NIH HEAL InitiativeSM - Sickle Cell Disease Pain Management Large-Scale Clinical Trials (Upcoming FOAs)

NIH HEAL InitiativeSM - Sickle Cell Disease Pain Management Large-Scale Clinical Trials (Upcoming FOAs) is sponsored by National Institutes of Health (NIH) - National Center for Complementary and Integrative Health (NCCIH) with other NIH Institutes, Centers and Offices. This opportunity supports mission-aligned projects and measurable outcomes.

Expired RFA-AT-22-004: HEAL Initiative: Pragmatic and Implementation Studies for the Management of Sickle Cell Disease Pain (UG3/UH3, Clinical Trials Optional) This notice has expired. Check the NIH Guide for active opportunities and notices. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations National Center for Complementary and Integrative Health ( NCCIH ) National Eye Institute ( NEI ) National Heart, Lung, and Blood Institute ( NHLBI ) National Institute of Arthritis and Musculoskeletal and Skin Diseases ( NIAMS ) National Institute on Drug Abuse ( NIDA ) National Institute of Nursing Research ( NINR ) National Institute on Minority Health and Health Disparities ( NIMHD ) All applications to this funding opportunity announcement should fall within the mission of the Institutes/Centers.

The following NIH Offices may co-fund applications assigned to those Institutes/Centers.

Office of Behavioral and Social Sciences Research ( OBSSR ) Office of Research on Women's Health ( ORWH ) Funding Opportunity Title HEAL Initiative: Pragmatic and Implementation Studies for the Management of Sickle Cell Disease Pain (UG3/UH3, Clinical Trials Optional) UG3 / UH3 Exploratory/Developmental Phased Award Cooperative Agreement July 13, 2022 - This RFA has been reissued as RFA-AT-23-001 November 18, 2021 - Notice of Correction to NHLBI-Specific language in RFA-AT-22-004, "HEAL Initiative: Pragmatic and Implementation Studies for the Management of Sickle Cell Disease Pain (UG3/UH3, Clinical Trials Optional)".

See Notice NOT-HL-22-005 Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity UG3 / UH3 Phase 1 Exploratory/Developmental Cooperative Agreement/Exploratory/Developmental Cooperative Agreement Phase II See Section III. 3. Additional Information on Eligibility .

Assistance Listing Number(s) 93. 213, 93. 867, 93.

838, 93. 839, 93. 837, 93.

840, 93. 233, 93. 846, 93.

279, 93. 307, 93. 313, 93.

361 Funding Opportunity Purpose The purpose of this Funding Opportunity Announcement (FOA) is to solicit cooperative agreement applications to conduct multisite embedded pragmatic or implementation trials to inform the uptake of pharmacologic, nonpharmacologic, and/or multicomponent approaches for acute and/or chronic sickle cell disease (SCD) pain management in health care systems that serve the SCD population.

Trials may include or allow continuation of opioid medication as needed; however opioid medication use alone should not be the only intervention studied. 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/or 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.

This FOA requires that the intervention under study be embedded into health care delivery system, real world settings, and it is expected that most data will be obtained through the electronic records of the health care system. Trials should be conducted across three or more health care systems (HCS) that provide care to SCD patient populations.

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) Program Coordinating Center, which has dedicated pain, implementation science, and pragmatic clinical trial design. Awarded applicants will work with the Health Care Systems Research Collaboratory Coordinating Center (HCS CCC) ( https://rethinkingclinicaltrials.

org/ ) to facilitate further planning and refinement of the proposed study in partnerships with health care delivery systems. Awards made under this FOA will support a milestone-driven planning phase (UG3) for 1 year, with possible transition to a clinical trial implementation phase (UH3) of up to an additional four years.

Only UG3 projects that meet the scientific milestones and feasibility requirements will transition to the UH3 phase. The UG3/UH3 application must be submitted as a single application, following the instructions described in this FOA. Open Date (Earliest Submission Date) Letter of Intent Due Date(s) Renewal / Resubmission / Revision (as allowed) All applications are due by 5:00 PM local time of applicant organization.

All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s). Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

Required Application Instructions It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide ,except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts ). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced.

Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV . When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information Part 2. Full Text of Announcement Section I.

Funding Opportunity Description Section II. Award Information Section III. Eligibility Information Section IV.

Application and Submission Information Section V. Application Review Information Section VI. Award Administration Information Section VII.

Agency Contacts Section VIII. Other Information Part 2. Full Text of Announcement Section I.

Funding Opportunity Description The purpose of this Funding Opportunity Announcement (FOA) is to solicit cooperative agreement applications to conduct multisite embedded pragmatic or implementation trials to inform the uptake of pharmacologic, nonpharmacologic, and/or multicomponent approaches for acute and/or chronic sickle cell disease (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 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/or 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. This FOA requires that the intervention under study be embedded into health care delivery system, real world settings.

Trials should be conducted across three or more health care systems (HCS) that provide care to SCD patient populations. 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) Program Coordinating Center, which has dedicated pain, implementation science, and pragmatic clinical trial design.

Awarded applicants will work with the Health Care Systems Research Collaboratory Coordinating Center (HCS CCC) ( https://rethinkingclinicaltrials. org/ ) to facilitate further planning and refinement of the proposed study in partnerships with health care delivery systems.

Awards made under this FOA will support a milestone-driven planning phase (UG3) for 1 year, with possible transition to a clinical trial conduct phase (UH3) of up to an additional four years. Only UG3 projects that meet the scientific milestones and feasibility requirements will transition to the UH3 phase. The UG3/UH3 application must be submitted as a single application, following the instructions described in this FOA.

This study is part of the NIH’s Helping to End Addiction Long-term (HEAL) initiative to speed scientific solutions to 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 HEAL Initiative is available at: https://heal.

nih. gov/ . Sickle cell disease (SCD) is the most common inherited blood disorder in the United States, affecting up to 100,000 Americans, predominantly individuals of African descent and those who self-identify as Black (i.e., 1 in 365 African American children born with SCD) and individuals of Hispanic ethnicity (1 in 16,300).

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, and depression. 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 ( https://www. nationalacademies.

org/our-work/addressing-sickle-cell-disease-a-strategic-plan-and-blueprint-for-action#sectionPublications ) and the Pain Management Best Practices Inter-Agency Task Force ( https://www. hhs. gov/ash/advisory-committees/pain/reports/index.

html ) 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 solely 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 SCD ( 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 .

In addition to scientific diversity, applicants should strive to incorporate diversity in their team development plan. Research shows that diverse teams working together and capitalizing on innovative ideas and distinct perspectives outperform homogenous teams. Scientists and trainees from diverse backgrounds and life experiences bring different perspectives, creativity, and individual enterprise to address complex scientific problems.

There are many benefits that flow from a diverse NIH-supported scientific workforce, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved or health disparity populations participate in, and benefit from health research, and enhancing public trust.

Please refer to Notice of NIH's Interest in Diversity ( NOT-OD-20-031) for more details.

For the purpose of this FOA, we define "embedded pragmatic clinical trial" and "implementation research", as follows : 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 ( 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 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.

This FOA solicits applications for UG3/UH3 exploratory/developmental phased award cooperative agreements for projects to support multisite embedded pragmatic or implementation trials to inform the uptake of pharmacologic, nonpharmacologic, and/or multicomponent approaches for acute and/or chronic sickle cell disease (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. Applications are required to conduct the embedded pragmatic or implementation trial across three or more HCS (e.g., pain specialty clinics, hospitals, primary care, emergency rooms, or community health clinics).

It is expected that most data will be obtained through the electronic records of the health care system. Clinical trials will be conducted within the infrastructure of the Pragmatic and Implementation Studies for the Management of Pain to Reduce Opioid Prescribing (PRISM) Program ( https://heal. nih.

gov/research/clinical-research/prism ). The design of the proposed project should maximize external validity of the study, by testing generalizability, feasibility and sustainability of findings across distinct health care settings, and diverse staff and patient populations.

The proposed pragmatic trials or implementation research studies must meet all the following criteria: The project must test an intervention, or coordinate several interventions (which can be treatments, preventive actions, or organizational changes) that are robust, apply to management of SCD pain patient populations and are suitable for use in multiple health systems, with the broad goal of determining whether the intervention(s) improves individual or system level outcomes, and adds value to the utilization of the nation’s health care resources.

The results of the question being tested will have a significant impact on pain management within health care systems (HCS). The intervention(s) must be well-characterized and available such that it could be reliably delivered by clinical providers and/or HCS.

If an intervention includes a drug, biologic or device, it must be a legally marketed drug, biologic or medical device in the US, and used as approved/cleared for use by the Food and Drug Administration. The intervention(s) must be reasonably simple and not require a complex structure for implementation or monitoring. System level interventions may be particularly suitable.

As in routine practice, the project must allow for interventions to be implemented with maximal flexibility and by all appropriate practitioners (not just those with high levels of training or competence). The project must leverage opportunities made available through the health care systems and use outcomes that can be captured with passive follow-up by electronic health records, with minimal need for adjudication.

Augmentation of the electronic health record is allowable for patient reported data and outcomes, although this should be streamlined and collected only at necessary time points. The project outcome measure(s) must be clinically meaningful and important to stakeholders including patients, providers, health care systems, and policy makers.

Additional outcome measures such as use of health care services or medications, and other resources may be included. Outcome measures must provide useful information to medical decision makers, whether patients, care providers, health care systems or payers. The project design must incorporate rigorous controls, prospectively identified, preferably by randomization.

The design may incorporate novel randomization approaches, such as by cluster or timing of implementation. If another method is used to generate the comparison group, perhaps by staged assignment or staged implementation of the intervention, it should provide comparable rigor.

Proposed analytic plans for projects that proposed cluster-randomized trials must address adequacy of sample size and study power, and employ analytic strategies relevant for such pragmatic trial designs. Applicants are strongly encouraged to consult Collaboratory Biostatistical Guidance documents ( http://sites. duke.

edu/rethinkingclinicaltrials/biostatistical-guidance-documents/ ) when developing pragmatic trial analytic plans. The study must address, and potentially overcome, important barriers to research in the setting of HCS partnerships.

The project must enroll SCD patients based on broad eligibility criteria to maximize diversity, and minimize intentional or unintentional exclusions based on risk, age, health literacy, demographics, or expected adherence. Embedded Pragmatic trials must include: Clinical outcomes measures to assess meaningful changes that are defined at the patient, provider, or system level.

Implementation trials must include: Sufficient evidence for the proposed intervention to justify implementation or de-implementation or the need for intervention adaptation. A strategy to de-implement care is proposed for low-value interventions where there is evidence of no benefit or there is more harm than benefit for patients. Main outcomes focused on implementation that are most likely at a system or individual provider level.

Patient-level implementation outcomes may be possible, if focused not on health but on the use of the targeted intervention. There is a conceptual model and theoretical justification of the proposed study design and variables tested with a well-defined strategy and reasonable readiness to adopt if primary outcome met. Partnerships with health care delivery organizations will be critical in conducting this work.

It is anticipated that the Trials will generally be performed with high volume electronically supported integrated HCS to establish efficiencies. The HCS partnership must facilitate access to all data sources relevant to the project, which may include inpatient, outpatient, imaging, clinical laboratory, pharmacy and community data.

Applicants, who may be from academic institutions or other organizations, must demonstrate experience in successful conduct of clinical or implementation research in partnerships with HCS. In general, applicants must identify at least three HCS as partners for the proposed Trial.

If an applicant identifies less than three HCS as partners for the proposed Trial, they must provide a strong scientific rationale for limiting this aspect of the project and address generalizability and adequacy of sampling for the Trial. These projects will be funded as phased awards with a one-year planning phase (UG3) and up to four year implementation phase (UH3).

Activities in both phases will depend on the specific study (e.g., type of interventions, experimental design, randomization strategy and proposed outcome measures). During the UG3 or planning phase, activities will generally include, but are not limited to: Identify project staff that will participate in the PRISM/Collaboratory Work Groups (see Section I. 5 Additional Information https://www.

nihcollaboratory. org/cores/Pages/default. aspx ), which will develop guidelines and practices to be implemented across projects.

Work with the PRISM/Collaboratory Coordinating Center (CCC) to implement approved guidelines and practices for electronic data extraction and quality control methods and tools, as well as for electronic data sharing.

In the planning phase, this will include developing and validating all electronic data methods and tools within the HCS needed for the Project (e.g., electronic health records, electronic methods for patient identification and outcomes assessment, patient reported data, biospecimens, images, high-throughput genomic data, family history data, data abstraction and survey instruments) and complete quality control testing at all sites.

Assess adequacy and finalize clinically relevant outcome measures with other PRISM/Collaboratory investigators.

Awarded applicants will work with other PRISM/Collaboratory investigators and NIH to identify common outcome measures (pain severity, pain interference, and pain functioning, as well as others); and will work with the CCC and NIH to develop metrics for resource utilization for planning and implementing PRISM/Collaboratory pragmatic trials.

If an award is made, NIH and CCC staff will work with the Program Directors/Principal Investigators to facilitate coordination among projects. Refine estimates of requirements with guidance from NIH and the CCC, for sample size, numbers of sites, site to site heterogeneity, and implementation timetable based on data derived from the partnering HCS.

In general, all studies should use at least three HCS for implementation, unless a specific rationale for limiting this aspect of the project is provided. Develop detailed plans for site implementation, including site staff, method of identification, randomization (as applicable) and participant recruitment and acquisition and administration/implementation of the intervention if applicable.

Address all ethical issues and issues related to human subject safety oversight for the Trial, including development of informed consent documents or opt-out consent if applicable, and finalizing site of IRB review. Applicants must propose a consolidated or centralized IRB approach for trial oversight, to facilitate both appropriate and timely study implementation.

Address all potential regulatory elements of the proposed trial (if applicable). Develop a detailed budget for conduct and completion of the Trial, including preparation of a final study report. Finalize detailed plans for data coordination and quality control for the UH3 phase.

The CCC will not provide these functions for individual Trials. Data coordinating activities for individual Projects must be separately budgeted as part of the UH3 budget. Project Trial Conduct Phase (UH3): The objective of the up to four year UH3 trial conduct phase is to conduct the Trial in accordance with activities planned in the UG3 phase.

Activities will depend upon the study, but in general the following goals should be achieved: Each project is expected to conduct all aspects of the proposed pragmatic or implementation trial including the identification and recruitment of proposed sample sizes of patients, practice sites, and clinicians, the execution of the intervention and its delivery with the HCS, and the assessment of outcomes.

Each project is expected to provide complete assessment of all issues related to patient, clinician and site identification, and EHR tools used in these steps. Each project is expected to provide definitive information about the execution of the intervention at all sites. Each project is encouraged to assess fidelity to the intervention, when possible.

Each project is to provide detailed and definitive testing of the validity of methods used for monitoring and outcome assessment. Milestones and UG3/UH3 Transition Utilization of milestones is a key characteristic of this FOA. A milestone is defined as a scheduled event in the project timeline, signifying the completion of a major project stage or activity.

This FOA will utilize a two-phase, milestone-driven cooperative agreement (UG3/UH3) mechanism consisting of a start-up phase of up to one year (UG3) and a pragmatic or implementation trial execution phase (UH3). Projects should include well-defined milestones for the planning phase (UG3) and annual milestones for the trial conduct phase (UH3).

It is understood that the proposed milestones for the UH3 phase will be revised as activities in the UG3 phase progress. In the event of an award, the PD/PI and NIH staff will negotiate a final list of milestones for each year of support. At the completion of the UG3 planning phase, the applicant will be required to submit a detailed transition request for the UH3 Project implementation phase.

UH3 transition requests will undergo an administrative review to determine whether the Project will be awarded for the trial conduct phase (UH3). All regulatory approvals should be obtained prior to the end of the UG3 award.

Training of intervention providers, comparison group providers, or other resources should be planned at the start of the UH3 award to allow for the successful launch and execution of the proposed pragmatic or implementation trial in the UH3 phase. Prospective applicants should note that initial funding of the UG3 phase does not guarantee support of the UH3 trial conduct phase .

Applicants should understand that transition to the UH3 phase of the project will occur only if an administrative review process recommends that the UG3 planning milestones have been successfully met, that the UH3 phase can proceed with confidence of success, and availability of funds. Continuation of the award is conditional upon satisfactory progress and subject to availability of funds.

If, at any time, recruitment falls significantly below the projected milestones for recruitment, the NIH will consider ending support and negotiating an orderly phase-out of the award and retains, as an option, periodic external peer review of progress. NIH staff will closely monitor progress at all stages, milestones, accrual, and safety.

The NIH HEAL Initiative will require a high level of coordination and sharing between investigators. It is expected that NIH HEAL Initiative awardees will cooperate and coordinate their activities after awards are made by participating in Program Director/Principal Investigator (PD/PI) meetings, including an annual HEAL Investigators Meeting, as well as other activities.

Research Areas of Interest Applicants must propose a pragmatic or implementation trial to address one or more critical research questions important for improved SCD pain management within health care systems.

The following list provides examples of some of the potential research questions that might be addressed by such pragmatic trials: Support trials that evaluate the effectiveness of integrating pharmacologic nonpharmacologic and/or multicomponent approaches into pain management care, which may reduce use of opioids; Support trials that examine the impact of interventions on pain management as well as impact on comorbidities such as sleep disturbance, anxiety, and stress.

Trials that evaluate interventions to address social and structural barriers such as stigma and racial bias to improve SCD pain management care. Support embedded pragmatic or implementation trials 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.

Studies focused on improving SCD pain management in emergency rooms, primary care settings, or hospitals. Studies to test the effect of system level innovations to improve implementation of established SCD pain management guidelines.

Comparative effectiveness studies utilizing different combinations of pain management treatments for acute or chronic SCD pain management within health care systems Studies of implementation strategies to support the adoption and integration of effective SCD pain management clinical procedures or guidelines into existing care systems.

Studies to identify effective implementation strategies for integrating multiple evidence-based SCD pain management practices within community or clinical settings to meet the needs of SCD patients and diverse systems of care; and Studies testing the effectiveness and impact on utilization of health care services of implementation strategies to reduce health disparities and improve quality of SCD pain management among rural, minority, low literacy and numeracy, and other underserved population IC-Specific Areas of Interest National Center for Complementary and Integrative Health (NCCIH) The NCCIH is interested in embedded pragmatic or implementation trials that evaluate the effectiveness of complementary and integrative health interventions or how to implement these interventions into health care delivery.

Complementary approaches include those with physical and/or psychological therapeutic inputs, often called mind and body approaches (e.g., acupuncture, yoga, tai chi, qi gong, meditation, hypnosis, music therapy, art therapy, spinal or chiropractic manipulation, and massage) as well as approaches with dietary or nutritional therapeutic inputs (e.g., special diets).

Integrative approaches include therapies that combine complementary approaches with conventional medical interventions such as pharmacologic, surgery, or device-based treatments. In the context of this FOA, NCCIH is particularly interested in encouraging applications that will study the integration of complementary health approaches for SCD pain management into health care delivery.

The complementary interventions should have demonstrated efficacy or effectiveness in fully powered randomized controlled trials.

In addition, NCCIH encourages applications that will study methods to improve adherence to evidence-based pain management guidelines that include complementary and integrative health approaches to reduce the reliance on solely opioid-based treatments and improve functional outcomes (e.g., anxiety, depression, sleep disturbances) to promote a whole health approach to SCD pain management.

Applications that include interventions to mitigate stigma and other structural and social factors (e.g., racism) that may hinder quality comprehensive pain care for patients with SCD are also of interest. Applicants are encouraged to discuss applications with the NCCIH contact listed in Section VII. Agency Contacts.

National Heart, Lung, and Blood Institute (NHLBI) The National Heart, Lung, and Blood Institute (NHLBI) provides global leadership in research, training, and education programs to promote the prevention and treatment of heart, lung, and blood diseases and sleep disorders (HLBS). NHLBI seeks to optimize clinical and implementation research to improve health and reduce disease.

In the context of this FOA, NHLBI is interested in studies of effective strategies to train primary care providers, nurse practitioners and patient care navigators in sickle cell disease pain management, and to incorporate technology (e.g., telemedicine) to extend care by specialists to providers in the community; investigations that use implementation strategies to facilitate care transitions, such as from inpatient to outpatient, or pediatric to adult, to maintain optimal evidence-based SCD pain management care; research on reducing or stopping (de-implementing) the use of HLBS clinical and community practices that are ineffective, unproven, low-value, or harmful; research that focuses on clinical decision support systems to facilitate shared decision-making approaches in clinical and community settings; research on how best to integrate evidence-based interventions across diverse populations and clinical settings that take into account social determinants of health; and studies testing the effectiveness and cost-effectiveness of dissemination or implementation strategies to reduce health disparities and improve health care and quality of life among rural, minority, low literacy and numeracy, and other disproportionately affected populations.

National Eye Institute (NEI) Sickle cell disease can manifest in multiple ways including ophthalmic manifestations such as potential macular thinning, or peripheral retinal ischemia. The NEI is interested in applications that aim at reducing the burden of eye disease associated with sickle cell disease and/or improving patients' visual functioning.

National Institute on Drug Abuse (NIDA) NIDA is interested in research to evaluate pain management interventions that may reduce the severity of opioid use disorders (OUDs) and overdose in patients with