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.

No late applications will be accepted for this Notice of Funding Opportunity (NOFO).

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the How to Apply - Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the How to Apply - Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the How to Apply - Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

1. Use the NIH ASSIST system to prepare, submit and track your application online.
2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.
   
   
3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.



Table of Contents
Part 1. Overview Information
Key Dates
Part 2. Full Text of Announcement
Section I. Notice of Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Background

The NIH HEAL Initiative: This notice of funding opportunity (NOFO) is part of the Helping to End Addiction Long-term^® Initiative, or NIH 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 initiative is available at https://heal.nih.gov/.

Since 2001, more than 2.77 million U.S. troops have been deployed for Operation Enduring Freedom in Afghanistan and Operation Iraqi Freedom and Operation New Dawn in Iraq. The all-volunteer military experienced multiple redeployments to the war zone and extensive use of the reserve components of the military and National Guard, that also involved the deployment of women and parents of young children. Many of these deployed service members sustained severe injuries that in previous wars would have resulted in death. Significant and continuing improvements in outer tactical vests (body armor) and helmets have saved lives. However, despite these improvements, many service members returning from these operations and from other military operations experienced pain, traumatic brain injuries (TBIs), symptoms of post-traumatic stress disorder (PTSD), suicidal thoughts or behaviors, substance abuse, and/or related comorbidities. Studies report nearly 45 percent of active-duty service members and 50 percent of Veterans experience pain on a regular basis, and there is significant overlap among chronic pain, PTSD, and persistent post-concussive symptoms. There is an ongoing challenge with pain among military and Veteran populations and an incomplete evidence base for effective pain management. Opioid medications continue to be prescribed for the treatment of chronic pain despite the association of chronic opioid use with the potential for misuse, and they often fail to adequately control pain. As a result, there continues to be a need for additional nonopioid approaches to complement or replace opioid-based strategies for pain management and to reduce the needs and risks associated with excessive reliance on opioids.

In June 2011, the Institute of Medicine (IOM) released a Consensus Report, Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research. The report notes that chronic pain affects an estimated 116 million American adults— more than the total affected by heart disease, cancer, and diabetes combined. Pain also costs the nation up to $635 billion each year in medical treatment and lost productivity. The report notes that ideally, most patients with severe persistent pain would obtain pain care from an interdisciplinary team using an integrated approach that would target multiple dimensions of the chronic pain experience including disease management, reduction in pain severity, and improved functioning, emotional well-being, and health-related quality of life. The NIH, the U.S. Department of Defense (DOD), and the U.S. Department of Veterans Affairs (VA) have been working individually and collaboratively to develop and improve pain management approaches for military personnel, Veterans, and their families. In 2014, NCCIH partnered with the National Institute on Drug Abuse (NIDA) and the VA to fund 13 grants to research military and Veteran health with a focus on nonopioid approaches to pain and related conditions. This important partnership was expanded in 2017 to include the DOD and additional components of NIH [National Institute on Alcohol Abuse and Alcoholism (NIAAA), Eucine Kenney Shriver National Institute of Child Health and Human Development (NICHD), National Institute on Drug Abuse (NIDA), National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Nursing Research (NINR), and Office of Research on Women's Health (ORWH)] to initiate the NIH-DOD-VA Pain Management Collaboratory (PMC). The  PMC r supported 11 research projects focused on the development and testing of nonopioid approaches to pain management (RFA-AT-17-001) along with a coordinating center (RFA-AT-17-002) to support the program. A twelfth research project was funded in FY22 and a thirteenth in FY23 (RFA-AT-22-006).

Military and Veteran health care systems (HCS) and other HCS that provide services to military personnel, Veterans, and their families are the paradigmatic research platforms for this program. Research conducted in partnership with eligible VA and DOD health care providers is essential for obtaining meaningful and relevant research results in real world health care delivery systems serving veterans and military service members.

Team-based integrative care is increasingly recognized as a fundamental effective aspect of HCS. Team-based care is defined as an interprofessional, multidisciplinary team approach to patient-centered care coordinated across a variety of systems. The National Academy of Medicine (formerly known as the Institute of Medicine) predicts team-based care models will significantly reduce health care costs, saving an estimated $240 billion annually in national health care expenditures.

Despite the recognized and compelling need for research to identify and implement effective complementary nonopioid approaches for management of pain and comorbid conditions in military and Veteran populations, many challenges exist. Ethical and regulatory issues must be addressed to perform research in health care delivery settings. Health care providers focus on providing the best treatment, based on current knowledge, whereas research typically focuses on studying which treatments work best in a precisely defined population. Further, multiple challenges remain in identifying the best strategies to successfully integrate evidence-based interventions within specific health care settings.  For example, research studies frequently use study endpoints that are not part of routine patient care and results may suggest adoption of interventions that are challenging to deliver.  . Bridging the gap between research and practice is an important step in the direction of providing increased effective treatment options to patients.

Pain is a subjective experience impacted by a variety of biological, psychological, and social factors. Moreover, pain rarely occurs in isolation and is often accompanied by comorbid conditions or multiple pain conditions, as well as mental health disorders such as anxiety and depression. The multifaceted nature of pain necessitates a multifaceted, interdisciplinary approach in its treatment that is by definition complex, involving multiple domains spanning an individual’s physiology, emotional well-being, environment, and social connection. Models of pain management that focus mainly on physiological systems are incomplete and fall short of accessing the full potential of human health and healing, and health restoration. Recognizing the importance of a multi-domain approach to health care, the DOD, the VA, and NCCIH have each developed programs or strategic plans that address health through multiple domains, namely, Total Force Fitness (DOD), Move to Health (DOD), Whole Health (VA), and Whole Person Health (NCCIH). These initiatives share a common principle that health and health restoration are most effectively achieved through addressing the whole person, not just the disease. A recent report by the National Academies of Sciences, Engineering, and Medicine highlights the need for a whole person health approach to medicine that emphasizes greater focus on promoting health, rather than reacting only to disease. A whole person health approach that encompasses the full spectrum of health and social needs of Veterans, service members, and their families could have a profound impact on pain management by addressing what is most important to the individual in treating not just the pain, but also the comorbidities that so often occur with pain. It is also important to note the well-documented racial and ethnic disparities in both the experience and in the treatment of pain. Pain disproportionately impacts African American and Hispanic adults and those of low socioeconomic status. Compounded with findings that individuals from racial and ethnic minority groups receive less analgesics for their pain compared to White persons, a whole person approach to health has the potential to bridge the pain management divide for individuals from racial and ethnic minority groups by taking into account all the factors that affect physical, emotional, social, and spiritual well-being.

Purpose

The purpose of this NOFO is to solicit UG3/UH3 phased cooperative agreement research applications to conduct efficient, large-scale pragmatic clinical trials and/or implementation science demonstration projects within the infrastructure of the  PMC that focus on nonopioid approaches to management of pain and other comorbid conditions, including complementary and integrative approaches used alone or in combination with standard care (e.g., mindfulness meditation combined with standard pharmaceutical treatment), and improving prevention and treatment for opioid misuse and addiction in U.S. military personnel, Veterans, and their families. The PMC has established a coordinating center that provides national leadership and technical expertise for all aspects of HCS-focused research including assistance to UG3/UH3 grant recipients.

Applications submitted under this NOFO are expected to:

• Support the design and execution of additional high-impact demonstration projects that will conduct pragmatic clinical trials focusing on effectiveness research, implementation research, or hybrid effectiveness-implementation research on nonopioid approaches for the management of pain and comorbidities with patients in health care delivery systems that provide care to veterans, military personnel, and their families.
• Make available data, tools, best practices, and resources that will facilitate a research partnership with health care delivery systems that provide care to veterans, military personnel, and/or their families.

Research projects funded through this NOFO will be expected to work with the Pain Management Collaboratory Coordinating Center (PMC3) and the other funded PMC projects. This includes participation in PMC3 work groups, working with  PMC3 on detailed plans for site implementation, determining resource needs, testing data extraction methods, developing plans for all aspects of ethical and regulatory oversight/protection of human subjects, and integrating data using common data elements (CDEs) within the NIH HEAL Initiative CDE repository to increase the overall impact of findings.

Awards made under this NOFO will initially support a 1-year milestone-driven research planning phase (UG3), with possible transition to a pragmatic trial and/or implementation science demonstration project research execution phase (UH3; 2–4 years). UG3 projects that have met the scientific milestone and feasibility requirements may transition to the UH3 phase following administrative review by the respective funding agency. The UG3/UH3 application must be submitted as a single application, following the instructions described in this NOFO.

Research Objectives

All demonstration projects should address a research question important to the health of U.S. Veterans, military personnel, and their families that is focused on nonopioid  approaches to the management of pain and, if applicable, co-occurring conditions. The demonstration project may provide a definitive test of the underlying question to assess intervention effectiveness or carry out implementation research (or hybrid effectiveness-implementation research). Applications that include effectiveness research aims should be guided by the Pragmatic-Explanatory Continuum Indicator Summary 2 tool (PRECIS-2) and use more pragmatic approaches rather than explanatory ones when appropriate to address the proposed hypothesis (PRECIS-2 is described in https://www.bmj.com/content/350/bmj.h2147).

We define pragmatic trials as trials primarily designed to determine the effects of an intervention under the usual conditions in which it will be applied, in contrast with explanatory trials, which are primarily designed to determine the effects of an intervention under ideal circumstances. Efficacy research involves strict limitations on who may participate to minimize error, bias, and confounding. The emphasis on internal validity enhances confidence in interpreting positive results as indicating a causal relationship between the intervention(s) and outcome(s). Effectiveness research is designed to test interventions of known efficacy in real-world settings with an emphasis on external validity, that is, whether the results can be applied to a definable group of patients in a particular clinical setting in routine practice (i.e., generalizability). In effectiveness research, limitations on who may participate are minimized in order to maximize the likelihood that study participants and the population intended to benefit from the interventions are similar. Dissemination research is the scientific study of targeted distribution of information and intervention materials to a specific public health or clinical practice audience, while implementation science is the scientific study of the use of strategies to adopt and integrate evidence-based health interventions into clinical and community settings to improve patient outcomes and benefit population health. For the purposes of this NOFO, only effectiveness research, implementation science, and hybrid effectiveness-implementation trials will be responsive. Dissemination may be included as an aim, but applications that only propose dissemination research will be considered nonresponsive.

The research question(s) proposed should be of major public health importance, focusing on nonopioid approaches to the management of pain and comorbid conditions in Veterans, military personnel, and one that will engage partnership with health care delivery systems providing services to this population. Although trials will likely be conducted in the VA and DOD health care systems, it is expected that many of the findings will be generalizable to practices across the broader health care community. The NIH HEAL Initiative prioritizes speeding scientific solutions to stem the national opioid public health crisis, and developing nonopioid approaches to pain management and co-occurring conditions remains integral to improving prevention and treatment of opioid misuse and addiction. The unique challenges to service member and Veteran health represent an opportunity to conduct pragmatic clinical trial research to identify what approaches to pain management are effective when delivered in the VA and DOD health care settings. Of special interest are effectiveness trials of approaches that have not yet been evaluated for effectiveness in the VA and/or DOD health care settings. Applicants are strongly encouraged to review the PMC website to avoid submitting a trial that overlaps significantly with other ongoing or completed PMC trials. For example, investigators should avoid overlap with approaches being evaluated in ongoing PMC trials, including remotely delivered cognitive behavioral therapy, remotely delivered mindfulness, chiropractic care dose optimization, a Screening, Brief Intervention, and Referral to Treatment for Pain Management (SBIRT) approach, percutaneous peripheral nerve stimulation, and several multi-modal coordinated care pathways. Prior to submitting to this NOFO, applicants are encouraged to speak with the NCCIH scientific/research contact person. The NIH RePORTER website at https://reporter.nih.gov, the DOD Defense Technical Information Center website at https://discover.dtic.mil, and the Patient-Centered Outcomes Research Institute website at https://www.pcori.org/ should also be reviewed to avoid submitting a trial that overlaps significantly with other ongoing or completed trials testing methods to manage pain in U.S. Veterans, military personnel, and their families. In addition, integrated models of multicomponent care that are delivered in different settings (e.g., pain care that could include collaborative care, care management, care delivered through tele-care, peer coaches, or informal caregivers) will be of higher programmatic priority.

Research projects should be performed within large HCS that use electronic health records (EHRs) to leverage data collection that occurs in health care delivery rather than requiring independent research data collection. The HCS partnerships must be able to facilitate access to all data sources relevant to the project, which may include inpatient, outpatient, clinical laboratory, and pharmacy data. Applicants, who may be from academic institutions or other organizations, must have demonstrated success in conducting clinical research in partnerships with HCS serving military or Veterans. Interdisciplinary teams should include necessary expertise to conduct the trial such as military researchers on military-focused applications and VA researchers on Veteran-focused applications. Applicants should involve appropriate HCS personnel when conducting the pragmatic clinical trial. . Applicants must document the commitment of the health care organization to the project and  must include letters of support from the HCS partners that relate their commitment to the proposed research and outline how the project fits with organizational priorities

For this NOFO, multisite clinical trials are defined as trials that enroll from at least three recruitment sites that are geographically distinct and non-overlapping with respect to the population of patients engaging with services and are likely to be compliant with NIH policy on the inclusion of women and minorities as subjects in clinical research, as well as individuals across the lifespan (https://grants.nih.gov/policy/inclusion/women-and-minorities.htm and https://grants.nih.gov/policy/inclusion/lifespan.htm),. Two sites will be permitted if there is a strong justification for how fewer sites can still achieve generalizability and and be sufficient for valid analysis of the data. Multiple sites are necessary in efficacy trials to increase generalizability of findings and ensure appropriate size and diversity of eligible participants. 

For projects proposing effectiveness aims:

Outcomes should include assessing pain and pain reduction, pain interference, ability to function in daily life, quality of life, and medication usage/reduction/discontinuation. Additional outcomes may focus on assessing conditions co-occurring with high frequency in this population. There is also interest in obtaining objective sensor-based measures that provide data on people’s daily activities to gain a better understanding of the relationship between ratings of pain and functional changes.

When testing effectiveness, projects are encouraged to enroll participants based on broad eligibility criteria to maximize generalizability, with minimum exclusions based on risk, age, health literacy, comorbidities, or expected adherence. Studies should enroll from the target populations the interventions are intended to benefit, namely Veterans, active-duty service members, and their beneficiaries. It is important that women are represented according to their proportion of the population being studied, preferably overrepresented, and that studies include a comparative analysis of differential effects between men and women.

Projects aimed at evaluating team-based care models should determine overall effectiveness of team-based care compared to conventional, non-team-based primary care. Secondary outcomes may assess differential benefits contributed by unique components of the team-based care package. 

In some cases, a stepped-wedge design may be the only practical way to generate the appropriate data. Nevertheless, considering the practical, ethical, and analytical challenges as outlined by the PMC, stepped-wedge designs should be avoided when another rigorous study design is feasible and will answer the study question. If proposed, a strong justification for a stepped-wedge design should be provided, including why an alternative design is not superior.

For projects proposing implementation science aims:

Outcomes of implementation trials should focus on rigorous assessment of the strategies designed to increase uptake and adoption of evidence-based nonopioid pain interventions. Investigators are encouraged to incorporate theories, models, and/or frameworks appropriate for implementation research when considering study hypotheses, measures, and outcomes. When designing an application, applicants are also encouraged to use the extant literature on barriers to and facilitators of the implementation of practices to manage pain and to consider the multilevel context and environment in which the proposed research will be conducted. 

Research Planning Phase and Research Execution Phase

These projects will be funded as phased awards with a 1-year research planning phase (UG3) and a 2–4-year research execution phase (UH3). The UH3 budget will undergo reassessment during the UG3 planning phase. Activities in both phases will depend on the specific study (e.g., type of intervention, randomization strategy, and proposed outcome measures).

During the UG3 or research planning phase, activities should generally include, but are not limited to:

• Identify project staff who will participate in work groups of the PMC (see Additional Information below), which will develop and update policies and practices to be implemented across PMC projects.
• Work with the PMC to comply with approved policies and practices for electronic data access extraction and sharing and develop quality control methods and tools. This could include developing and validating all electronic data methods and tools within the HCS needed for the demonstration project (e.g., EHRs, electronic methods for patient identification and outcomes assessment, biospecimens, images, genomic data, family history, and data abstraction, and survey instruments) and complete quality control testing at all sites.
• Assess adequacy and finalize clinically relevant outcome measures, which may include adding measures that are common across demonstration projects.
• Identify additional implementation sites, if needed, in consultation with NIH, the DOD, the VA, and the PMC3.
• Review analytic plans and power calculations with the biostatistics/design workgroup to optimize design and methods.
• Develop detailed plans for site implementation, including determining need and role of site staff; method of participant identification, recruitment, and acquisition; randomization (as applicable); and administration/implementation of the intervention, if applicable.
• Address all ethical, human subject safety, and oversight issues for the demonstration project, including development of informed consent documents or opt-out consent, if applicable, and finalizing single institutional review board (IRB) review for trial oversight, in accordance with the Revised Common Rule, and other requirements needed for implementing a study in a Veteran or military facility.
• Address all potential regulatory elements of the proposed trial (if applicable).
• Develop a detailed budget for conducting and completing the demonstration project, including preparation of a final study report.
• Develop detailed plans for data coordination and quality control, as these activities will not be provided by the PMC3.

The objective of the 2–4-year UH3 research execution phase is to conduct the effectiveness and/or implementation research within the PMC, in accordance with activities planned in the UG3 planning phase. UH3 activities will depend upon the study, but in general the following goals should be achieved:

• Each demonstration project is expected to implement all aspects of the proposed trial as finalized during the UG3 research planning phase.
• Each project is expected to provide a 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 to provide detailed and definitive testing of the validity of methods used for monitoring fidelity and outcome assessment.
• Each project is to provide all data coordination, cleaning, and analysis during the implementation of the trial.
• Each project is expected to provide periodic reports to a Data and Safety Monitoring Board, which may require closed reports including unmasked data prepared by an independent statistician.

Research Questions

Applicants who propose effectiveness aims should address one or more critical research questions to improve pain management for U.S. Veterans and military personnel. The following list provides examples of some potential research that addresses the effectiveness of evidence-based approaches delivered in the VA and DOD health care settings:

• Evaluation of evidence-based, nonopioid pain management/prevention approaches that also address common co-occurring conditions in Veterans and service members such as PTSD, TBI, and suicidal thoughts or behaviors
• Evaluation of evidence-based, integrative interventions that improve pain and comorbidity outcomes in populations that experience health inequities, such as individuals who are socioeconomically disadvantaged, from medically underserved rural areas, and/or from racial and ethnic minority groups and/or sexual and gender minority groups who receive care in the VA and DOD HCS
• Studies focusing on testing the timing, optimum components, and overall benefit of an individualized integrated package of nonopioid interventions such as mind-body therapies and other complementary health approaches
• Evaluation of team-based, coordinated health care versus provider-driven models of health care delivery particularly in settings in which military personnel or Veterans normally receive care
• Assessing approaches to address chronic overlapping pain conditions (COPCs), a set of painful chronic conditions with a high degree of co-occurrence and thought to have shared etiology) alone or while also addressing conditions comorbid with COPC in women Veterans and service members
• Evaluation of nonopioid pain management/prevention strategies for Veterans and service members with current opioid use/misuse
• Evaluating tailored approaches to address chronic pain in women Veterans who have experienced military sexual trauma
• Evaluating nonopioid pain management/prevention for chronic pelvic pain in women Veterans
• Studies to determine overall effectiveness of team-based care compared to conventional, non-team-based, primary care.
• Studies that include secondary outcomes to assess differential health benefits contributed by unique components of a team-based care package and the cost-effectiveness of the care package as a whole and of each component within the package compared to each other.
• Studies to identify mediators and/or moderators of positive outcomes associated with team-based care compared to conventional, non-team-based primary care (e.g., more efficient delivery of services, improved physician-patient communication and relationships, better treatment adherence, higher patient satisfaction).
• Assessment of the effectiveness of complementary and integrative pain management strategies to facilitate health restoration
• Assessment of integrative pain management approaches and strategies to be implemented in outpatient transitions of care from the DOD to the VA

Applicants who propose implementation science should address one or more critical research questions for implementing evidence-based pain management interventions for U.S. military personnel and Veterans. The following list provides examples of some of the potential research questions that might be addressed by such trials:

• Studies to test the effect of system-level innovations to improve implementation of established guidelines for nonopioid approaches to management of pain and comorbid conditions
• Studies of the implementation of multiple evidence-based pain management practices within community or clinical settings to meet the needs of Veterans and U.S. military personnel in  systems of care that serve Veterans and service members
• Studies of the local adaptation of evidence-based practices in the context of implementation
• Studies testing the effectiveness and cost-effectiveness of dissemination or implementation strategies for pain management to reduce health disparities and improve quality of care among rural, minority, low literacy and numeracy, and other underserved populations
• Studies on reducing or stopping (“de-implementing”) the use of clinical and community pain management practices that are ineffective, unproven, low value, or harmful
• Studies of influences on the creation, packaging, transmission, and reception of evidence-based nonopioid pain management interventions
• Studies that identify and test theories, models, and frameworks for dissemination and implementation (D&I) processes will be of higher programmatic priority.  
   

Milestones and UG3/UH3 Transition

Projects should include well-defined milestones for the research planning phase (UG3) and annual milestones for the research execution 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 program director/principal investigator (PD/PI) and NIH staff will negotiate a final list of milestones for each year of support prior to releasing an award.

Prior to the completion of the UG3 research planning phase, the applicant will be required to submit a detailed transition request for the UH3 demonstration project research execution phase at least 60 days before the anticipated transition date. UH3 transition requests will undergo an administrative review by the respective funding agency to determine whether the demonstration project will be awarded the research execution phase (UH3). Prospective applicants should note that initial funding of the UG3/UH3 cooperative agreement does not guarantee support of the UH3 demonstration project research execution phase. Successful completion of all UG3 milestones also does not guarantee transition to nor full support of the UH3 phase. Applicants should understand that transition to the UH3 phase of the project will occur only if an administrative review process concludes that the UG3 planning milestones have been successfully met and that the UH3 phase can proceed with confidence of success, continued relevance to the funding agency, and availability of funds.

Additional Information

Diversity

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 homogeneous 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. In spite of tremendous advancements in scientific research, information and, educational and research opportunities are not equally available to all. NIH encourages institutions to diversify their student and faculty populations to enhance the participation of individuals from groups that are underrepresented in the biomedical, clinical, behavioral, and social sciences. Please refer to Notice of NIH’'s Interest in Diversity NOT-OD-20-031 for more details.

Engaging People with Lived Experience and Other Collaborators:

People with lived experience (e.g., patients, patient advocates, caregivers, families, community leaders) have important insights that can improve meaningful outcomes, uptake of research findings, and health equity across the continuum of research from basic through implementation studies. The perspectives of other relevant collaborators (e.g., health service providers, payors, public health agencies, community-based organizations, biotech, pharma) can further improve research impact. The NIH HEAL initiative strongly encourages applicants to specify their plan for meaningful engagement of people with lived experience and other collaborators in the research process. Meaningful engagement will vary with the focus of the research but should at minimum ensure that researchers are connecting with relevant collaborators and incorporating their perspectives throughout the conception, implementation, and dissemination of the research. Meaningful engagement should address what the researchers will learn and how the people with lived experience and/or collaborators will benefit from the partnership. To promote health equity, as is relevant for the research proposed, it is recommended that at least two people with lived experience from populations who experience health disparities should be meaningfully engaged in these efforts (see NIH’s Notice of Interest in Diversity for more information: NOT-OD-20-031).

See this resource for more information in engaging people with lived experience: https://aspe.hhs.gov/lived-experience).

Governance: The awards funded under this NOFO will be cooperative agreements (see Section VI.2 Cooperative Agreement Terms and Conditions of Award).

Participation in the work groups established by the PMC3 is a 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 are vetted in these groups. Work groups include Stakeholder Engagement, Patient Resources, Ethical/Regulatory, Design/Biostatistics, Phenotype/Outcomes, Electronic Health Records, Implementation Science, and Data Sharing. Work groups comprise individuals from the demonstration projects, the PMC3, and staff from NIH, the DOD, and the VA.

The PMC3 has established a steering committee to address issues that span all projects, provide input into the policies and processes of the PMC, and assist in dissemination of policies and processes that enable research in HCS serving the military and Veterans, involving their patients and practitioners. The steering committee includes at a minimum, one representative from each of the demonstration projects, one representative from each work group, one representative from the PMC3, program officers and project scientists from NIH and representatives from various NIH institutes and centers (ICs). All members are expected to actively participate in all steering committee activities.

Types of Research Not Responsive to This NOFO

The following types of research are not responsive to this NOFO, and applications proposing such activities will be deemed nonresponsive and will not be reviewed:

• Applications that do not include effectiveness research, and implementation trials, and/or hybrid effectiveness-implementation trials
• Applications that only propose dissemination research
• Phase I (first-in-human) trials whether single site or multisite
• Single site trials

Special Considerations:

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. Additionally, applications must budget for project PD(s)/PI(s) travel to attend an annual one-and-a-half-day PMC steering committee meeting in the greater Washington D.C. area.

Clinical Trial Accrual:

This NOFO will support applications that include a series of recruitment milestones for completion of the clinical trial and provide contingency plans to proactively confront potential delays or disturbances in attaining the milestones. Continuation of the award is conditional upon satisfactory progress, availability of funds, and scientific priorities of the HEAL Initiative. If, at any time, recruitment falls significantly below the projected milestones for recruitment, NIH will consider ending support and negotiating an orderly phase-out of the award. NIH retains the option of periodic external peer review of progress. NIH program staff will closely monitor progress at all stages for milestones, accrual, and safety.

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

Plan for Enhancing Diverse Perspectives (PEDP)

The NIH recognizes that teams comprised of investigators with diverse perspectives working together and capitalizing on innovative ideas and distinct viewpoints outperform homogeneous teams. There are many benefits that flow from a scientific workforce rich with diverse perspectives, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved populations participate in, and benefit from research, and enhancing public trust.

To support the best science, the NIH encourages inclusivity in research guided by the consideration of diverse perspectives. Broadly, diverse perspectives can include but are not limited to the educational background and scientific expertise of the people who perform the research; the populations who participate as human subjects in research studies; and the places where research is done.

This NOFO requires a Plan for Enhancing Diverse Perspectives (PEDP), which will be assessed as part of the scientific and technical peer review evaluation.  Assessment of applications containing a PEDP are based on the scientific and technical merit of the proposed project. Consistent with federal law, the race, ethnicity, or sex (including gender identify, sexual orientation, or transgender status) of a researcher, award participant, or trainee will not be considered during the application review process or when making funding decisions.  Applications that fail to include a PEDP will be considered incomplete and will be administratively withdrawn before review.

The PEDP will be submitted as Other Project Information as an attachment (see Section IV).  Applicants are strongly encouraged to read the NOFO instructions carefully and view the available PEDP guidance materials.

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 NOFO.

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 Organizations) 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 How to Apply - 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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information

• 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 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 their organization to develop an application for support. Individuals from diverse backgrounds, including individuals from 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 How to Apply - Application Guide.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement NIH Grants Policy Statement Section 1.2 Definition of Terms.

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 NIH Grants Policy Statement Section 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 NIH Grants Policy Statement 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 NOFO. 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 How to Apply - Application Guide nbsp;except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the How to Apply - 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:

Jessica McKlveen, Ph.D.
Telephone: 301-594-8018
Email: [email protected] 

Page Limitations

All page limitations described in the How to Apply – Application Guide and the Table of Page Limits must be followed.

, with the following exceptions or additional requirements; 

For this specific NOFO, the Research Strategy section is limited to 30 pages.

The following section supplements the instructions found in the How to Apply – Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the How to Apply - Application Guide must be followed.

Plan for Enhancing Diverse Perspectives (PEDP)

• In an "Other Attachment" entitled "Plan for Enhancing Diverse Perspectives," all applicants must include a summary of actionable strategies to advance the scientific and technical merit of the proposed project through expanded inclusivity.
• Applicants should align their proposed strategies for PEDP with the research strategy section, providing a holistic and integrated view of how enhancing diverse perspectives and inclusivity are buoyed throughout the application.
• The PEDP will vary depending on the scientific aims, expertise required, the environment and performance site(s), as well as how the project aims are structured.
• The PEDP may be no more than 2 pages in length and should include:
  • Actionable strategies using defined approaches for the inclusion of diverse perspectives in the project;
  • Description of how the PEDP will advance the scientific and technical merit of the proposed project;
  • Anticipated timeline of proposed PEDP activities;
  • Evaluation methods for assessing the progress and success of PEDP activities.

Examples of items that advance inclusivity in research and may be appropriate for a PEDP can include, but are not limited to:

• Partnerships with different types of institutions and organizations (e.g., research-intensive; undergraduate-focused; HBCUs; emerging research institutions; community-based organizations).
• Project frameworks that enable communities and researchers to work collaboratively as equal partners in all phases of the research process.
• Outreach and planned engagement activities to enhance recruitment of individuals from diverse groups as human subjects in clinical trials, including those from underrepresented backgrounds.
• Description of planned partnerships that may enhance geographic and regional diversity.
• Outreach and recruiting activities intended to diversify the pool of applicants for research training programs, such as outreach to prospective applicants from groups underrepresented in the biomedical sciences, for example, individuals from underrepresented racial and ethnic groups, those with disabilities, those from disadvantaged backgrounds, and women.
• Plans to utilize the project infrastructure (i.e., research and structure) to enhance the research environment and support career-advancing opportunities for junior, early- and mid-career researchers.
• Transdisciplinary research projects and collaborations among researchers from fields beyond the biological sciences, such as physics, engineering, mathematics, computational biology, computer and data sciences, as well as bioethics.

Examples of items that are not appropriate in a PEDP include, but are not limited to:

• Selection or hiring of personnel for a research team based on their race, ethnicity, or sex (including gender identify, sexual orientation, or transgender status).
• A training or mentorship program limited to certain researchers based on their race, ethnicity, or sex (including gender identify, sexual orientation, or transgender status).

For further information on the Plan for Enhancing Diverse Perspectives (PEDP), please see PEDP guidance materials.

SF424(R&R) Senior/Key Person Profile

All instructions in the How to Apply - Application Guide must be followed.

Biosketches should reflect the PD(s)/PI(s) and key personnel’s expertise in design and conduct of large-scale clinical and/or implementation trials within U.S. military and Veteran health care delivery organizations. The experience of the investigative team with successful recruitment and retention of participants should be described.

R&R Budget

All instructions in the How to Apply - Application Guide must be followed.

Budgets for both phases (UG3/UH3) should 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 percent annually (2.4 person months) to the project. If a project includes multiple PDs/PIs, the total annual PD/PI effort must be at least 2.4 person months. There must be an appropriate mix of time allocated for more established and early career stage scientists to ensure the successful conduct of the study. Budgeted effort of other personnel must be appropriate to the needs of the project. The budget must include personnel at all participating DOD and VA 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 the work groups.

Applications must budget for project PD(s)/PI(s) travel to attend an annual one-and-a-half-day PMC steering committee meeting in the greater Washington, D.C. area.

PEDP implementation costs:

Applicants may include allowable costs associated with PEDP implementation (as outlined in the Grants Policy Statement section 7): https://grants.nih.gov/grants/policy/nihgps/html5/section_7/7.1_general.htm.

R&R Subaward Budget

All instructions in the How to Apply - Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the How to Apply - Application Guide must be followed.

PHS 398 Research Plan

All instructions in the How to Apply - 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., disease domains, type of interventions, experimental design, randomization strategy, and proposed outcome measures).

In preparing the application, investigators should consider 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. Within the designated page limit, include separate aims for both the UG3 and UH3 phases, and clearly label them as UG3 specific aims and UH3 specific aims.

Research Strategy: Description of the demonstration project should provide background on the underlying health question and the evidence supporting the potential of the tested intervention(s) to improve management of pain and, if applicable, other co-occurring conditions.

It is not necessary to repeat background information or details of methods in the UH3 portion that were provided in the UG3 portion. 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.

Applications should describe the significance of the proposed demonstration project to improve and/or implement nonopioid approaches for the management of pain and comorbidities in U.S. Veterans and military personnel. Innovative strategies to impact current conventional approaches to trials utilizing novel approaches or methodologies for a pragmatic or implementation trial that will increase uptake of the approach in a DOD/VA environment should be described.

Applications should describe the expertise of the interdisciplinary teams as a whole, including military researchers on military-focused applications and VA researchers on Veteran-focused applications. Study team should also include expertise in the design and conduct of large-scale pragmatic trials and/or implementation science within an HCS network serving military personnel, Veterans, and their families (including using EHRs for recruitment and outcomes assessment). Do not repeat information described in individual biosketches.

For applications proposing effectiveness aims, the application must include a thorough description of the proposed trial including appropriate controls with broad but adequate eligibility criteria. For applications proposing implementation aims, the application must include a thorough description of the implementation strategies to be tested. Investigators should include any plans to adapt implementation strategies during the study.

In the Research Strategy, both the UG3 research planning phase and the UH3 research execution phase must each have a section of proposed milestones provided in a separate subheading at the end of the specificci UG3 and UH3 portions. Milestones should be well described, feasible, quantifiable, and scientifically justified to allow an assessment of progress. For UG3 milestones, applicants should delineate what they aim to achieve to justify proceeding to the UH3 phase. The UG3 milestones should 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. Proposed annual milestones for the UH3 phase should be included, although it is understood that timelines and milestones included in the application will likely evolve as activities in the UG3 phase progress.

Applicants must indicate their willingness to participate in PMC work groups and comply with policies and practices developed by the work groups, and to work with the PMC3 in providing relevant information and material.

To increase the yield of the programs and improve comparisons between studies, as well as facilitate data sharing, multiple ICs encourage the use of CDEs. A plan to incorporate CDEs, where appropriate, should be included in the Approach.

Letters of Support: Applications must include letters of support from the HCS partners that relate their commitment to the proposed research and outline how the project fits with organizational priorities. The letters of support must address the quality of the proposed EHR and data systems and the commitment of their IT staff to the project including commitment/support during any transition in EHR platform. The letters must provide a description of how the project would directly impact delivery of health care within their organizations. The letters must also relate a willingness to adopt and implement the proposed Resource Sharing and Data Management and Sharing Plans.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide.

Other Plan(s): 

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

PMC Resources and Data Sharing 

The PMC encourages sharing of data, resources, policies, best practices, materials, and tools to facilitate collaboration, use, and replication of results. The PMC demonstration projects will work with the PMC3 in the following areas:

• Development of best practices for data sharing across the PMC and in agreement with NIH data management and sharing policy 
• Consultations related to the project Data Management and Sharing Plan implementation 
• Promoting the use of NIH HEAL Initiative CDEs across demonstration projects. 
• Harmonizing, as appropriate, data elements to create opportunities for combined datasets across projects for cross-project analyses.

All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

The HEAL Initiative has additional requirements that must be addressed in the Data Management and Sharing plan. All HEAL-generated data must be shared through the HEAL Initiative Data Ecosystem following HEAL’s compliance guidance (https://heal.nih.gov/data/complying-heal-data-sharing-policy). Specifically, HEAL applicants must include:

• Plans to submit data and metadata (and code, if applicable) to a HEAL-Compliant data repository (https://www.healdatafair.org/resources/guidance/selection) and follow requirements of the selected repository.
• Plans to register your study with the HEAL platform within one year of award (https://heal.github.io/platform-documentation/study-registration/).
• Plans to submit HEAL-defined study-level metadata within one year of award (https://github.com/HEAL/heal-metadata-schemas/blob/main/for-investigators-how-to/study-level-metadata-fields/study-metadata-schema-for-humans.pdf) and https://heal.github.io/platform-documentation/slmd_submission/).
• Plans to submit data dictionaries to the HEAL Data Ecosystem, if applicable.
• HEAL pain clinical studies must include plan to use HEAL core Common Data Elements (https://heal.nih.gov/data/common-data-elements). 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.
• To the extent possible, all other (non-pain) HEAL studies conducting clinical trials or research involving human subjects are expected to use questionnaires by the HEAL Clinical Data Elements (CDE) Program (https://heal.nih.gov/data/common-data-elements) if applicable and relevant to their research.
• Studies using CDEs, regardless of whether they are part of the HEAL repository, will be required to report which questionnaires are being used.
• To the extent possible, HEAL awardees are expected to integrate broad data sharing consent language into their informed consent forms.

HEAL has developed additional details and resources to fulfill these requirements (https://www.healdatafair.org/resources/road-map). Budgeting guidance for data sharing can be found in NOT-OD-21-015 and the NIH Scientific Data Sharing site.

HEAL Public Access and Data Sharing Policy:

NIH intends to maximize the impact of HEAL Initiative-supported projects through broad and rapid data sharing and immediate access to publications (https://heal.nih.gov/about/public-access-data). Guidelines for complying with the HEAL Public Access and Data Sharing Policy can be found at https://heal.nih.gov/data/complying-heal-data-sharing-policy.  Resources and tools to assist with data related activities can be found at https://www.healdatafair.org/. For more detail and specific data sharing requirements, see Section 4. Other plans.

Publications resulting from NIH HEAL Initiative funded studies must be immediately publicly available upon publication.

• For manuscripts published in journals that are not immediately open access, authors should arrange with journals in advance to pay for immediate open access.
• Costs to ensure manuscripts are immediately publicly available upon publication should be included in budget requests. 

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply - 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 How to Apply - 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 How to Apply - Application Guide must be followed.

Section 2 - Study Population Characteristics

2.5 Recruitment and Retention Plan

Describe the following: 1) recruitment milestones; 2) 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; 3) 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; 4) contingency plans for participant accrual if enrollment significantly lags behind accrual benchmarks; 5) participant retention and adherence strategies; and 6) possible competition from other trials for study participants.

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 recruitment milestones and key project management activities. A narrative is not expected in this section.

The study timeline should include core criteria and milestones that need to be met throughout the life cycle 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 the study opens to enrollment
(b) When recruitment milestones (see below) are met
(c) What subtasks are needed to reach of the recruitment 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 

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 How to Apply - Application Guide must be followed.

PHS Assignment Request Form

All instructions in the How to Apply - Application Guide must be followed.

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

See Part 2. 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. 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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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 How to Apply – 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 Section 7.9.1 Selected Items of Cost.

Applications must be submitted electronically following the instructions described in the How to Apply - 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 NOFO 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 How to Apply - Application Guide.

See more tips for avoiding common errors.

Applications must include a PEDP submitted as Other Project Information as an attachment. Applications that fail to include a PEDP will be considered incomplete and will be administratively withdrawn before review.

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, noncompliant, and/or nonresponsive will not be reviewed.

In order to expedite review, applicants are requested to notify the NCCIH Referral Office by email at [email protected] when the application has been submitted. Please include the NOFO number and title, PD/PI name, and title of the application.

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at [email protected]. 

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy

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 particular NOFO, note the following:

This NOFO supports demonstration projects that are feasible and impactful in nature and will significantly move the overall program forward.

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).As part of the overall impact score, reviewers should consider and indicate how the Plan to Enhance Diverse Perspectives affects the scientific merit of the project.

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 policies and practices, 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 NOFO.

Applications will be assigned  to the NCCIH. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. 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 , including the PEDP, as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

Please note that reviewers will not consider race, ethnicity, age, or sex (including gender identity, sexual orientation or transgender status) of a researcher, award participant, or trainee, even in part, in providing critiques, scores, or funding recommendations. NIH will not consider such factors in making its funding decisions.

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 Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant’s federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov.  NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant’s integrity, business ethics, and performance record of managing Federal awards per 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.

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 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient’s business official.

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.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk.  For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.

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

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. 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.
• If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by the HHS Office for Civil Rights website. 
  • HHS recognizes that NIH 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 NOFO.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations.  NIH may terminate awards under certain circumstances.  See 2 CFR Part 200.340 Termination and NIH Grants Policy Statement Section 8.5.2 Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding of Support. 

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 (HHS) grant administration regulations at 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 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 NIH as defined below.

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

• The PD(s)/PI(s) are responsible for overseeing the overall budget, activities, and performance of the demonstration project.
• The PD(s)/PI(s) is (are) expected to participate in all meetings of the PMC steering committee as voting members. The PD(s)/PI(s) compile(s) for the steering committee and NIH program directors regular reports of accomplishments and roadblocks, as well as conference and meeting summaries, coordinating center performance reports, and other reports as needed and requested.
• In addition, the PD(s)/PI(s) will identify study team members with relevant expertise who will participate in program-wide work groups and subcommittees.
• The PD(s)/PI(s) is (are) expected to cooperate with the PMC steering committee, research partners, and NIH staff in the design and conduct of protocols, analysis of data, and reporting of results of research undertaken by the PMC3 on behalf of the program.
• The PD(s)/PI(s) will agree to accept the participatory and cooperative nature of the collaborative research process, will comply with policies and practices developed by the PMC work groups, and work with the PMC3 in providing relevant information and materials.
• Recipients will support additional subcommittees, task forces, and advisory panels as needed.
• Any of the above functions may be performed by the applicant organization or by subcontract to the applicant organization.
• The PD(s)/PI(s) will share data, resources, and software according to the approved sharing policies for the PMC3 program and consistent with NIH sharing policies.
• The PD(s)/PI(s) agree to accept close coordination, cooperation, and management of the project with NIH and PMC program funding partners (the DOD and the VA), including those outlined under “NIH Programmatic Involvement.”
• The PD(s)/PI(s) will submit periodic progress reports, including materials for the In Progress Review (IPR) in a standard format, as agreed upon by the steering committee and NIH.
• Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies and achieving the goals of this program.
• Recipient(s) agree to the governance through a steering committee. A PMC program steering committee has been established to address issues that span all projects, provide input into the policies and processes of the PMC, and assist in dissemination of policies and processes that enable research in partnership with HCS, their patients, and practitioners.
• The PD(s)/PI(s) will provide updates at least annually on PEDP implementation.

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

• The NIH program official and project scientists 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 scientists.
• Additional NIH, DOD, and VA staff may participate in all work groups, implementation teams, and committees, including the steering committee, as appropriate. Participation by staff from other Federal agencies may also be appropriate and advantageous to facilitate the activities of the program.
• 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.
• NIH, DOD, and VA staff will act as a resource and facilitator for activities of the recipient with non-HCS researchers and other NIH, DOD, VA, DHHS, or other federally sponsored research networks that may be relevant to this effort.
• NIH, DOD, and VA staff will provide input, expert advice, and suggestions in the design, development, and coordination of the infrastructure development and implementation efforts, and the domain development and research projects.
• 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 their 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 matters.
• An NIH program official or NIH program director will be responsible for the normal programmatic stewardship of the award and will be named in the award notice. Additionally, an NIH project scientist will be responsible for the scientific stewardship of the cooperative agreement award and will be named in the award notice.

Areas of joint responsibility include:

• The PD(s)/PI(s) provide, in concert with the NIH staff, support necessary to ensure that HCS sites and investigators, and NIH, DOD, VA, and other research partners fully comply with Federal regulatory requirements, including but not limited to those relating to human subjects protections, informed consent, and reporting of adverse events.
• Recipients and NIH, the DOD, and the VA will jointly develop 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 PMC research projects.
• The PD(s)/PI(s) agree(s) to the governance through a steering committee. A PMC steering committee has been established to address issues that span all projects, provide input into the policies and processes of the PMC, and assist in dissemination of policies and processes that enable research in partnership with HCS, their patients, and practitioners that provide care for military personnel, Veterans, and their families. The steering committee includes at a minimum, one representative from each of the demonstration projects; one representative from each work group; one representative from the PMC3; program officers and project scientists from PMC projects funded by NIH, the DOD, and the VA, and representatives from various NIH ICs, the DOD, and the VA. All members are expected to actively participate in all steering committee activities. The combined vote of NIH, DOD, and VA programmatic members may never exceed 40 percent of the total. Program officials will serve as nonvoting members of the steering committee. Each project scientist will have a vote. In the event that any of the Federal agencies involved (NIH, the DOD, and the VA) have more than one project scientist serving on the steering committee, the project scientists will have a collective vote representing each agency.
• Participation in the PMC work groups is a 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 are vetted in these groups. Work groups include: Stakeholder Engagement, Ethical/Regulatory, Study Design/Biostatistics, Phenotype/Outcomes, Electronic Health Records, Implementation Science, and Data Sharing. Work groups are chaired by PMC3 staff and open to participation by individuals from all funded demonstration projects, the PMC3, and the NIH, the DOD, and the VA.
• Demonstration project recipients will work with the PMC3 and NIH, the DOD, and the VA through all phases of their projects, including the research execution and closeout phases, to assure all resources, materials, protocols, data, best practices, and lessons learned, as well as software or sets of code, are disseminated broadly through the PMC3 with all PMC program resources.
• All recipients and NIH, the DOD, and the VA will cooperate to ensure the timely and broad dissemination of all PMC program endorsed policies and practices and lessons learned in the program, to inform researchers and HCS 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 NIH may be brought to dispute resolution. A dispute resolution panel composed of three members will be convened. The three members will be 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 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. Data Management and Sharing

Consistent with the 2023 NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

HEAL Data Sharing Requirements

NIH intends to maximize the impact of HEAL Initiative-supported projects through broad and rapid data sharing.  All HEAL Initiative award recipients, regardless of the amount of direct costs requested for any one year, are required to comply with the HEAL Public Access and Data Sharing Policy. HEAL award recipients must following all requirements and timelines developed through the HEAL Initiative Data Ecosystem (https://heal.nih.gov/about/heal-data-ecosystem), as described in HEAL’s compliance guidance (See “Already Funded” section: https://heal.nih.gov/data/complying-heal-data-sharing-policy): 
 

1. Select a HEAL – Compliant data repository (https://www.healdatafair.org/resources/guidance/selection)

• Data generated by HEAL Initiative-funded projects must be submitted to study-appropriate, HEAL-compliant, data repositories to ensure the data is accessible via the HEAL Initiative Data Ecosystem.
• Some repositories require use of specific data dictionaries or structured data elements, so knowing your repository’s requirements up front can help reduce the burden of preparing data for submission.
• HEAL-funded awardees must follow requirements for selected repository

2. Within one year of award, register your study with the HEAL platform (https://heal.github.io/platform-documentation/study-registration/)

• This process will connect the Platform to information about your study and data, including metadata, and identify the selected repository. HEAL requests initial submission within one year of award, with annual updates, and to be updated in accordance with any release of study data.

3. Within one year of award, submit HEAL-specific study-level metadata.

• Some of the required study-level metadata (https://github.com/HEAL/heal-metadata-schemas/blob/main/for-investigators-how-to/study-level-metadata-fields/study-metadata-schema-for-humans.pdf) will be auto-populated as part of the registration process.
   

4. Submit data and metadata (and code, if applicable) to HEAL-Compliant repository

• At the completion of the study and/or when prepared to make the final data deposits in the repositor(ies) of choice, ensure your study registration (https://heal.github.io/platform-documentation/study-registration/) is complete.
• Submit data dictionaries to the HEAL data ecosystem, if applicable.
• The NIH HEAL Initiative expects data sharing timelines to align with timeline requirements stated in the Final NIH Policy for Data Management and Sharing (NOT-OD-21-013).

6. Additional Requirements for HEAL Initiative studies conducting clinical research or research involving human subjects.

These studies must meet the following additional requirements:

• HEAL Initiative trials that are required to register in clinicaltrials.gov should reference support from and inclusion in the HEAL Initiative by including the standardized terms “the HEAL Initiative (https://heal.nih.gov/)” in the Study Description Section.
• All new HEAL clinical pain studies are required to use core questionnaires required by the HEAL Clinical Data Elements (CDE) Program (https://heal.nih.gov/data/common-data-elements). Outside of the core questionnaires, studies should select questionnaires from among the repository of supplemental questionnaires that are already being used by other HEAL clinical pain studies. The program has created the CDE files containing standardized variable names, responses, coding, and other information for all of these questionnaires The program has also formatted 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); https://www.govinfo.gov/content/pkg/USCODE-2011-title29/html/USCODE-2011-title29-chap16-subchapV-sec794d.htm) which “require[s] Federal agencies to make their electronic and information technology accessible to people with disabilities.”
  • Studies that wish to use questionnaires not already included in the HEAL CDE repository should consult with their program official and the HEAL CDE team. New questionnaires will be considered for inclusion in the repository on a case-by-case basis and only when appropriate justification is provided.
  • 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 (https://heal.nih.gov/data/common-data-elements).
• To the extent possible, all other (non-pain) HEAL studies conducting clinical trials or research involving human subject are expected to use questionnaires by the HEAL Clinical Data Elements (CDE) Program (https://heal.nih.gov/data/common-data-elements) if applicable and relevant to their research.
• To the extent possible, HEAL awardees are expected to integrate broad data sharing consent language into their informed consent forms.

Additional details, resources, and tools to assist with data related activities can be found at https://www.healdatafair.org/. Budgeting guidance for data sharing can be found in NOT-OD-21-015 and the NIH Scientific Data Sharing site.

All data collected as part of the NIH HEAL Initiative are so collected under a Certificate of Confidentiality and entitled to the protections thereof. Institutions who receive Data and/or Materials from this award for performance of activities under this award are required to use the Data and/or Materials only as outlined by the NIH HEAL Initiative, in a manner that is consistent with applicable state and federal laws and regulations, including any informed consent requirements and the terms of the institution’s NIH funding, including NOT-OD-17-109 and 42 U.S.C. 241(d). Failure to adhere to this criterion may result in enforcement actions.

4. 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 Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

• Recipients will provide updates at least annually on implementation of the PEDP.

Publications resulting from NIH HEAL Initiative funded studies must be immediately publicly available upon publication. 

• For manuscripts published in journals that are not immediately open access, authors should arrange with journals in advance to pay for immediate open access 
• Costs to ensure manuscripts are immediately publicly available upon publication should be included in budget requests  

  Prior to publication, HEAL expects investigators to alert their program officers of upcoming manuscripts to ensure coordination of communication and outreach efforts. 

  Award recipients and their collaborators are required to acknowledge HEAL Initiative support by referencing in the acknowledgment sections of any relevant publication:

  “This research was supported by the National Institutes of Health through the NIH HEAL Initiative (https://heal.nih.gov/) under award number [include specific grant/contract/award number; with NIH grant number(s) in this format: R01GM987654].” 

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 Section 8.6 Closeout. NIH NOFOs 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 2 CFR Part 200.301.

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: https://www.era.nih.gov/need-help (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]

Peter Murray, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-496-4054
Email: [email protected] 

Mark Egli, Ph.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Phone: 301-594-6382
E-mail: [email protected]

David Frankowski, Ph.D.
National Institute on Aging (NIA)
E-mail: [email protected]

Jessica McKlveen, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-594-8018
Email: [email protected] 

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

Judy Fox
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-4704
Email: [email protected]

Kathleen Moy
National Institute on Aging (NIA)
Phone: 301.827.2856
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 2 CFR Part 200.