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

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

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Background

Since 2001, more than 2.77 million U.S. troops have been deployed for Operation New Dawn, Operations Enduring Freedom (OEF) in Afghanistan and Iraqi Freedom (OIF) in Iraq. The all-volunteer military experienced multiple redeployments to the war zone, 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% of active-duty service members and 50% of V eterans experience pain on a regular basis and there is significant overlap between 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 nonpharmacologic approaches to complement or replace pharmacological 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 on "Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research" (http://iom.edu/Reports/2011/Relieving-Pain-in-America-A-Blueprint-for-Transforming-Prevention-Care-Education-Research.aspx). 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, U.S. Department of Defense (DoD), and 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 VA to fund 13 grants to research military and Veteran health with a focus on nonpharmacologic approaches to pain and related conditions. This important partnership was expanded in 2017 to include the DoD and additional NIH agencies (NINDS, NIAAA, NICHD, ORWH, OBSSR, and NINR) to initiate the NIH-DoD-VA Pain Management Collaboratory (PMC). The first wave of the Pain Management Collaboratory resulted in the support of 11 research projects focused on the development and testing of nonpharmacologic approaches to pain management (RFA-AT-17-001) as well as a Coordinating Center (RFA-AT-17-002). A twelfth research project was funded in FY22 (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 targeted organizations 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 service members.

Team-based care is increasingly recognized as fundamental to effective health care systems. Defined as the 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 cut down significantly on health care costs, estimating savings of $240 billion annually in national health care expenditures.

Despite the recognized and compelling need for research to identify and implement effective complementary nonpharmacologic approaches for pain management 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, research studies have frequently used endpoints that are not part of routine patient assessments of care and may support adoption of interventions that are challenging to implement in many health care delivery settings. Multiple challenges remain in identifying the best strategies to successfully integrate evidence-based interventions within specific health care settings. 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 even additional 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, and environment, the physical as well as social. Past models of pain management that focus mainly on physiological systems are incomplete and fall short of accessing the full capacity of human health and health restoration. Recognizing the importance of a multi-domain approach to health, the DoD, 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 is 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 encompassing 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 and treating, not just the pain, but also the comorbidities that so often occur with and exacerbate and are exacerbated by pain. It is also important to note the well-documented racial and ethnic disparities in both the experience and 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 trial and/or implementation science Demonstration Projects within the infrastructure of the NIH-DoD-VA Pain Management Collaboratory on nonpharmacologic approaches to pain management and other comorbid conditions in U.S. military personnel, Veterans and their families. The PMC 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.

This new wave of the NIH-DoD-VA Pain Management Collaboratory awards solicited under the NOFO will:

• 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 nonpharmacologic approaches to pain management 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 from these Demonstration Projects to facilitate a research partnership with health care delivery systems that provide care to Veterans, military personnel, and/or their families

Demonstration Projects funded through this NOFO will be expected to work collaboratively with the Pain Management Collaboratory Coordinating Center (PMC3) and the other PMC projects funded under the previous waves of PMC trials as well as those funded under this NOFO. This includes participation in PMC3 work groups, developing 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 potentially integrating common data elements to increase the overall impact of findings.

Awards made under this NOFO will initially support a one-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 nonpharmacologic approaches to pain management 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 utilize more pragmatic approaches rather than explanatory 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 non-responsive.

The research question(s) proposed should be of major public health importance focusing on nonpharmacologic approaches to pain management and comorbid conditions in Veterans, military personnel, and their families and one that will engage partnership with health care delivery systems providing services to this population. Although trials will 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. Types of nonpharmacologic approaches to study could include, but are not limited to, mindfulness/meditative interventions (e.g., mindfulness based stress reduction, meditation), movement based interventions (e.g., tai chi, yoga), manual therapies (e.g., spinal manipulation, massage, acupuncture), neuromodulation (e.g., electrical stimulation), and psychological and behavioral interventions (e.g., mindfulness-based cognitive behavioral therapy), or an integrative approach in which a complementary health approach is used in combination with standard care (e.g., cognitive behavioral therapy combined with standard pharmaceutical treatment). Of special interest are effectiveness trials of approaches which 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. 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 on-going 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, etc.) will be of higher programmatic priority.

It is anticipated that the Demonstration Projects will generally be performed within large health care systems that utilize electronic health records 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 HCSs 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. Demonstration Project applicants should include and involve appropriate personnel, from health care systems providing care to these populations, and be able to document the commitment of the health care organization to the project.

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 with functional changes.

When testing effectiveness, projects are encouraged to enroll participants based on broad eligibility criteria to maximize diversity, 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 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.

Effective prevention and treatment of mental illness have the potential to reduce morbidity and mortality associated with intentional injury (i.e., suicide attempts and deaths, see reports from the Veterans Administration, the Department of Defense, and the National Action Alliance for Suicide Prevention). Lack of attention to the assessment of these outcomes has limited our understanding regarding the degree to which effective mental health interventions might offer prophylaxis. Accordingly, where feasible and appropriate, this NOFO encourages the consideration of the NIMH recommendation that effectiveness research include assessment of suicidal behavior in order to advance understanding of how effective prevention and treatment of mental disorders might impact suicide relevant outcomes.

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 NIH Pragmatic Trials Collaboratory, 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 nonpharmacologic 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 utilize the extant literature on barriers to and facilitators of the implementation of practices to manage chronic pain and to consider the multi-level context and environment in which the proposed research will be conducted.

Specific Areas of Research Interest

National Institute of Nursing Research (NINR)

The National Institute of Nursing Research (NINR) supports research to solve pressing health challenges and inform practice and policy - optimizing health and advancing health equity into the future. NINR discovers solutions to health challenges through the lenses of health equity, social determinants of health, population and community health, prevention and health promotion, and systems and models of care. Drawing on the strengths of nursing’s holistic, contextualized perspective, core values, and broad reach, NINR funds multilevel and cross-sectoral research that examines the factors that impact health across the many settings in which nurses practice, including homes, schools, workplaces, clinics, justice settings, and the community. In the context of this NOFO, NINR's interests include, but are not limited to: 1. Studies that examine multi-disciplinary, multi-level interventions or intervention bundles that focus on a holistic, contextualized approach to pain. 2. Studies focused on social needs affecting pain in Veterans, military service members, and their families. 3. Studies that address the interaction between social determinants of health and the implementation and response to the intervention or intervention bundle. 4. Studies focused on advancing health equity and reducing disparities in rural, minority, low literacy, and other underserved populations, especially those that include engagement of members of the targeted population. 5. Studies that focus on nurse-led models of care that encompass the whole person, in the context of their lives and living conditions.

Research Planning Phase and Research Execution Phase

These projects will be funded as phased awards with a one-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 NIH-DoD-VA Pain Management Collaboratory (see Additional Information below), which will develop and update policies and practices to be implemented across PMC projects.
• Work with the NIH-DoD-VA Pain Management Collaboratory 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 HCSs needed for the Demonstration Project (e.g., Electronic Health Records (EHRs), electronic methods for patient identification and outcomes assessment, biospecimens, images, genomic data, family history, 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 the NIH, DoD, VA, and the Pain Management Collaboratory Coordinating Center.
• Review of analytic plans and power calculations with 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 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.
• Demonstration Project Research Execution Phase (UH3): The objective of the 2 4-year UH3 research execution phase is to conduct the effectiveness and/or implementation research within the NIH-DoD-VA Pain Management Collaboratory, 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 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, military personnel, and their families. The following list provides examples of some of the potential research questions that might be addressed by such pragmatic trials:

• Studies focusing on testing the timing, optimum components and overall benefit of an individualized integrated package of nonpharmacologic 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;
• Evaluation of sex and gender differences important for optimizing pain treatment;
• Evaluation of evidence-based, integrative interventions that improve pain and comorbidity outcomes in populations that experience health inequities, such as individuals that 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 health care systems;
• Assessment of the effectiveness of integrative pain management strategies to reduce the transition from acute to chronic pain, for example in the peri-operative period;
• Assessment of the effectiveness of integrative preventative strategies to prevent the development of chronic pain and/or the development of conditions that commonly co-occur with pain in high-risk individuals;
• Assessment of the effectiveness of complementary and integrative pain management strategies to facilitate health restoration, for example, post-operatively;
• Assessment of integrative pain management approaches and strategies to be implemented in outpatient transitions of care from DoD to VA;
• Studies evaluating the impact of behavioral approaches (e.g., motivational interviewing, meditation, mindfulness, yoga, tai chi, special diet) to conditions that are common co-morbidities with pain such as TBI, PTSD, sleep disturbance, and anxiety;
• Studies evaluating interventions comprised of multiple components (e.g., yoga plus mindfulness-based stress reduction)
• Studies to assess whether nonpharmacologic sleep treatments may improve both sleep and pain outcomes or studies to address whether treatment of sleep apnea results in improvements in chronic pain;
• Studies to test the value of technology-based tools for either self-monitoring or communication with providers; for example, studies could examine the value of a smart-phone application as an extension of a behavioral intervention for pain or test the value of technology-based collaborative interactions in a primary care environment.

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, Veterans, and their families. 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 nonpharmacologic approaches to pain management 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, U.S. military personnel and their families in diverse systems of care;
• 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 nonpharmacologic 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.

Applicants who propose to evaluate team-based care models should address one or more critical research questions regarding comparative effectiveness in managing pain among U.S. military personnel, Veterans, and their families. The following list provides examples of some of the potential research questions that might be addressed by such trials:

• 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 packaged compared to each other.
• 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).

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 PD/PI and NIH staff will negotiate a final list of milestones for each year of support.

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 recommends that the UG3 planning milestones have been successfully met, that the UH3 phase can proceed with confidence of success, continued relevance to the funding agency, and availability of funds.

Additional Information

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 Coordinating Center are 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 are comprised of individuals from the Demonstration Projects, the Coordinating Center, and staff from the NIH, DoD, and VA.

The Pain Management Collaboratory Coordinating Center has established a Steering Committee to address issues that span all projects, provide input into the policies and processes of the NIH-DoD-VA Pain Management Collaboratory, and assist in dissemination of policies and processes that enable research in health care systems 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 PMC Coordinating Center, Program Officers and Project Scientists from the NIH, DoD, and VA, and representatives from various NIH ICs, DoD, and the VA. All members are expected to actively participate in all Steering Committee activities. The combined vote of NIH, DoD, and VA membership may never exceed 40 percent.

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 non-responsive and will not be reviewed:

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

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

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

Section II. Award Information

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this 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 Institutions) are not eligible to apply.

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

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

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their 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 underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

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

Key Personnel of the NIH-VA-DoD Pain Management Collaboratory Coordinating Center must not be named as key personnel on applications submitted in response to this NOFO

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per 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 except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

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

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

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

The letter of intent should be sent to:

Jessica McKlveen, Ph.D.
Telephone: 301-594-8018
Email: jessica.mcklveen@nih.gov

Page Limitations

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

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

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

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

All instructions in the SF424 (R&R) 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 SF424 (R&R) 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% 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 NIH-DoD-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 NIH-DoD-VA Pain Management Collaboratory steering committee meeting in the greater Washington D.C. area.

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

To clearly distinguish between the two phases, applicants should specify separate UG3 and UH3 information in each subsection (Specific Aims and Research Strategy) of the PHS 398 Research Plan as appropriate. Activities in both phases will depend on the specific study (e.g.., disease domains, type of interventions, experimental design, randomization strategy and proposed outcome measures).

In preparing the application, investigators should consider the fact that applications will be assigned a single impact score for both UG3 and UH3 phases.

Specific Aims: Applicants should address the scientific questions to be answered, what specifically will be done during the proposed funding periods and the impact of addressing the research question on public health. Specific aims should be scientifically appropriate for the distinct phases of the project. Within in the designated page limit, include separate aims for both the UG3 and UH3 phase, 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 pain management 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 nonpharmacologic approaches for pain management and comorbidities in U.S. Veterans, military personnel, and their families. 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; and design and conduct of large-scale pragmatic trials and/or implementation science within a HCS network serving military personnel, Veterans, and their families (including using electronic health records 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 specific 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 Collaboratory Work Groups and comply with policies and practices developed by the Work Groups, and to work with the Coordinating Center 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 Institutes encourage the use of common data elements (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 outlines 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 healthcare within their organization. The letters must also relate a willingness to adopt and implement the proposed Resources and Data Sharing Plan and Software Sharing Plan.

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

NIH-DoD-VA Pain Management Collaboratory Resources, Data, and Software 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 Coordinating Center 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 plans implementation
• Promoting the use of common data elements across Demonstration Projects.
• Harmonizing, as appropriate, data elements to create opportunities for combined datasets across projects for cross-project analyses.
• Identification and creation of a PMC Data Sharing Collections repository destination by working with an NIH approved, reputable repository.

Other Plan(s): Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

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

• 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.

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

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

PHS Human Subjects and Clinical Trials Information

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

PHS Assignment Request Form

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

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

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

4. Submission Dates and Times

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

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH 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 SF424 (R&R) Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this 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 SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

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

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

Post Submission Materials

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

Any instructions provided here are in addition to the instructions in the policy.

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 announcement, note the following:

This NOFO includes Additional Review Criteria on Milestones which require comment by reviewers, and which are to be considered when determining the overall impact score. 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).

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 on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

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

3. Anticipated Announcement and Award Dates

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

Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

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

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

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

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

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

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

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

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

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

2. Administrative and National Policy Requirements

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

• Federal-wide Standard Terms and Conditions for Research Grants
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

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

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS will be required to complete an HHS Assurance of Compliance form (HHS 690) in which the recipient agrees, as a term and condition of receiving the grant, to administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, age, sex and disability, and agreeing to comply with federal conscience laws, where applicable. This includes ensuring that entities take meaningful steps to provide meaningful access to persons with limited English proficiency; and ensuring effective communication with persons with disabilities. Where applicable, Title XI and Section 1557 prohibit discrimination on the basis of sexual orientation, and gender identity. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html.

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

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

• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including providing program access, reasonable modifications, and to provide effective communication, see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html.

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

• For guidance on administering programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

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

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

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

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

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

• Overseeing the overall budget, activities and performance of the Demonstration Project.
• The PD(s)PI(s) is (are) expected to participate in all meetings of the NIH-DoD-VA Pain Management Collaboratory Steering Committee as a voting member. The PD(s)/PI(s) compile(s) for the Steering Committee and NIH, DoD, and VA Program Directors regular reports of accomplishments and roadblocks, as well as conference and meeting summaries, CC performance reports, and other reports as needed and requested.
• In addition, the PD(s)/PI(s) will identify study team members with relevant expertise that will participate in program-wide Work Groups and subcommittees.
• The PD(s)/PI(s) is (are) expected to cooperate with the NIH-DoD-VA Pain Management Collaboratory Steering Committee, research partners, and NIH-DoD-VA staff in the design and conduct of protocols, analysis of data, and reporting of results of research undertaken by the Pain Management Collaboratory Coordinating Center on behalf of the program.
• The PD(s)/PI(s) will agree to accept the participatory and cooperative nature of the collaborative research process and will comply with policies and practices developed by the NIH-DoD-VA Pain Management Collaboratory Work Groups, and to work with the Coordinating Center 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.
• Sharing data, resources and software according to the approved sharing policies for the NIH-DoD-VA Pain Management Collaboratory program and consistent with NIH sharing policies.
• Agreeing to accept close coordination, cooperation, and management of the project with NIH, DoD, and VA, including those outlined under "NIH, DoD, and VA Responsibilities"
• Submitting periodic progress reports, including materials for the In Progress Review (IPR) in a standard format, as agreed upon by the Steering Committee, and the NIH, DoD, and VA.
• 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, DoD, and VA policies and achieving the goals of this program.
• Recipient(s) agree to the governance through a Steering Committee. An NIH-DoD-VA Pain Management Collaboratory program Steering Committee will be established to address issues that span all projects, provide input into the policies and processes of the NIH-DoD-VA Pain Management Collaboratory, and assist in dissemination of policies and processes that enable research in partnership with health care systems, their patients, and practitioners.

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.
• The NIH reserves the right to terminate or curtail the award (or an individual component of the award) in the event of inadequate progress or data reporting.
• 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, DoD and 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 NIH-DoD-VA Pain Management Collaboratory research projects.
• The PD(s)/PI(s) agrees to the governance through a Steering Committee. An NIH-DoD-VA Pain Management Collaboratory Steering Committee has been established to address issues that span all projects, provide input into the policies and processes of the NIH-DoD-VA Pain Management Collaboratory, and assist in dissemination of policies and processes that enable research in partnership with health care systems, 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 PMC Coordinating Center; Program Officers and Project Scientists from the NIH, DoD, and 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 non-voting member of the Steering Committee. Each Project Scientist will have a vote. In the event that any of the federal agencies involved (NIH, DoD, and VA) have more than one Project Scientist serving on the steering committee, the Project Scientist will have a collective vote representing each agency.
• Participation in the NIH-DoD-VA Pain Management Collaboratory Work Groups are 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 Coordinating Center staff and open to participation by individuals from all funded Demonstration Projects, the Coordinating Center, and the NIH, DoD, and VA.
• Demonstration Project recipients will work with the Coordinating Center and NIH, DoD, and VA through all phase of their projects, including the research execution and close out 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 Coordinating Center with all NIH-DoD-VA Pain Management Collaboratory program resources.
• All Recipients and NIH, DoD, and VA will cooperate to ensure the timely and broad dissemination of all NIH-DoD-VA Pain Management Collaboratory program endorsed policies and practices and lessons learned in the program, to inform researchers and health care systems engaged in research in health care settings.

Dispute Resolution:

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

3. Data Management and Sharing

Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.

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.

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 Coordinating Center in the following areas:

• Development of data management and sharing plan for Demonstration Projects prior to application and best practices for data sharing across the PMC.
• Consultations related to the project data management and sharing plan implementation
• Promoting the use of common data elements across Demonstration Projects.
• Harmonizing, as appropriate, data elements to create opportunities for combined datasets across projects for cross-project analyses.
• Identification and creation of a PMC Data Sharing Collections repository destination by working with an NIH approved, reputable repository.

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.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH 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 45 CFR Part 75.301 and 2 CFR Part 200.301.

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

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

Section VII. Agency Contacts

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

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

Finding Help Online: 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: GrantsInfo@nih.gov (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: support@grants.gov

Peter Murray, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-496-4054
Email: peter.murray@nih.gov

Elizabeth L. Neilson, PhD, MPH, MSN
Office of Disease Prevention (ODP)
Phone: 301-827-5578
Email: Elizabeth.Neilson@nih.gov

Karen A. Kehl, PhD, RN
National Institute of Nursing Research
Telephone: 301-594-8010
Email: karen.kehl@nih.gov

Jessica McKlveen, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-594-8018
Email: jessica.mcklveen@nih.gov

Debbie Chen
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-594-3788
Email: debbie.chen@nih.gov

Kelli Oster
National Institute of Nursing Research (NINR)
Telephone: 301-594-2177
Email: osterk@mail.nih.gov

Section VIII. Other Information

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

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