Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization.

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.

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 2. Full Text of Announcement

Section I. Funding Opportunity Description

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 use if appropriate, however opioid medication use alone should not be the only intervention studied. Trials may propose methods to implement, improve adherence, or evaluate the effectiveness of guidelines for pain management in patients with SCD in various health care settings. 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 expertise in pain, implementation science, and pragmatic clinical trial design. Awarded applicants will work with the PRISM/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 or 2 years, with possible transition to a clinical trial conduct phase (UH3) of up to an additional four years. Only UG3 projects with a planned vanguard pilot may request 2 years for the planning phase with up to 3 years for the UH3 implementation phase; all other projects may request 1 year for the UG3 phase with up to 4 years for the UH3 phase. Total duration of the award will be a maximum of 5 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.

Background

This FOA is issued under 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 is 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/sites/default/files/overview-pmtf-final-report-fact-sheet_508.pdf) 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, improving health outcomes, and address health inequities for patients with sickle cell disease, additional research is needed to determine effective implementation strategies.

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 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.

Research Objectives

This FOA solicits UG3/UH3 exploratory/developmental phased award cooperative agreement applications that propose 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 may propose methods to implement, improve adherence, or evaluate the effectiveness of guidelines for pain management in patients with SCD in various health care settings. 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.

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 SCD pain management within health care systems (HCS) at the individual or systems level.
• 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 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 also 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 propose 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 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 or two year planning phase (UG3) and up to a four-year implementation phase (UH3). UG3 projects with a planned vanguard pilot may request 2 years for the planning phase, all other projects may request 1 year. 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 budgeted as part of the UH3 budget.
• Although not required, investigators may propose a vanguard pilot study if needed during the UG3 planning phase with specific milestones for defining success. A vanguard pilot study can provide an opportunity to make minor adaptations to enhance feasibility of the intervention or when investigators are citing published literature, but do not have direct previous experience with the intervention in the SCD population. If a vanguard study is proposed, it is recommended that this study involve at least two of the study sites. A two-year planning phase is recommended for applications that propose a vanguard pilot study.

Project Trial Conduct Phase (UH3): The objective of the up to four-year UH3 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 one or two years (UG3) and a pragmatic or implementation trial execution phase (UH3). UG3 projects with a planned vanguard pilot may request 2 years for the planning phase, all other projects may request 1 year. 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.

PI Meeting Attendance

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.

In addition, travel to attend two, one-and-a-half-day PRISM/Collaboratory program meetings in the first year, and an annual meeting in subsequent years in the greater Washington D.C. area is expected.

Common Data Elements (CDEs)

The HEAL Clinical Pain Common Data Element (CDE) Initiative provides an unprecedented opportunity for the pain research community to access quality and meaningful data across pain conditions, populations, and multiple interventions. The HEAL CDE initiative aims to facilitate cross-study comparisons, improve interpretability of findings for patient-reported outcomes, and improves the ability to compare results across trials to quantify the impact of interventions. For studies involving human subjects, projects will be required to use the HEAL Clinical Pain Core CDEs which include measures within 9 pain domains and are specific to either adult or pediatric populations and acute or chronic pain conditions. The domains include pain intensity, pain interference, physical functioning/quality of life, sleep, pain catastrophizing, depression, anxiety, treatment satisfaction, and a substance use screener (HEAL CDE Program). Studies that use additional pain screening tools must select from a comprehensive set coded through HEAL or submit their tools for coding to comply with HEAL pain data harmonization. Any outcome measures specific to clinical pain should be validated measures appropriate for the pain condition.

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, acute 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 (e.g., academic, non-profit, or community-based health care systems), ; 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. NIH defines health disparity populations as racial and ethnic minority populations, less privileged socioeconomic status (SES) populations, underserved rural populations, sexual and gender minorities (SGM), and any subpopulations that can be characterized by two or more of these descriptions. See, https://www.nimhd.nih.gov/about/strategic-plan/nih-strategic-plan-definitions-and-parameters.

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 minority health and health disparity 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. As noted above, NIH defines health disparity populations as racial and ethnic minority populations, less privileged socioeconomic status (SES) populations, underserved rural populations, sexual and gender minorities (SGM), and any subpopulations that can be characterized by two or more of these descriptions.

National Institute of Nursing Research (NINR)

The National Institute of Nursing Research (NINR) supports research to solve pressing health challenges and inform practice and policy - optimizing health and advancing health equity into the future. NINR discovers solutions to health challenges through the lenses of health equity, social determinants of health, population and community health, prevention and health promotion, and systems and models of care. Drawing on the strengths of nursing’s holistic, contextualized perspective, core values, and broad reach, NINR funds multilevel and cross-sectoral research that examines the factors that impact health across the many settings in which nurses work, including homes, schools, workplaces, clinics, justice settings, and the community. Observational, intervention, and implementation research are of interest.

In the context of this FOA, NINR’s interests include but are not limited to the following topics:

Studies of SCD pain management that address SCD health-related social risk factors and social needs within the context of clinical practice and health care delivery

Research that addresses stigma, access to quality care, bias, and structural barriers impacting health outcomes, health seeking behavior, and patient-provider interactions

Projects aimed at under-served, uninsured, and under-insured SCD populations

Trials that include efforts to identify and eliminate negative effects of implicit bias in healthcare providers

Multidisciplinary, multi-level interventions or multi-component delivery models that engage the SCD community

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 Minority Health and Health Disparities (NIMHD)

The mission of NIMHD is to lead, conduct and support scientific research to improve minority health and reduce health disparities. NIH defines health disparity populations as racial and ethnic minority populations (including Blacks/African Americans, Hispanics/Latinos, American Indians/Alaska Natives, Asian Americans, Native Hawaiians and other Pacific Islanders), less privileged socioeconomic status (SES) populations, underserved rural populations, sexual and gender minorities (SGM), and any subpopulations that can be characterized by two or more of these descriptions. In the context of this FOA, NIMHD is particularly interested in encouraging applications that include, but are not limited to: address the intersection of acute and chronic pain management in SCD and ways to maintain continuity of care in patients with acute and chronic pain, and multilevel strategies to improve services for SCD, strategies to address social determinants of health for improving minority health and reducing health disparities; research on the outcomes of implementation, management and treatment of acute and chronic pain in SCD; conduct subpopulation analysis to determine which interventions work best for specific NIH-designated populations that experience health disparitieswith the intent to focus on improving quality of life. We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

Office of Research on Women’s Health (ORWH)

The Office of Research on Women's Health (ORWH) is part of the Office of the Director of NIH and works in partnership with the 27 NIH Institutes and Centers to ensure that women's health research is part of the scientific framework at the NIH and throughout the scientific community.

Sickle cell disease (SCD) is the most common inherited blood disorder in the United States. The most common complication of SCD is pain, including severe acute pain, chronic persistent pain, and neuropathic pain. Given the higher prevalence of pain disorders in females and their greater pain sensitivity, it is crucial to include women in pain and pain-management research.

For the purposes of this FOA, ORWH supports research on SCD pain at the intersection of sex, gender, race, ethnicity and biopsychosocial and cultural factors throughout the lifespan that affects the health of both women and men.

Integrating the purposeful accounting for sex as a biological variable (SABV) in biomedical research on SCD pain and pain management will fill gaps in our knowledge and inform more effective, personalized approaches to improve health for women and men. The 2019-2023 Trans-NIH Strategic Plan for the Health of Women is available on the ORWH website for additional guidance.

It is expected that the pragmatic trials supported under this RFA will recruit women in sufficient numbers to determine sex-specific responses as well as sex differences in trial outcomes. These comparisons have significant clinical relevance given the higher prevalence of pain in women. Studies should, as appropriate, enroll both sexes to better understand the influence of sex as a variable.

Additional Information

Applicants should review the NIH HEAL website at https://heal.nih.gov/funding/awarded and the Patient-Centered Outcomes Research Institute website https://www.pcori.org/research-results https://www.pcori.org/research-results to avoid submitting a trial that overlaps significantly with other on-going trials testing methods to manage pain.

This FOA may NOT be used for applications that propose testing of interventions to establish initial efficacy of drugs, devices or biologics for approval by the FDA (see instead other opportunities such as EPPIC-Net below). Applicants interested in conducting such trials are encouraged to contact an NIH Program Official of the scientifically appropriate NIH Institute or Center to discuss other FOAs for this purpose. Non-responsive applications will be withdrawn without review.

Types of Clinical Trials Not Responsive to this FOA

The following types of clinical trials are not responsive to this FOA and applications proposing such activities will be deemed non-responsive and will not be reviewed:

• Phase I (first-in-human) trials whether single or multi-site
• Single site trials
• Studies with the sole purpose to understand the mechanism of the intervention
• Studies to assess initial feasibility of an intervention
• Drug or device safety trial
• Studies that propose to conduct studies in animals or in vitro studies

Opportunities to Submit other Types of Pain Clinical Trials:

For further information on these programs see: https://www.painconsortium.nih.gov/Funding_Research/Funding_Opportunities

The Early Phase Pain Investigation Clinical Network (EPPIC-Net) will provide infrastructure for the rapid design and performance of high-quality Phase 2 clinical trials to test promising novel therapeutics for pain. This network will support exploratory clinical trials of investigational drugs and biologics, investigational devices, natural products, and surgical procedures for the treatment of pain. These trials may include deep phenotyping, validation of biomarkers, and proof of mechanism, to support justification and provide the data for designing a future Phase 3 trial. The specific pain conditions of interests for EPPIC -Net include well-defined conditions with high unmet therapeutic needs in patients across the lifespan. Further information can be found at HEAL Initiative: EPPIC-Net Pain Research Asset Application (OT2) (nih.gov)..

The Sickle Cell Disease Pain Management Trials Utilizing the Pain Management Effectiveness Research Network (SCD-ERN, RFA-AT-23-002 ) program will support multisite effectiveness clinical trials of pharmacologic, nonpharmacologic, and/or multicomponent approaches for acute and/or chronic SCD pain management, allowing continued opioid pain management when needed. However opioid medication use alone should not be the only intervention studied. Clinical trials will be conducted within the infrastructure of the HEAL ERN. Studies needing to randomize participants individually, collect in-person measures for research purposes (such as specified clinical laboratory tests, observed studies of mobility or other measures of function) or deliver an intervention in a standardized fashion should consider applying to the SCD-ERN Program.

Additional Information
Governance: The awards funded under this FOA will be cooperative agreements (see Section VI.2 Cooperative Agreement Terms and Conditions of Award). Close interaction with the NIH staff and with the CCC will be required to accomplish the goals of this program.

PRISM/Collaboratory Work Groups have been established by the CCC and the NIH as the core collaborative activity of this program. The Work Groups provide a forum for discussion of challenges and solutions across projects. Harmonized and standardized policies and processes will be vetted in these groups. Work Groups have been established in the following areas: Electronic Health Records, Regulatory /Ethics, Biostatistics & Study Design, Health Care Systems Interactions, Implementation Science, Health Equity, and Patient Reported Outcomes (http://rethinkingclinicaltrials.org/cores-and-working-groups/). Additional Work Groups may be identified as the PRISM/Collaboratory expands with new projects as part of this initiative. Work Groups will be comprised of individuals from each of the Projects, the Coordinating Center, and staff from the NIH. PD/PIs must identify study staff or investigators that will participate in PRISM/Collaboratory Work Groups.

A Steering Committee has been established by the CCC to address issues that span all projects, provide input into the policies and processes of the PRISM/Collaboratory, and assist in dissemination of policies and processes that enable research in healthcare systems, involving their patients, and practitioners. At a minimum, the Steering Committee will have one representative from each of the Projects, one representative from each Work Group, one representative from the Coordinating Center, NIH Program Officers and Project Scientists for the CCC and Projects. All members are expected to actively participate in all Steering Committee activities. The combined vote of NIH membership may never exceed 40 percent. NIH may convene an external panel of experts to provide advice on the overall program progress.

See Section VIII. Other Information for award authorities and regulations.

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

Section II. Award Information

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Local Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)

Federal Governments

• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their full SAM and Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

Key Personnel of the PRISM/Collaboratory Coordinating Center (funded under RFA-AT-19-011 or RFA-AT-22-002) must not be named as key personnel on applications submitted in response to this FOA.

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Martina Schmidt, Ph.D.
Telephone: 301-594-3456
Email: [email protected]

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

For this specific FOA, the Research Strategy section is limited to 30 pages, divided between the UG3 and UH3 phases of the project.

Instructions for Application Submission

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

SF424(R&R) Cover

All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

The application should provide sufficient rationale for the proposed HCS(s) for the Project. Applicants should provide a description of successfully conducted clinical studies within the partnering HCS, and describe the infrastructure and expertise (e.g., clinical investigators, informaticists) to implement the proposed pragmatic trial within all proposed HCSs.

SF424(R&R) Senior/Key Person Profile

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Biosketches should reflect the PD(s)/PI(s) and key personnel's expertise in design and conduct of large-scale clinical or implementation trials within multiple HCS including using electronic health records for recruitment and outcomes assessment. The experience of the investigative team with successful recruitment and retention of participants should be described.

R&R Budget

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Budgets for both phases (UG3/UH3) must be included; the UH3 budget will undergo reassessment during the UG3 planning phase.

Minimum effort of personnel: The PD/PI must devote a minimum level of effort of 20% annually (2.4 -person months) to the project. There should be an appropriate mix of time allocated for senior and junior scientists to ensure the successful conduct of the study. Budgeted effort of other personnel should be appropriate to the needs of the project. The budget should include personnel at all participating HCS with expertise relevant to the project, which might include a health informatics expert, clinical investigators, and staff with expertise in the administrative aspects of clinical trials oversight.

Applications should budget for study personnel to participate in each of the Work Groups.

Applications must budget for project PD(s)/PI(s) travel to attend two, one-and-a-half-day PRISM/Collaboratory program meetings in the first year, and an annual meeting in subsequent years in the greater Washington D.C. area. In addition, applicants must budget for one PD/PI to attend the annual HEAL Investigators Meeting in the greater Washington D.C. area.

R&R Subaward Budget

All instructions in the SF424 (R&R) Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the SF424 (R&R) Application Guide must be followed.

PHS 398 Research Plan

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

To clearly distinguish between the two phases, applicants should specify separate UG3 and UH3 information in each subsection (Specific Aims and Research Strategy) of the PHS 398 Research Plan as appropriate. Activities in both phases will depend on the specific study (e.g., type of interventions, experimental design, randomization strategy and proposed outcome measures). In preparing the application, investigators should consider the fact that applications will be assigned a single impact score for both UG3 and UH3 phases.

Specific Aims: Applicants should address the scientific questions to be answered, what specifically will be done during the proposed funding periods and the impact of addressing the research question on public health. Specific aims should be scientifically appropriate for the distinct phases of the project. Include separate aims, within the designated page limit, for both the UG3 and UH3 phase, and clearly label them as UG3 specific aims and UH3 specific aims.

Research Strategy: Within the Research Strategy, applicants should first describe the UG3 Phase and then the UH3 Phase. The Research Strategy section should have a clear demarcation of the UG3 and UH3 phases of the application. It is not necessary to repeat background information or details of methods in the UH3 portion that were provided in the UG3 portion. Applications proposing a 2-year UG3 Phase must propose and justify the need for a vanguard pilot study that will inform the design of the UH3 Phase. If a vanguard pilot study is proposed in the UG3 phase, the approach must detail a strong rationale for the pilot work, the study methods, and specific milestones for defining success. Only minor adaptations to existing interventions should be proposed in this pilot work. The UH3 Phase must be described in sufficient detail to permit reviewers to assess significance and innovation of the proposed work and the strength of the experimental design. Address how the research question serves the goals of the overall PRISM program and addresses the urgent need for better pain management. Applications should describe details for the proposed pragmatic trial or implementation research study including projections for recruitment, attrition, and effect size estimations. Investigators are encouraged to describe how the approaches, measures, design, and outcomes proposed are pragmatic or utilize implementation research methods.

If the project proposes to implement evidence-based guidelines, applicants are encouraged to describe the quality and level of evidence for the treatments that will be implemented from the guidelines.

The application should describe the health care system partners and the investigative team's experience conducting pragmatic trials within health care systems. In general, all studies must use multiple HCS for implementation, unless a specific rationale for limiting this aspect of the project is provided, which must be identified in the application. The application must provide a rationale for the HCS selected for the Project and provide a description of the infrastructure and expertise to implement the proposed pragmatic trial within all proposed HCS.

Both the UG3 and the UH3 phases of the Research Strategy must include a summary of the proposed Milestones Plan that is a required Other Clinical Trial-related attachment. The summary should describe the key milestones that need to be met for each phase of the application (UG3 and UH3) to ensure its success; the methods that will be used to reach the milestones; and a timetable identifying when each of these key milestones will be met.

PRISM/Collaboratory Work Groups include participation by individuals from all funded Projects, the CCC, and the NIH. Applicants should describe how project personnel would participate in the PRISM/Collaboratory Work Groups (Electronic Health Records, Regulatory /Ethics, Biostatistics & Study Design, Health Care Systems Interactions, and Patient Reported Outcomes (http://rethinkingclinicaltrials.org/cores-and-working-groups/). Applicants must describe their willingness to comply with policies, guidelines and practices developed by the Work Groups, and to work with the CCC in providing relevant information and materials.

Applicants should not propose work that duplicates efforts already funded or underway (https://reporter.nih.gov/, https://heal.nih.gov/funding/awarded, https://www.pcori.org/explore-our-portfolio). Although novel theoretical approaches and methodologies may be needed, when possible, applicants should leverage, adopt or adapt resources from ongoing NIH-supported efforts in informatics as well as other national efforts including but not limited to the many federal investments in the HMO Research Network, the CTSAs, REDCap, PROMIS, NIH Toolbox, Health Care Innovation Awards, DEcIDE, eMERGE, other networks, CERTs, SHARP, Vaccine Safety Datalink, PCORI, the Sentinel Initiative.

Applicants should allow flexibility in determining which patient-reported outcome measures will be used, if possible. The HEAL Initiative has a set of Common Data Elements that includes required or highly recommended measures for collection at baseline and primary follow-up timepoint (https://heal.nih.gov/data/common-data-elements).

Letters of Support

Applications must include a strong letter of support from each of the HCS partners that relates their commitment to the proposed research and outlines how the project fits with organizational priorities, the quality of the proposed EHR and data systems and the commitment of their IT staff to the project. The letter must provide a description of how the project would directly impact delivery of healthcare within their organization and indicate level of intention to sustain the intervention(s) based upon results. The application is expected to include letters from the officials responsible for intellectual property issues at the applicant institutions (including sub-contractor institutions) stating that the institution supports and agrees to abide by the Data Sharing Plan put forth in the application. These letters should be clear expressions of commitment consistent with achieving the goals of the program.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

The following modifications also apply:

HEAL Data Sharing

NIH intends to maximize the impact of HEAL Initiative-supported projects through broad and rapid data sharing. Consistent with the HEAL Initiative Public Access and Data Sharing Policy (https://heal.nih.gov/about/public-access-data), all applications, regardless of the amount of direct costs requested for any one year, are required to include a Data Management and Sharing Plan outlining how scientific data and any accompanying metadata will be managed and shared. The plan should describe data types, file formats, submission timelines, and standards used in collecting or processing the data. It is expected that data generated by HEAL Initiative-funded projects will be submitted to study-appropriate domain-specific or generalist repositories in consultation with the HEAL Data Stewardship Group to ensure the data is accessible via the HEAL Initiative Data Ecosystem.

To maximize discoverability and value of HEAL datasets and studies, and facilitate data integration and collaboration, applications submitted in response to this FOA are strongly encouraged to incorporate standards and resources where applicable:

The NIH notices referenced below provide additional NIH guidance that should be considered in developing a strong data management and sharing plan. The list is instructive but not comprehensive.

Recipients conducting research that includes collection of genomic data should incorporate requirements under the NIH Genomic Data Sharing Policy (NOT-OD-14-124, NOT-OD-15-086).

• Applicants are encouraged to ensure that data collected by the study conform to Findable, Accessible, Interoperable, and Reusable (FAIR) principles.
• Applicants are specifically encouraged to incorporate into their planning, an alignment with the guidelines, principles and recommendations developed by the HEAL Data Ecosystem, including but not limited to preparing data to store in selected specified repositories, applying minimal metadata standards, use of core HEAL Clinical Data Elements (CDEs, https://heal.nih.gov/data/common-data-elements), and other necessary requirements to prepare data to connect to the HEAL Data Ecosystem.
• All new HEAL clinical pain studies are required to submit their case-report forms/questionnaires to the HEAL Clinical Data Elements (CDE) Program. The program will create the CDE files containing standardized variable names, responses, coding, and other information. The program will also format the case-report forms in a standardized way that is compliant with accessibility standards under Section 508 of the Rehabilitation Act of 1973 (29 U.S.C 794 (d)), which require[s] Federal agencies to make their electronic and information technology accessible to people with disabilities. HEAL Initiative clinical studies that are using copyrighted questionaries are required to obtain licenses for use prior to initiating data collection. Licenses must be shared with the HEAL CDE team and the program officer prior to use of copyrighted materials. For additional information, visit the HEAL CDE Program.
• Elements of an NIH Data Management and Sharing Plan (NOT-OD-21-014)
• NIH has provided guidance around selecting a repository for data generated by NIH-supported research and has developed desirable characteristics for all data repositories (NOT-OD-21-016).
• NIH encourages the use of data standards including the PhenX Toolkit (www.phenxtoolkit.org) (for example, see NOT-DA-12-008, NOT-MH-15-009).
• NIH encourages researchers to explore the use of the HL7 FHIR (Fast Healthcare Interoperability Resources) standard to capture, integrate, and exchange clinical data for research purposes and to enhance capabilities to share research data (NOT-OD-19-122). The FHIR standard may be particularly useful in facilitating the flow of data with EHR-based datasets, tools, and applications.
• NIH encourages clinical research programs and researchers to adopt and use the standardized set of data classes, data elements, and associated vocabulary standards specified in the United States Core Data for Interoperability (USCDI) standards, as they are applicable (NOT-OD-20-146). Use of the USCDI can complement the FHIR standard and enable researchers to leverage structured EHR data for research and enable discovery.
• Recipients conducting research that includes collection of genomic data should incorporate requirements under the NIH Genomic Data Sharing Policy (NOT-OD-14-124, NOT-OD-15-086).

Appendix:

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

• No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

If the application includes human subjects, it must include at least one human subjects study record for the activities of the UH3 project. If the UG3 will include any human subjects research a separate study record should be included for the UG3 human study or studies. As stated in the instructions, investigators must submit a study record for each clinical trial proposed in the application.

Section 2 - Study Population Characteristics

2.5 Recruitment and Retention Plan
Describe the following: 1) the planned recruitment methods including use of contact lists (participants and/or sites) databases or other pre-screening resources, advertisements, outreach, media / social media and referral networks or groups; 2) if there are known participant or study-related barriers to accrual or participation (based on literature or prior experience), please list these barriers and describe plans to address them to optimize success; 3) contingency plans for participant accrual if enrollment significantly lags behind accrual benchmarks; 4) participant retention and adherence strategies; and 5) possible competition from other trials for study participants.

Applicants must provide strong evidence of the availability of appropriate institutional resources, and suitable patient populations, providers, clinics, or facilities (depending on unit of randomization). Documentation of availability of eligible participants, clinic sites, or units of randomization, presented in tabular format must be provided. The application must include relevant information that addresses the feasibility of recruiting participants who are eligible for the pragmatic trial implementation study. Specifically, applicants must provide evidence that each recruiting center in the study or trial has access to a sufficient number of participants who meet the eligibility criteria as defined in the submitted protocol. For multisite applications, information must be provided for each participating site.

2.7 Study Timeline
Include a table or graph of the overall study timeline. This is expected to be a visual representation (such as a Gantt chart) of core milestones and key project management activities. A narrative is not expected in this section.

The study timeline should include core milestones that need to be met throughout the lifecycle of the clinical trial (to include both the UG3 and UH3 phases) to ensure its success, and the subtasks that will be used to reach the milestones. In the timeline, the study duration is expected to be displayed in months. The timeline should include, but is not limited to, the following:

(a) When any vanguard study will be open to enrollment and when specific milestones for defining success will be met (if applicable)

(b) When the UH3 study opens to enrollment
(b) When core milestones (see below) are met
(c) What subtasks are needed to reach the core milestones
(d) When final transfer of the data will occur
(e) When analysis of the study data will occur
(f) When the primary study manuscript will be submitted for publication

Section 3 - Protection and Monitoring Plans

3.3 Data and Safety Monitoring Plan
In addition to the NIH application requirements for a data and safety monitoring plan for clinical trials, Applicants should refer to NIH’s policy on data and safety monitoring (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html).

Section 4 - Protocol Synopsis

4.1.a. Detailed Description
Describe the protocol to be followed in each arm of the trial. Include a brief description of how the trial will standardize the intervention and whether there are any plans to intervene to improve adherence to the intervention at the sites. Specify concomitant interventions, if applicable. Describe the proposed experimental design, including a discussion of the clinical trial design and the rationale for the design chosen (pragmatic, explanatory, cluster-randomized, adaptive, etc.).

Section 5 - Other Clinical Trial-related Attachments

5.1 Other Clinical Trial-related Attachments
The following attachments must be included as a part of the cooperative agreement application. Attachments permit expansion of certain elements that cannot be appropriately described in the Research Strategy. All attachments listed below must be provided or the application will not be peer reviewed.

1. Clinical Trial Experience
Applicants must provide a detailed table listing the characteristics of trials that demonstrate Key Personnel experience in trial or implementation study coordination in the last 5 years. The table must be provided as an attachment called "Clinical Trial Experience.pdf", appended with 1, 2, 3, etc. as needed, and must not exceed 3 pages.

The table columns should include:

• Clinical trial or implementation study title
• Applicant's role in the trial
• A brief description of the trial design
• Planned enrollment
• Actual enrollment
• Number of sites
• Whether the trial(s) were completed on schedule or not
• Publication reference(s)

2. Milestones Plan
A Milestones Plan must be provided as an attachment called "Milestones Plan.pdf", appended with 1, 2, 3, etc. as needed, and must not exceed 3 pages.

The milestones should be well described, quantifiable, and scientifically justified to allow an assessment of progress. For UG3 milestones, applicants should delineate what they propose to achieve to proceed to the UH3 phase. The milestones should also include a timeline, a discussion of the suitability of the milestones for assessing success in the UG3 Phase, and a discussion of the implications of successful completion of these milestones for the proposed UH3 Phase. Annual milestones for the Project implementation (UH3) phase should also be included in the application, although it is understood that timelines and milestones for implementation in the UH3 phase that are proposed in the application will evolve as activities in the UG3 phase progress, if an Award is made.

All applicants must use the following definition of a milestone in their application: a scheduled event in the project timeline that signifies the completion of a major project stage or activity. Milestones must be relevant, achievable, and measurable. Milestones should address overall recruitment and retention goals. The Terms and Conditions under this FOA will include a milestone plan that is mutually agreed upon by the investigators and NIH.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

PHS Assignment Request Form

All instructions in the SF424 (R&R) Application Guide must be followed.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov.

4. Submission Dates and Times

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

To expedite review, applicants are requested to notify Dr. Martina Schmidt in the NCCIH Referral Office by email at [email protected] when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

All post-submission materials must be received by the Scientific Review Officer (SRO) no later than 30 calendar days prior to the peer review meeting. In addition to the NIH policy for allowed post-submission materials in NOT-OD-19-083, the following post-submission materials are allowed:

• Updated Clinical Trial Experience Table (e.g., due to updated enrollment numbers, publication of trial results, or newly started clinical trials)
• Updated Milestones Plan (e.g., due to the hiring, replacement, or loss of an investigator; change to health care systems participating in the trial; or change in electronic health record or IT infrastructure)

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

For this announcement, note the following: This FOA includes Additional Review Criteria on Milestones, which require comment by reviewers, and which are to be considered when determining the overall impact score.

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NCCIH, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Council for Complementary and Integrative Health (NACCIH). The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain applicable clinical trials on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

• Federalwide Research Terms and Conditions
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex (including gender identity, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.

• Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov.

• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including reasonable accommodations and making services accessible to them, see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.

• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.
  
• For guidance on administering programs in compliance with applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 and 2 CFR Part 200.206 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 75, 2 CFR Part 200 and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an acquisition mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

• Overseeing the overall budget, activities, and performance of the Project. The PD(s)/PI(s) must devote a minimum level of effort of 20% annually (2.4 calendar months) to the project. If a project includes multiple PIs, the total annual PI effort must be at least 20%. The institution must obtain appropriate prior approval for any change in PI effort.
• Accepting the participatory and cooperative nature of the collaborative research process and complying with policies and practices developed by the NIH PRISM/ Collaboratory governing structure.
• Sharing data and resources according to the approved sharing policies for the PRISM/ Collaboratory program and the NIH HEAL Initiative Public Access and Data Sharing requirements (https://heal.nih.gov/about/public-access-data)..
• Participating in all meetings of the PRISM/Collaboratory Steering Committee. Identifying study team members with relevant expertise to participate in program-wide Work Groups and sub-committees (as appropriate).
• Cooperating with the PRISM/Collaboratory Steering Committee, Collaboratory Coordinating Center, research partners, and NIH staff in the design and conduct of protocols, analysis of data, and reporting of results of research.
• Agreeing to accept close coordination, cooperation, and management of the project with NIH, including those outlined below under "NIH Responsibilities."
• Submitting materials to the NIH Program Director, Coordinating Center, and/or Steering Committee as requested. This will include regular reports of accomplishments and roadblocks, conference and meeting summaries, and other reports as requested.
• Materials submitted will meet all subject and formatting requirements.
• Recipients will submit a detailed transition request for the UH3 Project implementation phase, outlining UG3 progress, how negotiated UG3 Milestones have been met, as well as detailed plans, budget, and annual milestones for the UH3 implementation phase. Note that, funding of the UG3 Project planning phase cooperative agreement does not guarantee support of the UH3 Project implementation phase
• Any of the above function may be performed by the applicant organization or by subcontract to the applicant organization
• Recipients(s) will retain custody of and have primary rights to the data and software developed under these awards, subject to Government policies regarding rights of access consistent with current DHHS, PHS, and NIH policies.

NIH staff has substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

• The NIH Project Scientist will work with the PD(s)/PI(s) and the Steering Committee to ensure the objectives of the program are being met. The primary responsibility for the program resides with the recipient, although specific tasks and activities will be shared among the recipient and the NIH Project Scientist.
• NIH staff will interact with the PD(s)/PI(s) on a regular basis to monitor progress. Monitoring may include regular communication with the PD(s)/PI(S) and his/her staff, periodic site visits for discussion with the recipients research team, observation of field data collection and management techniques, fiscal reviews, and other relevant stewardship activities.
• The NIH reserves the right to terminate or curtail the award (or an individual component of the award) in the event of inadequate progress or data reporting).
• Additional NIH staff may participate in all Work Groups, implementation teams, and committees, including the Steering Committee, as appropriate. NIH may designate staff from other federal agencies to participate, if advantageous to facilitate the activities of the program.
• NIH staff will act as a resource and facilitator for activities of the recipient with non-NIH HCS researchers and other NIH, DHHS, or other federally-sponsored research networks that may be relevant to this effort.
• NIH staff will provide input, expert advice, and suggestions in the design, development, and coordination of the infrastructure development and implementation efforts.
• NIH staff will report periodically on the progress of the program to the NIH Common Fund, NIH, and Departmental leaders. NIH may convene an external panel of experts to provide advice on program progress.
• NIH staff will conduct an administrative review of the UH3 transition request to determine whether the project will transition to UH3 funding and be implemented. Criteria for transition to the UH3 phase used in the NIH administrative review include: successful achievement of the UG3 milestones, potential for successfully meeting the UH3 implementation phase plans and milestones, demonstrated the ability of the team to work within the consortium arrangement and the availability of funds.
• Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice

Areas of Joint Responsibility include:

• Ensuring that NIH HCS sites and investigators, as well as NIH and other research partners, fully comply with federal regulatory requirements. This includes but is not limited to those relating to human subjects protections, informed consent, and reporting of adverse events.
• Jointly developing appropriate confidentiality procedures for data collection, processing, storage, and analysis to ensure the confidentiality of data on individual health care provider organization patients, health care providers, and other institutions involved in any PRISM/Collaboratory research projects.
• Participating in the PRISM/Collaboratory Steering Committee to address issues that span all projects, provide input into the policies and processes of the PRISM/ Collaboratory, and assist in the dissemination of policies and processes that enable research in partnership with health care systems, their patients, and practitioners. At a minimum, the Steering Committee will be composed of one representative from each of the Projects, one representative from each Work Group, one representative from the CCC, the NIH Program Coordinator, and representatives from various NIH ICs and the Common Fund. The combined vote of NIH membership may never exceed 40 percent of the total committee membership.
• Participating in the PRISM/ Collaboratory Work Groups that have been established as the core collaborative activity of this program. The Work Groups provide a forum for discussion of challenges and solutions across projects; harmonized and standardized policies and processes will be vetted in these groups. Work Groups have been established in the following areas: Electronic Health Records, Regulatory /Ethics, Biostatistics & Study Design, Health Care Systems Interactions, and Patient-Reported Outcomes (http://rethinkingclinicaltrials.org/cores-and-working-groups/). Additional Work Groups may be identified as the PRISM/ Collaboratory expands with new projects. Work Groups are open to participation by individuals from all funded Projects, the CCC, and the NIH.
• Recipients will work with other PRISM/Collaboratory investigators and NIH to identify common clinical outcome measures (such as measures of quality of life, physical function, pain, or fatigue). NIH and CCC staff will work with the Principal Investigators to facilitate this aspect of the Projects.
• Establishing and adherence by each Project Team (Project grantee, CCC grantee, and NIH staff) to a written plan of engagement, with timelines, to ensure timely delivery of the tested implementation plan.
• Working together with the CCC through all phases of the projects, including the implementation and close out, to assure all resources, materials, protocols, data, best practices, program policies, and lessons learned are disseminated broadly through the CCC, to inform researchers and health care systems engaged in research in health care settings.

Dispute Resolution:
Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

3. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over the threshold. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 and 2 CFR Part 200 Award Term and Condition for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Sekai Chideya-Chihota
National Center for Complementary and Integrative Health (NCCIH)
Phone: 240-552-2994
Email: [email protected]

Priscah Mujuru
National Institute on Minority Health and Health Disparities (NIMHD)
Phone: 301-594-9765
E-mail: [email protected]

Karen A. Kehl, PhD, RN
National Institute of Nursing Research
Telephone: 301-594-8010
Email: [email protected]

Elena K Gorodetsky, M.D., Ph.D.
Office of Research on Women's Health (ORWH)
Phone: (301) 594-9004
E-mail: [email protected]

Susan Shero
National Heart, Lung, and Blood Institute (NHLBI)
Phone: none
E-mail: [email protected]

Charles H Washabaugh, PhD
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Phone: 301-496-9568
E-mail: [email protected]

Houmam H Araj
National Eye Institute (NEI)
Phone: (301) 435-8166
E-mail: [email protected]

Martina Schmidt, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-594-3456
Email: [email protected]

Debbie Chen
National Center for Complementary and Integrative Health (NCCIH)
Phone: 301-594-3788
Email: [email protected]

Priscilla Grant
National Institute on Minority Health and Health Disparities (NIMHD)
Phone: 301-594-8412
E-mail: [email protected]

Kelli Oster
National Institute of Nursing Research (NINR)
Telephone: 301-594-2177
Email: [email protected]

Nina Hall
National Heart, Lung, and Blood Institute (NHLBI)
Phone: 301-435-0710
E-mail: [email protected]

Sahar Rais-Danai
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Phone: 301-594-5032
E-mail: [email protected]

Karen Robinsonsmith
National Eye Institute (NEI)
Phone: (301) 451-2020
E-mail: [email protected]

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75 and 2 CFR Part 200.