation of two or more clinical sites for completion of the study (e.g., in order to increase sample size, accelerate recruitment, or increase sample diversity and representation).

See companion Notice (NOT-AT-21-018) for details on a planned HEAL Initiative to support embedded pragmatic trials or implementation studies to evaluate the impact of health care system changes to improve adherence to evidence-based non-opioid pharmacologic and nonpharmacologic approaches for acute and chronic 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 Health (NCCIH)

301-827-6358

[email protected]