Part 1. Overview Information

Key Dates

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

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

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

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

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

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to support multi-site clinical trials in geographically diverse school settings to test the efficacy or effectiveness of complementary and integrative health approaches with physical and/or psychological therapeutic inputs (often called mind and body interventions) to promote mental, emotional, and behavioral (MEB) health and prevent MEB disorders among youth. The overall goal of this FOA is to provide support for a set of multisite trials to improve the evidence base of complementary and integrative health approaches that can be delivered in a school-based setting or with students to address the youth mental health crisis. Awards made under this FOA will support a milestone-driven planning phase (UG3) for one year with possible transition to a study conduct phase (UH3) of up to an additional four years. Total duration of the award will be a maximum of 5 years. Only UG3 projects that meet the scientific milestones and feasibility requirements will transition to the UH3 phase. The UG3/UH3 application must be submitted as a single application describing both phases and instructed in this FOA.

Background

Promotion of good mental health and addressing mental health disorders in children and adolescents (hence, youth) are urgent public health priorities. In December 2021, the U.S. Surgeon General, Dr. Vivek H. Murthy, called for immediate action to address the growing youth mental health crisis that has worsened with the COVID-19 Pandemic. The recent February 2022 Morbidity and Mortality Weekly Report (MMWR), Mental Health Surveillance Among Children – United States, 2013-2019, from the Centers for Disease Control and Prevention (CDC) documents the high prevalence of mental health disorders among U.S children prior to the pandemic. The MMWR findings revealed that mental health disorders can begin in early childhood, and mental disorders and receipt of mental health services increased with age. Additionally, mental health disorders and poor mental health posed a greater burden in some groups of children including LGBT youth, youth from racial and ethnically minoritized populations, youth from low-income backgrounds, and youth with disabilities and chronic conditions. Other national surveys of youth have for example indicated that prior to the COVID-19 pandemic, mental health challenges were the leading cause of disability and poor life outcomes in youth with up to 1 in 5 children ages 3 to 17 in the U.S. with a reported mental, emotional, developmental or behavioral disorder. These surveys have also revealed increases in depressive symptoms and suicidal ideation. For example, in 2019, 1 in 3 high school students reported persistently feeling sad or hopeless in the past year and estimates from the National Center for Health Statistics suggest there were more than 6,600 deaths by suicide among youth ages 10-24 in 2020.

Given these alarming surveillance findings, research is needed on health promotion and risk prevention approaches to reduce the incidence and prevalence of mental, emotional, and behavioral (MEB) disorders among youth. MEB disorders contribute to high rates of disability, school dropout, cardiovascular and metabolic diseases, lost years of productivity, incarceration, and homelessness. Evidence-based strategies including contemplative practices such as mindfulness-based interventions and yoga may be important for promoting MEB health and to assist youth with developing resilience to manage health risks such as bullying, substance use, depression, anxiety, and suicidal thoughts. Other research opportunities of complementary and integrative health approaches to improve the MEB health of youth that warrant exploration can include addressing mental health stigma, reducing conflict, improving stress management, and promoting violence prevention (e.g. reducing bullying/cyberbullying).

In fact, a key research priority identified in the 2019 National Academies of Sciences, Engineering, and Medicine report, Fostering Healthy Mental, Emotional, and Behavioral Development in Children and Youth: A National Agenda, is a call for the design, evaluation, and implementation of effective school-based interventions to promote healthy MEB development at the population level. Examples of specific research targets noted for investigation are mechanisms to support social-emotional learning including mindful awareness approaches, rigorous trials of school-based interventions for youth and their impact on social, cognitive, and emotional learning, and delivery methods of a multitiered system of support in all K-12 schools to coordinate the implementation of evidence-based universal, selective, and indicated prevention interventions.

Schools have increasingly become key access points of MEB health services for youth and have the capacity to reach large populations of children at different developmental time periods. This is especially relevant for underserved racial and ethnic minority youth from low socioeconomic status (SES) backgrounds who experience greater vulnerability for health risks as a result of disproportionate psychosocial disparities (poverty; barriers to health and mental health services) and exposure to multiple stressors (psychological trauma; structural racism; discrimination; community violence; immigration), who are more likely to have unmet mental health service needs. Although research in school settings is limited, mindfulness-based interventions and yoga hold promise for enhancing the social-emotional resiliency among youth. Mindfulness training has been shown to improve self- regulation in adolescents which has led to improvements in academic achievement, substance use, behavior problems, and mental health. Likewise, preliminary evidence indicates that yoga may reduce behavioral and emotional difficulties in youth by enhancing social-emotional competencies such as self-regulation and self-awareness. However, the methodological limitations of existing research including small sample sizes, lack of implementation fidelity monitoring, use of non-experimental research designs, and lack of control conditions, and not addressing clustering, group delivered intervention, or shared intervention provider with appropriate statistical approaches warrant a need for rigorous multisite trials to build the evidence base for the effectiveness of complementary and integrative health approaches with physical and/or psychological therapeutic inputs (often called mind and body interventions) to promote MEB health and prevent MEB disorders among youth.

Research Objectives

This FOA supports UG3/UH3 phased cooperative research of multisite clinical trials conducted in geographically diverse school settings to assess the efficacy or effectiveness of complementary and integrative health approaches with physical and/or psychological therapeutic inputs (often called mind and body interventions) to promote MEB health and prevent MEB disorders among youth. Awards made under this FOA will initially support a one-year milestone-driven planning phase (UG3), with possible transition to a trial conduct phase (UH3). 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.

A priority for NCCIH is expanding research on health promotion and restoration, resilience, disease prevention, and symptom management. Thus, applications that include a focus on strategies to support multicomponent approaches to examine MEB health and the impact on the whole child including MEB, academic and physical health outcomes (e.g., sleep disturbances, obesity, physical activity) are encouraged. Projects can also consider sustainability - startup and maintenance cost of intervention, ROI/return on investment, and the resources (including partnerships) needed for scaling and maintaining benefits of proposed interventions.

Projects are encouraged to provide a conceptual model that describe hypothesized causal pathways by which complementary and integrative health approaches with physical and/or psychological therapeutic inputs (often called mind and body interventions) promote MEB health and prevent MEB disorders among youth. Additionally, projects can involve primary data collection and can be augmented with available administrative or secondary datasets (e.g., U.S. Department of Education data, school records, U.S. census tract/neighborhood data, Electronic health record data).

Projects that focus on reducing health disparities and advancing equity in MEB health among youth from NIH-designated health disparity populations (i.e., Blacks/African Americans, Hispanics/Latinos, American Indians/Alaska Natives, Asian Americans, Native Hawaiians and other Pacific Islanders, socioeconomically disadvantaged populations, underserved rural populations, and sexual and gender

minorities) and other vulnerable populations (e.g., children with disabilities, homeless youth) are of high interest.

Projects should seek to involve collaborations from relevant stakeholders (e.g., Department of Education, health service providers and systems, department of social services, Federally Qualified Health Centers, academic partners, community-based organizations, faith-based organizations, Department of Juvenile Justice, national parent teacher associations) as appropriate to facilitate a better understanding of the MEB needs of youth, tracking of outcomes, and evaluation of risk and protective factors for youth MEB health.

The proposed trials must meet all the following criteria:

• The project must include a complementary or integrative health intervention
• The project must study MEB in youth in school settings or identify youth at schools and then provide after school or telehealth delivered intervention for youth.
• The project must test an intervention, or coordinate several interventions (which can be treatments, preventive actions, or organizational changes) that are robust, apply to the prevention or treatment of MEB in youth and are suitable for use in school settings, with the broad goal of determining whether the intervention(s) is efficacious or effective.
• The intervention(s) must be well-characterized and available such that it could be reliably delivered in school settings.
• The intervention(s) must be reasonably simple and not require a complex structure for implementation or monitoring.
• The outcome measure(s) must be related to MEB and clinically meaningful and important to stakeholders including youth, parents, teachers, and school administrators.
• The project design must incorporate rigorous controls, prospectively identified, preferably by randomization. The design may incorporate novel randomization approaches, such as by cluster or timing of implementation. If another method is used to generate the comparison group, perhaps by staged assignment or staged implementation of the intervention, it should provide comparable rigor.
• Proposed analytic plans for projects that proposed cluster-randomized trials must address adequacy of sample size and study power and employ analytic strategies relevant for such trial designs. Applicants are strongly encouraged to consult Collaboratory Biostatistical Guidance documents (http://sites.duke.edu/rethinkingclinicaltrials/biostatistical-guidance-documents/) when developing cluster-randomized trial analytic plans.
• The project must enroll youth based on broad eligibility criteria to maximize diversity, and minimize intentional or unintentional exclusions based on risk, health literacy, demographics, or expected adherence.
• Milestones for proposed trials must be appropriate (i.e., relevant, measurable, achievable, result-focused, and timebound) and a contingency plan must be provided in the event UG3 and/or UH3 milestones are not achieved.

Applications NOT Responsive to this FOA

• Projects that are conducted in a single school
• Projects that are exclusively qualitative or observational
• Studies to assess initial feasibility of an intervention.
• Studies that propose to conduct studies in animals or in vitro studies.
• Drug or device safety trials.
• Applications proposing to study botanical products, dietary supplements or other non-FDA approved medications
• Projects that include prohibited policy lobbying or advocacy activities (see https://grants.nih.gov/grants/lobbying_guidance.htm for more information).
• Projects that examine the financing of health care or the cost and efficiency of health care service delivery, without linking such economic analysis to measurable health outcomes (See NOT-OD-16-025 for more information).

Non-responsive applications will not be reviewed. Applicants are strongly encouraged to reach out to the relevant scientific contacts to discuss whether their applications are responsive.

IC-Specific Areas of Interest

For NCCIH, areas of interest include, but are not limited to:

• Randomized efficacy or effectiveness trials of complementary and integrative health approaches to promote MEB health and prevent MEB disorders among youth. Complementary approaches include those with physical and/or psychological therapeutic inputs, often called mind and body approaches (e.g., yoga, tai chi, qi gong, meditation, mindfulness-based interventions, hypnosis, music therapy, art therapy, acupuncture, spinal or chiropractic manipulation, and massage) as well as approaches with nutritional therapeutic inputs (e.g., special diets). Integrative approaches include therapies that combine complementary approaches with conventional medical interventions such as pharmacologic, surgery, or device-based treatments.
• Trials that will assess outcomes of MEB as well as physical outcomes such as physical functioning, sleep, and resilience.
• Trials to assess multicomponent or multilevel complementary and integrative intervention models- including tiered intervention structures- in school settings that incorporate addressing disparities of social determinants of health (SDoH) to mitigate risks of MEB disorders and promote resilience.
• Trials to assess the impact of multi-scale interventions that target students, parents, teachers, and or school administrators and staff. Outcomes in these trials could include system level measures such as rates of expulsion/disciplinary consequences, absenteeism, graduation, and overall school climate.
• Examination of complementary and integrative health interventions to address unmet mental health service needs.
• Trials to assess telehealth implementation models of complementary and integrative health approaches to enhance MEB outcomes for youth.
• Trials to assess complementary and integrative approaches to assist youth with management of exposures to social media and interactions (e.g., cyberbullying) with digital technology that can confer risk for MEB disorders and negatively impact whole health and well-being.
• Testing of cultural and contextual adaptations of complementary and integrative health approaches to address MEB outcomes including potential disparities.
• Trials to assess the differential impact of complementary and integrative approaches to address MEB health disparities for at risk youth such as sexual and gender minority youth, immigrant youth, youth with disabilities, youth who reside in rural areas, and youth involved in the juvenile justice system.
• Secondary outcomes can include examination of the mechanisms by which complementary and integrative health approaches improve academic and MEB health outcomes for youth. However, collection of the mechanistic outcomes should be streamlined and not interfere with the conduct of the trial’s goal to assess the primary outcome of MEB health.
• Trials of complementary and integrative health intervention models to address immediate and long-terms effects of COVID-19 pandemic and other public health emergencies (e.g., community violence/school shootings) on the MEB health of youth.

Office of Disease Prevention (ODP)

The ODP is the lead office at the NIH responsible for assessing, facilitating, and stimulating research in disease prevention. In partnership with the 27 NIH Institutes and Centers, the ODP strives to increase the scope, quality, dissemination, and impact of NIH-supported prevention research. The ODP co-funds research that has strong implications for disease and injury prevention and health equity and that includes innovative and appropriate research design, measurement, and analysis methods. The ODP has a specific interest in projects that develop and/or test preventive interventions. For this RFA, the ODP is interested in co-funding clinical trials in geographically diverse school settings to test the efficacy or effectiveness of interventions that promote mental, emotional, and behavioral (MEB) health and prevent MEB disorders among youth. Projects that focus on reducing health disparities and advancing equity in MEB health among youth from NIH-designated health disparity populations (i.e., Blacks/African Americans, Hispanics/Latinos, American Indians/Alaska Natives, Asian Americans, Native Hawaiians and other Pacific Islanders, socioeconomically disadvantaged populations, underserved rural populations, and sexual and gender minorities) and other vulnerable populations (e.g., children with disabilities, homeless youth) are of interest.

The ODP provides co-funding, but does not award grants. Applications must be relevant to the objectives of NCCIH. Please reach out to the NCCIH contact listed for questions regarding research priorities and funding. ODP only accepts co-funding requests from NIH Institutes and Centers (ICs). For additional information about ODP, please refer to the ODP Strategic Plan for Fiscal Years 2019–2023.

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

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

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

Federal Governments

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

Other

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

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

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

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

Applicant Organizations

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

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

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

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

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support.

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.

3. Additional Information on Eligibility

Number of Applications

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

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

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

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

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

Letter of Intent

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

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

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

The letter of intent should be sent to:

Martina Schmidt, PhD
Chief, Office of Scientific Review
National Center for Complementary and Integrative Health
Telephone: 301-594-3456
Email: [email protected]

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed, with the following additional instructions:

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

Instructions for Application Submission

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

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

The application should provide sufficient rationale for the proposed partnering school sytem(s) for the Project. Applicants should provide a description of successfully conducted clinical studies within the partnering school systems, and describe the infrastructure and expertise (e.g., clinical investigators, teacher, administrators) to implement the proposed trial.

SF424(R&R) Senior/Key Person Profile

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

Biosketches should reflect the PD(s)/PI(s) and key personnel's expertise in design and conduct of large-scale clinical trials within multiple schools including using school or administrative records for recruitment or outcomes assessment, if applicable. 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, withthe following additional instructions:

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

Application budgets must include a minimum effort for the PD/PI of 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.

Application 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 can include personnel at the partnering schools with expertise relevant to the project, which might include teachers, school nurses, administrators, and staff with expertise in the administrative aspects of conducting clinical trials within the school setting.

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. MEB 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. Include separate aims, within the designated page limit, for both the UG3 and UG3 phase, and clearly label them as UG3 specific aims and UH3 specific aims.

Research Strategy: Within the Research Strategy, applicants should first describe the UG3 Phase and then the UH3 Phase. The Research Strategy section should have a clear demarcation of the UG3 and UH3 phases of the application. It is not necessary to repeat background information or details of methods in the UH3 portion that were provided in the UG3 portion. 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 details for the proposed trial including projections for recruitment, attrition and effect size estimations.

Both the UG3 and the UH3 phases of the Research Strategy must have a section of proposed milestones, which 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.

The application should describe the school/ school system partners and the investigative team's experience conducting trials within school settings. In general, all studies must use multiple schools or school systems in at least two geographically distinct regions of the United States, unless a specific rationale for limiting this aspect of the project is provided, which must be identified in the application. The application must provide a rationale for the schools or school systems selected for the Project and provide a description of the infrastructure and expertise to implement the trial within all proposed schools or school systems.

Applicants should address how they will adhere to the NIH Policy on Good Clinical Practice Training. This policy establishes the expectation that all NIH-funded investigators and staff who are involved in the conduct, oversight, or management of clinical trials should be trained in Good Clinical Practice (GCP), consistent with principles of the International Conference on Harmonization (ICH) E6 (R2).

The principles of GCP help assure the safety, integrity, and quality of clinical trials. This Policy applies to NIH-funded investigators and clinical trial site staff who are responsible for the conduct, management and oversight of NIH-funded clinical trials (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-148.html

Applicants should not propose work that duplicates efforts already funded or underway (https://reporter.nih.gov/, https://heal.nih.gov/funding/awarded, https://www.pcori.org/explore-our-portfolio).

Although novel theoretical approaches and methodologies may be needed, when possible, applicants should leverage, adopt or adapt resources from ongoing NIH-supported efforts in informatics as well as other national efforts including but not limited to the many federal investments in the HMO Research Network, the CTSAs, REDCap, PROMIS, NIH Toolbox, Health Care Innovation Awards, DEcIDE, eMERGE, other networks, CERTs, SHARP, Vaccine Safety Datalink, PCORI, the Sentinel Initiative.

Applicants should allow flexibility in determining which patient-reported outcome measures will be used, if possible. It is anticipated that some common measures may be proposed for the set of trial supported under this FOA, so investigators should be prepared to include additional measures.

Letters of Support: Applications must include a strong letter of support from each stakeholder partner of the proposed school site(s) or school system(s) that relates their commitment to the proposed research. The letter must provide a description of how the project would directly impact delivery of intervention at the school sites and indicate level of intention to sustain the intervention(s) based upon results. The application is expected to include letters from the officials responsible for intellectual property issues at the applicant institutions (including sub-contractor institutions) stating that the institution supports and agrees to abide by the Resources and Data Sharing Plan and the Software Sharing Plan put forth in the application. These letters should be clear expressions of commitment consistent with achieving the goals of the program.

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

The following modifications also apply:

Applicants must provide a description of the resources that will be made broadly available including policies, practices, materials, and tools to facilitate collaboration, reuse, and replication of the project. Describe any plans to disseminate toolkits or other resources developed for the pragmatic or implementation trial. Applications must provide descriptions of how privacy and confidentiality will be maintained. The plan must include a description of how data will be shared to allow for transparency and reproducibility of study findings (e.g. access to data, data enclave, or data repository).

Appendix:

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. The additional instructions apply:

Section 2 - Study Population Characteristics

2.4 Inclusion of Women and Minorities

Describe strategies for outreach to minorities and women.

2.5 Recruitment and Retention Plan

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

Applicants must provide strong evidence of the availability of appropriate institutional resources. The application must include relevant information that addresses the feasibility of recruiting participants who are eligible for the trial. Specifically, applicants must provide evidence that each recruiting school site in the trial has access to a sufficient number of participants who meet the eligibility criteria as defined in the submitted protocol synopsis. 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
(f) When the primary study manuscript will be submitted for publication

Section 3 - Protection and Monitoring Plans

3.3 Data and Safety Monitoring Plan

In addition to the NIH application requirements for 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 (individual-randomized, cluster-randomized, adaptive, etc.).

Section 5 - Other Clinical Trial-related Attachments

5.1 Other Clinical Trial-related Attachments

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

1. Clinical Trial Experience

Applicants must provide a detailed table listing the characteristics of the most relevant 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 total for all key personnel in the application.

The table columns should include:

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

2. Milestone Plan

A Milestone Plan must be provided as an attachment called " Milestone Plan.pdf" and must not exceed 3 pages.

The plan should describe the key milestones that need to be met throughout the lifecycle of the clinical trial (UG3 and UH3 phases) to ensure its success, the processes that will be used to reach the milestones, and a timetable identifying when each of these key milestones will be met (this can be provided as a table or a graph).

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. The milestone plan should include anticipated challenges to meeting milestones and propose potential mitigation or corrective actions strategies. UH3 milestones should address overall recruitment and retention goals. The Terms and Conditions for a UG3 award under this FOA will include a milestone plan that is mutually agreed upon by the investigators and NCCIH.

Milestones of particular interest during the UG3 phase that should be described in the application may include but are not limited to:

• Successfully complete pilot vanguard study and meet benchmarks, if applicable
• Complete finalized clinical protocol approved by NCCIH and Protocol Review Committee/DSMB, (as applicable)
• Final informed consent form(s) and, if applicable, assent forms
• Agreements in place for trained intervention providers
• Comprehensive laboratory plan (as applicable)
• Pharmacy/laboratories identification (as applicable)
• Contracts/Third Party Agreements (if applicable)
• Training plan for school sites
• Final Management/Communication Plan
• Final Data and Safety Monitoring Plan (DSMP)
• Site Performance Plan
• Data Completeness and Quality Monitoring Reporting Plan
• Completion of regulatory approvals
• Single IRB approval for school sites with reliance agreements established
• Submission of UH3 transition request 2 months prior to the requested transition date

The application should also include a series of milestones for the completion of the specific aims of the clinical trial (UH3) phase and contingency plans. Milestones for the UH3 phase may need to be revised and finalized at the time of the UG3/UH3 transition. Investigators and NIH will review and mutually agree upon a final revised UH3 milestone plan that will be included in the Terms and Conditions of the UH3 grant (if awarded).

CCC milestones of particular interest during the UH3 phase that should be included in the application include but are not limited to:

• Target dates for enrollment of 10, 25, 50, 75 and 100 percent of the projected recruitment for all study participants, including women, minorities and children (as appropriate)
• Assessment of site(s) protocol implementation performance and fidelity of intervention delivery
• Collection of data related to primary and secondary endpoints and database lock
• Submission of primary manuscript to peer-reviewed scientific journal
• Submission of study results to ClinicalTrials.gov within 12 months of the primary completion date
• Data sharing plan for study data and biospecimens (as applicable)

During the award phase, achievement of each milestone for the UG3 and UH3 phases will need to be communicated to the NCCIH Program Officer listed on the Notice of Award. Award continuation, even during the period recommended for support, is conditional upon satisfactory progress. If, at any time, recruitment, as defined in the NCCIH Study Accrual and Retention Plan (https://nccih.nih.gov/grants/policies/SARP), falls significantly below projections, or core milestones mutually agreed upon by the PD/PI and NCCIH, are not met, the Center may consider ending support and negotiating an orderly phase-out of the award. NCCIH retains the option of periodic external peer review of progress. NCCIH staff will closely monitor progress at all trial stages, including milestones, accrual, and safety.

Delayed Onset Study

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

PHS Assignment Request Form

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

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

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

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 [email protected] when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

Requests of $500,000 or more for direct costs in any year

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.

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:

• Updated Clinical Trial Experience Table (e.g. due to updated enrollment numbers, publication of trial results, or newly started clinical trials)
• Updated Milestone Plan (e.g. due to the hiring, replacement, or loss of an investigator; change to schools or school systems participating in the trial; or change in administrative records used in the trial)

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 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, for applications involving clinical trials: 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.

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

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

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

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

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

2. Review and Selection Process

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

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

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

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

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

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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

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

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

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

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

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

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

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

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

2. Administrative and National Policy Requirements

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

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

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

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex (including gender 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.

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

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

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

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

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

The DSMB will play a crucial role in ensuring the safety and welfare of patients enrolled in the trial, will regularly review study progress and some interim data and will provide recommendations to NIH. During the award, the recipient will provide interim data and reporting, as requested, to the Board as outlined in NCCIH guidelines. The following special terms of the 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 NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH's 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 reside with the recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and NIH as defined below.

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

• Research design and protocol development, including the definition of objectives and approaches, planning, implementation, participant recruitment and follow-up, data collection, quality control, interim data, and safety monitoring, final data analysis and interpretation, and publication of results.
• Establishing a Steering Committee to coordinate and manage the project. The PD(s)/PI(s) will name investigators to serve as members on a Steering Committee and other subcommittees, as appropriate, meeting periodically. Study investigators will be required to accept and implement the common protocol and procedures approved by the Steering Committee.
• Working with the sites/schools to implement the core data collection method and strategy collectively decided upon by the Steering Committee. It is the responsibility of investigators to ensure that data will be submitted by each site/school/participant in a timely way to the study’s data entry system according to the study protocol. Additionally, sites/schools must demonstrate the ability to implement the strategy specifically designed for their individual study population.
• Working with the sites/schools to establish mechanisms for data quality control and monitoring. The recipients are responsible for ensuring accurate and timely assessment of the progress of the study, including the development of procedures to ensure that data collection and management are: (1) adequate for quality control and analysis, (2) as simple as appropriate in order to encourage maximum participation of schools, teachers, administrators, students, and/or parents, as well as avoid unnecessary expense and burden, and (3) sufficiently staffed across the participating sites/schools.

• Establishing procedures, where applicable, for all participating sites/schools, to comply with FDA regulations for studies involving investigational agents or devices and to comply with the requirements of 45 CFR Part 46 for the protection of human subjects, and the NIH policy requirements for the inclusion of women, minorities, and children.
• Cooperating in the reporting of the study findings. NIH will have access to and may periodically review all data generated under an award. Where warranted by appropriate participation, plans for joint publication with NIH of pooled data and conclusions are to be developed by the PD(s)/PI(s) or Steering Committee, as applicable. NIH policies governing possible co-authorship of publications with NIH staff will apply in all cases. In general, to warrant co-authorship, NIH staff must have contributed to the following areas: (a) design of the concepts or experiments being tested; (b) performance of significant portions of the activity; and (c) preparation and authorship of pertinent manuscripts
• Overseeing the overall budget, activities, and performance of the cooperative agreement. Accepting the participatory and cooperative nature of the collaborative research process and complying with policies and practices of NCCIH Sharing data, resources, and software according to the approved sharing policies for NIH.
• Cooperating with NIH staff and contracted on-site monitors in the design and conduct of protocols, analysis of data, and reporting of results of research.
• Agreeing to accept close coordination, cooperation, and management of the project with NIH, including those outlined below under "NIH Responsibilities."
• Agreeing to attend meetings convened by NIH to discuss challenges and lessons learned as well build synergy among the funded trials
• Agreeing to look for opportunities for collaboration and partnership with the funded PIs supported by this RFA and investigators who have received funding for the research networks to explore the science of emotional well-being (https://www.nccih.nih.gov/research/blog/new-research-networks-to-explore-the-science-of-emotional-well-being). Collaboration activities can, for example, include harmonization of measures as appropriate.
• Agreeing to attend and participate in the annual meeting of the emotional research networks.
• Submitting a detailed transition request for the UH3 phase 2months before the end of the UG3 phase, outlining UG3 progress and how negotiated UG3 Milestones have been met, as well as detailed plans, budget, and annual milestones for the UH3 phase. Note that funding of the UG3 phase cooperative agreement does not guarantee support of the UH3 phase.
• Support or other involvement of industry or any other third party in the study e.g., participation by the third party; involvement of study resources or citing the name of the study or NCCIH or other NIH Institute or Center support; or special access to study results, data, findings, or resources -- may be advantageous and appropriate. However, except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification of and concurrence by NIH.
• Any of the above functions may be performed by the recipient organization or by subrecipient organization.
• Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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

• NIH will assign a Project Scientist as the point of contact to work with the PD(s)/PI(s) and participate in 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 awardee and the NIH Project Scientist. With the agreement of the PD(s)/PI(s), the NCCIH Project Scientist or designee may assist in the design, development, and coordination of a common research or clinical protocol and statistical evaluations of data; in the preparation of questionnaires and other data recording forms; and/or in the publication of results.
• NIH will assign a Program Officer who will be responsible for retaining overall programmatic responsibility for the award and will clearly specify to the recipient the name(s) and role(s) of any additional individuals with substantial involvement in the project and the lines of reporting authority.
• NCCIH may designate additional staff to provide advice to the recipient on specific scientific and/or analytic issues. Such staff may include another Project Scientist or Analyst, who will provide direct technical assistance to the recipients to optimize the conduct and/or analysis of the study; or who may assist in the coordination of activities across multiple sites/schools.
• Prior to the start of clinical activities, NIH staff will review and approve study protocols to ensure they are within the scope of peer review and for safety considerations, as required by Federal regulations. NIH will monitor protocol progress and may request that a protocol study be closed to accrual for reasons including (a) accrual rate insufficient to complete the study in a timely fashion; (b) accrual goals met early; (c) poor protocol performance; (d) patient safety and regulatory concerns; (e) study results that are already conclusive; and (f) emergence of new information that diminishes the scientific importance of the study question. NIH will not permit further expenditures of NIH funds for a study after requesting closure (except for patients already on-study).
• NIH will serve as a resource with respect to other ongoing NIH activities that may be relevant to the protocol to facilitate compatibility and avoid unnecessary duplication of effort.
• 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 activities. NCCIH may designate NIH staff or contractors to conduct site initiation, interim, and closeout site visits 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 staff will provide input, expert advice, and suggestions in the design, development, coordination, and implementation of the study objectives.
• NCCIH staff will make recommendations for continued funding based on: a) overall study progress, including sufficient participant and/or data accrual; b) cooperation in carrying out the research (e.g., attendance at Steering Committee meetings, implementation of group decisions, compliance with the terms of award and reporting requirements); and/or c) maintenance of high quality of research, which may allow pooling of data and comparisons across multiple cooperative agreement awards for common data elements.
• NIH staff will conduct an administrative review of the UH3 transition request to determine whether the project will transition to UH3 funding. Criteria for transition to the UH3 phase used in the NIH administrative review include successful achievement of the UG3 milestones, the potential for successfully meeting the UH3 implementation phase plans and milestones, and the availability of funds.
• NIH staff will convene meetings with the investigators of the funded trials to discuss challenges, and lessons learned, and build synergy across the trials and with investigators who have received funding for the research networks to explore the science of emotional well-being (https://www.nccih.nih.gov/research/blog/new-research-networks-to-explore-the-science-of-emotional-well-being).

Areas of Joint Responsibility include:

A Steering Committee organized by the PD(s)/PI(s) will be the main oversight body of the study.

• The Steering Committee has the primary responsibility to design research activities; establish priorities; develop common protocols and manuals, questionnaires, and other data recording forms; establish and maintain quality control among recipients; review progress; monitor patient accrual; coordinate and standardize data management, and cooperate on the publication of results. Major scientific decisions regarding the core data will be determined by the Steering Committee. The Steering Committee will document progress in written reports to the NCCIH Program Officer and will provide periodic supplementary reports upon request.
• The Steering Committee will be composed of the PD(s)/PI(s) and co-investigators as deemed necessary, such as the study biostatistician and trial manager, the NCCIH Project Scientist, and additional designees of NIH. The NCCIH Project Scientist or designee will have voting membership on the Steering Committee, and as appropriate, its subcommittees. The NCCIH Program Officer will serve as an “ex officio” member of the Steering Committee. The Steering Committee will typically meet in-person or via videoconference twice in the first year of the award and then at least yearly thereafter. More frequent phone meetings will occur as required during the award period. The first in-person meeting will occur before clinical activities begin.
• The Steering Committee will ensure that sites and investigators as well as NIH and other research partners fully comply with federal regulatory requirements. This includes, but is not limited to those relating to human subjects' protections, informed consent, and reporting of adverse events.
• The Steering Committee will develop appropriate confidentiality procedures for data collection, processing, storage, and analysis to ensure the confidentiality of data on individual health.
• A DSMP will be required for both phases of the project. An independent DSMB will be appointed and established by NCCIH for the clinical trial, in accordance with NIH and NCCIH policies for monitoring (https://www.nccih.nih.gov/grants/policies/data-and-safety-monitoring-of-nccihfunded-clinical-research)https://nccih.nih.gov/grants/policies/data-safety-monitoringhttps://nccih.nih.gov/grants/policies/data-safety-monitoring).
• The DSMB will play a crucial role in ensuring the safety and welfare of participants enrolled in the trial, will regularly review study progress and some interim data and will provide recommendations to NIH. During the award, the recipient will provide interim data and reporting, as requested, to the Board as outlined in NCCIH guidelines (https://www.nccih.nih.gov/research/guidelines-for-nccih-appointed-data-and-safety-monitoring-boards).
• Organizing and participating in quarterly (or as needed) virtual Steering Committee meetings as well as an annual meeting with the investigators who have received funding for the research networks to explore the science of emotional well-being (https://www.nccih.nih.gov/research/blog/new-research-networks-to-explore-the-science-of-emotional-well-being).

Dispute Resolution:

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

3. Reporting

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

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

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

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

Section VII. Agency Contacts

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

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

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

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

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

Beda Jean-Francois, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 202-313-2144
Email: [email protected]

Elizabeth L. Neilson, PhD, MPH, MSN
Office of Disease Prevention (ODP)
Phone: 301-827-5578
Email: [email protected] 

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

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

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.