National Institutes of Health (NIH)
National Center for Complementary and Integrative Health (NCCIH)
October 28, 2021 - Reminder: FORMS-G Grant Application Forms & Instructions Must be Used for Due Dates On or After January 25, 2022 - New Grant Application Instructions Now Available. See Notice NOT-OD-22-018.
• September 13, 2021 - Updates to the Non-Discrimination Legal Requirements for NIH Recipients. See Notice NOT-OD-21-181.
• August 5, 2021 - New NIH "FORMS-G" Grant Application Forms and Instructions Coming for Due Dates on or after January 25, 2022. See Notice NOT-OD-21-169
• August 5, 2021 - Update: Notification of Upcoming Change in Federal-wide Unique Entity Identifier Requirements. See Notice NOT-OD-21-170
• April 20, 2021 - Expanding Requirement for eRA Commons IDs to All Senior/Key Personnel. See Notice NOT-OD-21-109: Expanding Requirement for eRA Commons IDs to All Senior/Key Personnel (nih.gov)
The purpose of this FOA 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 (PMC) 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 health care system (HCS)-focused research including assistance to UG3/UH3 grant awardees.
February 15, 2022
|Application Due Dates||Review and Award Cycles|
|New||Renewal / Resubmission / Revision (as allowed)||AIDS||Scientific Merit Review||Advisory Council Review||Earliest Start Date|
|March 15, 2022||Not Applicable||Not Applicable||June 2022||August 2022||September 2022|
All applications are due by 5:00 PM local time of applicant organization.
Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide,except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts ).
Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.
Applications that do not comply with these instructions may be delayed or not accepted for review.
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 veterans 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 are often 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, DOD, and 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 U.S. Department of Veterans Affairs (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 Department of Defense (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 as well as a Coordinating Center.
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 willcut 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.
The purpose of this FOA 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 (PMC) 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 awardees.
The second wave of the NIH-DOD-VA Pain Management Collaboratory solicited under the FOA will:
Demonstration Projects funded through this FOA will be expected to work collaboratively with the Pain Management Collaboratory Coordinating Center (PMC3) and the other PMC projects funded under the first wave of PMC trials as well as those funded under this FOA. 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 FOA 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. The UG3/UH3 application must be submitted as a single application, following the instructions described in this FOA.
All Demonstration Projects should address a question important to the health of U.S. military personnel, veterans and their families that is focused on nonpharmacologic approaches to pain management and, if applicable, comorbid 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 purposes of this FOA, 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 of lower programmatic priority.
The research question(s) proposed should be of major public health importance focusing on nonpharmacologic approaches to pain management and comorbid conditions in military personnel, veterans and their families – and one that will engage partnership with health care delivery systems providing services to this population. 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 interventions of known efficacy which have not yet been evaluated for effectiveness in the VA and/or DOD health care settings. 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. Applicants are encouraged to review 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/ to avoid submitting a trial that overlaps significantly with other on-going or completed trials testing methods to manage pain in U.S. military personnel, veterans and their families.
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 will need to 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 comorbid conditions or 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 active-duty service members, veterans 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.
For projects proposing implementation science aims:
Outcomes of implementation trials should focus on rigorous assessment and outcomes of the strategies employed 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.
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:
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:
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 FOA 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.
Applicants who propose effectiveness aims should address one or more critical research questions to improve pain management 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 pragmatic trials:
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:
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:
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 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 NIH, and availability of funds.
Governance: The awards funded under this FOA and the companion FOAs 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, 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 healthcare 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 FOA
The following types of research are not responsive to this FOA and applications proposing such activities will be deemed non-responsive and will not be reviewed:
See Section VIII. Other Information for award authorities and regulations.
Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.
Required: Only accepting applications that propose clinical trial(s).
The NCCIH intends to commit up to $4,500,000 in FY2022 to support up to 6 UG3 Research Planning Phase awards contingent upon receiving scientifically meritorious applications.
The application budget for the UG3 phase is limited to $500,000/year in direct costs. Costs for each year of the UH3 phase are limited to $1,000,000/year in direct costs.
The UG3 phase is limited to one year and the UH3 phase can request up to four years of support. The total project period for an application submitted in response to this FOA may not exceed 5 years.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.
1. Eligible Applicants
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
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 must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
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.
2. Cost Sharing
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
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 188.8.131.52 Submission of Resubmission Application. This means that the NIH will not accept:
1. Requesting an Application Package
The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.
2. Content and Form of Application SubmissionIt is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.
Letter of Intent
Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.
By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:
The letter of intent should be sent to:
Martina Schmidt, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed, with the following exceptions or additional requirements: For this specific FOA, the Research Strategy section is limited to 30 pages.
Instructions for Application Submission
The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.
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.
Facilities and Other Resources: The application should provide sufficient rationale for the HCS(s) selected for the Demonstration Project. Applicants should provide a description of successfully conducted clinical studies within the partnering HCS, and describe the infrastructure and expertise (e.g., clinical investigators, informaticists) to implement the proposed pragmatic trial within all proposed HCSs.
SF424(R&R) Senior/Key Person Profile
All instructions in the SF424 (R&R) Application Guide must be followed.
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 military and veteran health care delivery organizations. The experience of the investigative team with successful recruitment and retention of participants should be described.
All instructions in the SF424 (R&R) Application Guide must be followed.
Budgets for both phases (UG2/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 senior and junior 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. Additionally, applications must budget for an in-person kick-off meeting to be held in the first year 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. military personnel, veterans 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 on 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.
The following modifications also apply:
NIH, DOD, and VA consider the sharing of unique research resources developed through NIH, DoD, and VA-sponsored research an important means to enhance the value of, and advance research. If the final data/resources are not amenable to sharing, this should be explained in the proposed Sharing Plans. The NIH-DOD-VA Pain Management Collaboratory program encourages sharing of resources with broad availability of policies, practices, materials, and tools to facilitate collaboration, reuse, and replication. In addition, the NIH-DOD-VA Pain Management Collaboratory program encourages sharing of study data from Demonstration Projects in a timely manner with appropriate privacy and confidentiality protections to facilitate further research, reuse of data, and replication. Thus, the NIH-DOD-VA Pain Management Collaboratory program expects grantees to implement a Data Sharing Plan consistent with achieving these program goals. A Data Sharing Plan is expected to be included in the application.
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
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.
Section 2 - Study Population Characteristics
2.4 Inclusion of Women and Minorities
Describe strategies for outreach, recruitment and retention of minorities and women. In accordance with NIH policy, studies proposing phase III trials are required to report analysis of sex/gender, and race and/or ethnicity group differences in primary outcomes (https://grants.nih.gov/policy/inclusion/women-and-minorities.htm).
2.5 Recruitment and Retention Plan
Describe the following: 1) the planned recruitment methods, including use of contact lists (participants and/or sites), databases or other pre-screening resources, advertisements, outreach, media / social media and referral networks or groups; 2) if there are known participant or study-related barriers to accrual or participation (based on literature or prior experience), please list these barriers and describe plans to address them to optimize success; 3) contingency plans for participant accrual if enrollment significantly lags behind accrual milestones; 4) participant retention and adherence strategies; and 5) possible competition from other trials for study participants.
Applicants must provide strong evidence of the availability of appropriate institutional resources, and suitable patient populations, providers, clinics, or facilities (depending on unit of randomization). Documentation of availability of eligible participants, clinic sites, or unitsof randomization, presented in tabular format must be provided. The application must include relevant information that addresses the feasibility of recruiting participants who are eligible for the pragmatic or implementation trial. Specifically, applicants must provide evidence that each recruiting center in the trial has access to a sufficient number of participants who meet the eligibility criteria as defined in the submitted protocol. For multisite applications, information must be provided for each participating site.
2.7 Study Timeline
Include a table or graph of the overall study timeline. This is expected to be a visual representation (such as a Gantt chart) of core milestones and key project management activities. A narrative is not expected in this section.
The study timeline should include core milestones that need to be met throughout the lifecycle of the clinical trial (to include both the UG3 and UH3 phases) to ensure its success, and the subtasks that will be used to reach the milestones. In the timeline, the study duration is expected to be displayed in months. The timeline should include, but is not limited to, the following:
(a) When the study opens to enrollment
(b) When core milestones (see below) are met
(c) What subtasks are needed to reach the core milestones
(d) When final transfer of the data will occur
(e) When analysis of the study data will occur
Section 3 - Protection and Monitoring Plans
3.3 Data and Safety Monitoring Plan
In addition to the NIH application requirements for data and safety monitoring for clinical trials, applicants should refer to NIH’s policy on data and safety monitoring (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html).
Section 4 - Protocol Synopsis
4.1.a. Detailed Description
Describe the protocol to be followed in each arm of the trial. Include a brief description of how the trial will standardize the intervention and whether there are any plans to intervene to improve adherence to the intervention at the sites. Specify concomitant interventions, if applicable. Describe the proposed experimental design, including a discussion of the clinical trial design and the rationale for the particular design chosen (pragmatic, explanatory, cluster-randomized, adaptive, etc.).
4.7 Dissemination Plan
Describe how the investigators will facilitate and support timely publication and dissemination of results and developed tools as appropriate and consistent with achieving the goals of the program.
Section 5 - Other Clinical Trial-related Attachments
5.1 Other Clinical Trial-related Attachments
The following attachments must be included as a part of the cooperative agreement application. Attachments permit expansion of certain elements that cannot be appropriately described in the Research Strategy. All attachments listed below must be provided or the application will not be peer reviewed.
1. Clinical Trial Experience
Applicants must provide a detailed table listing the characteristics of trials that demonstrate Key Personnel experience in trial coordination in the last 5 years. The table must be provided as an attachment called "Clinical Trial Experience.pdf", appended with 1, 2, 3, etc. as needed, and must not exceed 3 pages.
The table columns should include:
2. Milestone Plan
A Milestone Plan must be provided as an attachment called "Milestone Plan.pdf" and must not exceed five pages.
The milestones should be well described, quantifiable, and scientifically justified to allow an assessment of progress. For UG3 milestones, applicants should delineate what they propose to achieve in order to proceed to the UH3 phase. The milestones should also include a timeline, a discussion of the suitability of the milestones for assessing success in the UG3 Phase, and a discussion of the implications of successful completion of these milestones for the proposed UH3 Phase. Annual milestones for the Project trial conduct phase (UH3) should also be included in the application, although it is understood that timelines and milestones for conduct of the trial in the UH3 phase that are proposed in the application will evolve as activities in the UG3 phase progress, if an Award is made.
All applicants must use the following definition of a milestone in their application: a scheduled event in the project timeline that signifies the completion of a major project stage or activity. Milestones must be relevant, achievable, and measurable. Milestones should address overall recruitment and retention goals. The Terms and Conditions under this FOA will include a milestone plan that is mutually agreed upon by the investigators and NIH.
Delayed Onset Study
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.
PHS Assignment Request Form
All instructions in the SF424 (R&R) Application Guide must be followed.
3. Unique Entity Identifier and System for Award Management (SAM)
See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov
4. Submission Dates and Times
Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
5. Intergovernmental Review (E.O. 12372)
This initiative is not subject to intergovernmental review.
6. Funding Restrictions
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
7. Other Submission Requirements and Information
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.
All PD(s)/PI(s) must include their eRA Commons ID in the Credential fieldof the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.
The applicant organization must ensure that the unique entity identifier (DUNS number or UEI as required) provided on the application is the same number 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 NCCIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.
Studies proposing basic/mechanistic studies or efficacy studies will not be reviewed.
In order to expedite review, applicants are requested to notify the NCCIH Referral Office by email at SchmidMa@mail.nih.gov when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.
Post Submission Materials
Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.
All post-submission materials must be received by the Scientific Review Officer (SRO) no later than 30 calendar days prior to the peer review meeting. In addition to the NIH policy allowed post-submission materials in NOT-OD-19-083, the follow post-submission materials are allowed:
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 FOA includes Additional Review Criteria on Milestones which require comment by reviewers, and which are to be considered when determining the overall impact score. In addition, this FOA includes additional review considerations on Data Sharing, which will be considered by reviewers but will not be scored individually or influence the overall impact score. This FOA 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.
Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?
Specific to this FOA: Does the application provide rationale to indicate that the proposed intervention(s) have sufficient evidence to move to this stage of research? Is the proposed trial addressing a major public health issue focused on nonpharmacologic approaches to pain management and comorbidities in U.S. military personnel, veterans and their families? How will the completion of the proposed trial change the concepts, methods and technologies used in pain management research and/or care?
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?
With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?
Specific to this FOA: Do interdisciplinary teams include necessary expertise to conduct the trial? For example, do PD(s)/PI(s) have experience conducting pragmatic and/or implementation research trials within health delivery organizations? Do the PD(s)/PI(s) and key personnel have the necessary expertise in design and implementation of large-scale effectiveness and/or implementation trials within a HCS network serving military personnel, veterans, and their families? For example, do they have expertise in using electronic health records for recruitment and outcomes assessment? Lastly, are VA researchers included on veteran-focused applications?
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?
Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?
Specific to this FOA: Does the application challenge and seek to impact current conventional approaches to research and/or practice by utilizing novel approaches or methodologies for a trial that will allow it to be successfully implemented in a DOD/VA environment? Does the application include mechanisms for leveraging novel collaboration and study oversight strategies?
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?
If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?
Does the application adequately address the following, if applicable
Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?
Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?
Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?
Data Management and Statistical Analysis
Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?
Specific to this FOA: Will proposed planning activities (including plans for identifying a sufficiently large target patient population), allow for implementing the Demonstration Project? Are rigorous and appropriate controls included in the design? Will broad but adequate eligibility criteria be used, as proposed? How will the approaches proposed overcome barriers and activate facilitators in the HCS setting? Are the goals of the UG3 research planning phase reasonable and if accomplished will they provide the basis for the proposed UH3 research execution phase?
Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?
If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?
Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?
If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?
If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?
Specific to this FOA: Does the application provide sufficient rationale for the HCS(s) selected for the Demonstration Project? Has/have the HCS(s) successfully conducted similar research, such that there are sufficient infrastructure and expertise (e.g., clinical investigators, informaticists) to implement the proposed trial within all proposed HCSs?
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.
Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?
Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?
For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
Are the steps and milestones clearly defined? Are the milestones feasible, well developed and quantifiable with regard to specific goals and accomplishments? Are adequate criteria provided for the UG3 phase that will be utilized in determining milestone completion before proceeding to the next phase of the project? Are the UH3 milestones appropriate for the research execution phase of the project?
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.
Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).
How strong are the letters from the officials responsible for intellectual property issues at the applicant institutions (including sub-contractor institutions) stating that the institution supports and agrees to abide by compliance with the Resource Sharing Plan?
Is sharing of manuals and clinical tools across different institutions feasible and appropriate?
For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
2. Review and Selection Process
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NCCIH, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.
As part of the scientific peer review, all applications will receive a written critique.
Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.
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.
1. Award Notices
If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.
Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.
Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.
ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm
Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.
Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).
Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).
2. Administrative and National Policy Requirements
All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:
If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.
Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex (including gender identify, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html
HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.
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:
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
Areas of Joint Responsibility include:
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 awardee. This special dispute resolution procedure does not alter the awardee'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.
When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.
A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over the threshold. See the NIH Grants Policy Statement for additional information on this reporting requirement.
In accordance with the regulatory requirements provided at 45 CFR 75.113 and 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 and 2 CFR Part 200 – Award Term and Condition for Recipient Integrity and Performance Matters.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Peter Murray, PhD
National Center for Complementary and Integrative Health (NCCIH)
Martina Schmidt, Ph.D.
National Center for Complementary & Integrative Health (NCCIH)
National Center for Complementary and Integrative Health (NCCIH)
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.
Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.