The goal of this notice of funding opportunity (NOFO) is to support feasibility trials of complementary and integrative health approaches with physical and/or psychological therapeutic inputs (often called mind and body interventions) for conditions that have been identified by NCCIH as high-priority research topics. This funding opportunity is intended to support feasibility clinical trials that provide new information that are scientifically necessary for the planning and conduct of a subsequent clinical efficacy or effectiveness study, pragmatic trial, or dissemination and implementation trial within NCCIHs mission. NCCIH expects that applications to this NOFO will describe the planned future clinical trial and in so doing demonstrate that the proposed (R34) research is scientifically necessary to design or plan the subsequent competitive full-scale clinical trial. Under this R34, the data collected should be used to fill gaps in scientific knowledge necessary to develop a competitive full-scale clinical trial, including, but not limited to the following: examining feasibility and acceptability of interventions lacking published data; tailoring or adapting the content or structure of an intervention to a specific population, modality, or setting; refining the intervention to determine the most appropriate frequency or duration; determining feasibility of recruitment, retention, and data collection procedures; refining and assessing the feasibility of protocolized multi-component interventions; or examining acceptability and adherence of control conditions. The subsequent full-scale clinical trial should have the potential to make a significant impact on public health. Prior to submitting to this NOFO, applicants are encouraged to contact the appropriate NCCIH Scientific/Research contact person for the science area of the planned application.

PAR-25-274: Feasibility Clinical Trials of Mind and Body Interventions for NCCIH High Priority Research Topics (R34 Clinical Trial Required)

Posted Date: November 21, 2024 Open Date (Earliest Submission Date): January 20, 2025 Expiration Date: November 18, 2026

Updates:

• March 31, 2025: This funding opportunity was updated to align with agency priorities. Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission.
• April 4, 2024: Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025. See Notice NOT-OD-24-084.
• August 31, 2022: Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023. See Notice NOT-OD-22-198.
• August 5, 2022: Implementation Details for the NIH Data Management and Sharing Policy. See Notice NOT-OD-22-189.

Part 1. Overview Information

Participating Organization(s): National Institutes of Health (NIH) Components of Participating Organizations: National Center for Complementary and Integrative Health (NCCIH)

Funding Opportunity Title: Feasibility Clinical Trials of Mind and Body Interventions for NCCIH High Priority Research Topics (R34 Clinical Trial Required) Activity Code: R34 (Planning Grant) Announcement Type: Reissue of PAR-24-084

Funding Opportunity Number (FON): PAR-25-274 Companion Funding Opportunity:

• PAR-24-275, UG3/UH3 Phase 1 Exploratory/Developmental Cooperative Agreement/Exploratory/Developmental Cooperative Agreement Phase II
• PAR-24-276, U24 Resource-Related Research Project (Cooperative Agreements)
• PAR-25-267, R01 Research Project
• PAR-25-268, R01 Research Project

Number of Applications: See Section III. 3. Additional Information on Eligibility. Assistance Listing Number(s): 93.213

Funding Opportunity Purpose: The goal of this notice of funding opportunity (NOFO) is to support feasibility trials of complementary and integrative health approaches with physical and/or psychological therapeutic inputs (often called mind and body interventions) for conditions that have been identified by NCCIH as high-priority research topics. This funding opportunity is intended to support feasibility clinical trials that provide new information that is scientifically necessary for the planning and conduct of a subsequent clinical efficacy or effectiveness study, pragmatic trial, or dissemination and implementation trial within NCCIH’s mission. NCCIH expects that applications to this NOFO will describe the planned future clinical trial and in so doing demonstrate that the proposed (R34) research is scientifically necessary to design or plan the subsequent competitive full-scale clinical trial. Under this R34, the data collected should be used to fill gaps in scientific knowledge necessary to develop a competitive full-scale clinical trial, including, but not limited to the following: examining feasibility and acceptability of interventions lacking published data; tailoring or adapting the content or structure of an intervention to a specific population, modality, or setting; refining the intervention to determine the most appropriate frequency or duration; determining feasibility of recruitment, retention, and data collection procedures; refining and assessing the feasibility of protocolized multi-component interventions; or examining acceptability and adherence of control conditions. The subsequent full-scale clinical trial should have the potential to make a significant impact on public health.

Prior to submitting to this NOFO, applicants are encouraged to contact the appropriate NCCIH Scientific/Research contact person for the science area of the planned application.

Funding Opportunity Goal(s): The National Center for Complementary and Integrative Health (NCCIH) provides funding for research into complementary and integrative health approaches. Research constituting a rigorous evidence base for complementary health approaches will be developed through a range of research strategies including basic and translational research, and clinical investigation.

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.

Due Dates for E.O. 12372: Not Applicable

Required Application Instructions: It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

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

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

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Background

The National Center for Complementary and Integrative Health (NCCIH) is committed to the rigorous investigation of promising complementary and integrative health approaches with physical and/or psychological therapeutic inputs (often called mind and body interventions). These mind and body interventions are widely used by the public, and they are increasingly recognized as a nonpharmacologic approach to symptom management (e.g., chronic pain, mild depression, anxiety). These approaches can be used by individuals to help prevent, treat, or self-manage various conditions, and they can be complementary to conventional health care.

There is a need for research to evaluate mind and body approaches as they are used and delivered to determine whether they are safe and efficacious or effective for given conditions or disorders. For clinical trials to address this need, they must be well designed and test hypotheses that will guide decisions about the inclusion of these interventions or approaches in health care for a given condition or disorder. Investigators need to cite published literature or conduct a series of early-phase clinical trials to gather the multiple types of information to design subsequent large and rigorous efficacy or effectiveness studies. Although the scientific literature may provide the rationale for conducting an efficacy or effectiveness trial, investigators may lack critical information about key elements needed to plan and conduct such a trial. Some key aspects that may need further investigation to plan the future clinical trial could include refining or adapting the intervention to specific populations, modalities, or settings; assessing the feasibility, acceptability, and adherence to protocolized multi-component interventions; and/or finalizing the intervention delivery method, appropriate outcome(s), or recruitment strategy. Feasibility clinical trials can fill these information gaps.

Overview of NCCIH Mind and Body Clinical Trials Research Funding Opportunities: NCCIH has designed a framework for research to describe the broad spectrum of complementary and integrative health research it supports (https://www.nccih.nih.gov/grants/nccih-research-framework). NCCIH supports investigators working on the continuum of the research framework, from basic science, and feasibility research, through high-impact clinical trials as well as research on dissemination and implementation (https://www.nccih.nih.gov/grants/funding/clinicaltrials). We encourage investigators to examine the full suite of available clinical trial notices of funding opportunities (NOFOs) to determine which one best aligns with the proposed stage of intervention development and testing.

NCCIH has an oversight process to provide stewardship and maintain excellence, integrity, and rigor in our supported clinical studies (https://www.nccih.nih.gov/grants/toolbox). Investigators are encouraged to review the NCCIH Clinical Terms of Award for Human Subjects Research (https://www.nccih.nih.gov/research/nccih-clinical-terms-of-award-for-human-subjects-research) to learn more about NCCIH's requirements for clinical research.

Prior to submitting a grant application, NCCIH strongly encourages consulting with NCCIH Scientific/Research extramural program contacts relevant to the area of science for which they are planning to develop an application. Early contact provides an opportunity for NCCIH staff to discuss the scope and goals, and to provide information and guidance.

Research Objectives of the Mind and Body Feasibility Clinical Trial Phase (R34)

The objective of this NOFO is to support the development of building blocks to plan and conduct novel, high priority clinical trials of complementary and integrative health approaches with physical and/or psychological therapeutic inputs (often called mind and body interventions) to enhance the probability of reaching more definitive outcomes in a future clinical trial. Important building blocks that could be supported under this NOFO include refining the experimental protocols, including the assessment protocol, experimental intervention protocol, comparison intervention protocol, and randomization procedures; examining the feasibility of recruiting and retaining participants in the study; and developing supportive materials and resources. Investigators should design the R34 to provide the necessary preliminary data to fill gaps in the literature to justify a future efficacy, effectiveness, pragmatic, or dissemination and implementation trial. Applications should describe and justify the need for feasibility data and ensure that no other published or completed pilot studies have been performed with a similar population and similar intervention. If it is possible to reference successful demonstration of these benchmarks in completed trials or trials currently underway using the proposed or similar intervention and study population, further single-site feasibility work is not needed. Applications proposing such iterative or duplicative studies will be considered of low programmatic relevance, which will decrease likelihood of funding.

The following are examples of the types of aims appropriate for feasibility clinical trials proposed under this NOFO:

• Assessment of acceptability and adherence to dose, frequency, and/or duration of the intervention.
• Substantial intervention refinement to tailor, adapt, or customize an intervention to a new population, modality, or setting. The need for adaptation/tailoring should be based upon a strong scientific rationale for the proposed adaptation. Comparisons on feasibility outcomes between the adapted intervention to the original intervention are strongly encouraged.
• Development and assessment of acceptability or adherence to a protocolized multi-component intervention.
• Iterative intervention refinement via several small cohorts to address challenges with intervention fidelity, participant adherence, or selection of appropriate outcomes.
• Assessment of feasibility to measure outcomes within designated time frames; train interventionists to deliver the intervention with fidelity; and/or recruit, randomize, and retain participants in the intervention or comparison condition.
• Development and feasibility testing of the strategies for integrating a mind and body approach into a health care system or delivery, to inform design of future pragmatic or implementation science trials.
• Assessment of acceptability or feasibility of randomization or other aspects of trial design.
• Development and feasibility testing of an appropriate control/comparison intervention for a future larger study.
• Demonstration of feasibility of an intervention to be delivered remotely (e.g., tailoring of an algorithm for use in an mHealth intervention or smartphone application).

Design Considerations: Investigators should propose a randomized controlled trial design with at least one intervention arm and one comparator arm. There should be strong rationale for the comparator condition (e.g., time and attention control, usual care, standard of care, sham condition, and/or active comparator(s)) based on the research question you plan to address in the future powered trial. Due to lack of rigor and potential expectancy effects, NCCIH will not support studies proposing a waitlist comparator condition.

Power Recommendations: Pilot or feasibility studies are carried out in preparation for future large-scale, adequately powered studies and, therefore, should address key feasibility issues such as participant recruitment and retention; burden and adherence to the intervention; provider fidelity to the intervention; and data collection methods. Given the limited sample sizes that can be supported under this R34 grant mechanism, proposing to conduct fully powered tests of clinical outcomes (i.e., efficacy) or underpowered tests of outcomes (i.e., "preliminary efficacy") or attempting to utilize the highly variable point estimate of an effect size for power calculations would be non-responsive as noted below.

As pilot and feasibility studies are not designed (or powered) to address efficacy or effectiveness of an approach or intervention, statistical methods should be mainly descriptive. Applicants should define feasibility/acceptability with quantitative benchmarks corresponding to each assessment category. Scientific and/or statistical justification should be provided to demonstrate how the sample size is sufficient to make a feasibility/acceptability determination in accordance with benchmarks. Sample sizes used in pilot studies are not powered for testing pre-specified hypotheses as expected for confirmatory studies. Sample sizes for subsequent fully powered studies should be based on determining a clinically meaningful improvement due to the intervention in the appropriate research population. Investigators should consult the NCCIH website (https://www.nccih.nih.gov/grants/pilot-studies-common-uses-and-misuses) for more information on the uses and misuses of feasibility studies.

Group-Based Interventions: In some cases, investigators who wish to evaluate the effect of an intervention on a health-related biomedical or behavioral outcome may propose a study in which (1) groups or clusters are assigned to study arms and individual observations are analyzed to evaluate the effect of the intervention, or (2) participants are assigned individually to study arms but receive at least some of their intervention in a real or virtual group or through a shared facilitator. Investigators should provide a strong rationale for the choice among trial design options. The selection of study design should be guided by decisions about how best to deliver the intervention and by concerns regarding contamination and logistics. Applicants should show that their methods are appropriate given their plans for assignment of participants and delivery of interventions. Additional information is available at https://researchmethodsresources.nih.gov/.

Mechanistic Measures: There are often questions about whether feasibility trials should include mechanistic aims to evaluate how interventions work. Trials submitted under this NOFO should not include aims to assess the impact/efficacy of an intervention on a mechanism of action or evaluate mediation effects. Mechanistic measures may be included in feasibility trials for the purpose of determining if collecting the mechanistic measure is feasible, which can inform whether mediation or moderation aims should be included in a future, large-scale efficacy or effectiveness trial. Applications would need to justify why the mechanistic outcome(s) should be included in the future efficacy or effectiveness trial. The inclusion of mechanistic measures should not introduce significant burden for participants or utilize a significant portion of the budget. NCCIH has other funding mechanisms to support basic, mechanistic and translational research (NOT-AT-21-006).

Preliminary Data Requirements

Preliminary data are not required for this NOFO unless the application involves a natural product (i.e. botanicals, probiotics, and products marketed as dietary supplements) as part of a multi-component intervention. However, there should be a clear and compelling scientific rationale for the need for a feasibility study or intervention adaptation.

For applications studying the feasibility or acceptability of including a natural product as part of a multi-component intervention, the application must provide published data that the formulation of the proposed natural product has demonstrated efficacy for the condition being studied from at least one fully powered placebo-controlled trial. Trials including natural products will have to adhere to the NCCIH Policy on Natural Product Integrity (http://NCCIH.nih.gov/research/policies/naturalproduct.htm).

Timeline

Investigators should propose a realistic timeline for the startup and completion of the clinical trial and provide contingency plans to proactively confront potential delays or disturbances to the planned trial.

NCCIH Priorities for Clinical Trials of Mind and Body Interventions

NCCIH has identified targeted areas of investigation to align with the NCCIH Strategic Plan (https://www.nccih.nih.gov/about/strategic-plans-and-reports). For this funding opportunity, applications will be considered high programmatic priority if they address one of following criteria related to the intervention of study:

• The complementary or integrative approaches with physical and/or psychological therapeutic inputs (often called mind and body interventions) should include one or more of the following:
  • Physical approaches such as spinal manipulation or mobilization, massage, tai chi, qi gong, yoga, acupuncture; or
  • Psychological approaches such as hypnosis, guided imagery, breathing exercises, progressive relaxation, meditation, biofeedback, mindfulness techniques, music or other art-based therapies
  • Multi-component interventions such as naturopathic medicine, traditional Chinese medicine, Ayurvedic medicine, chiropractic care, or a combination of two or more of the specific complementary health approaches (e.g., massage and biofeedback, or natural product and mindfulness); or integrated approaches to care in which a complementary health approach is used in combination with standard care (e.g., mindfulness or yoga as augmentation to conventional medications); or
  • Multilevel intervention level (patient, caregivers of patient, clinicians, and health care system) where at least one level of intervention includes a mind and body intervention.

In addition, proposed projects could include an outcome measure(s) that relates to at least one of the following high-priority topic areas:

• Promotion of health behaviors, health restoration, emotional well-being, or resilience;
• Prevention or treatment of symptoms such as sleep disorders or disturbances, depression, anxiety, chronic stress, post-traumatic stress (disorder), obesity, and acute and chronic pain conditions;
• Whole person health outcomes including multisystem or multilevel outcomes;
• Minority health and reduction of disparities in areas such as pain, obesity, mental and emotional behavioral health, and maternal health;
• Social and structural determinants of health (https://www.ninr.nih.gov/researchandfunding/nih-sdohrcc);
• Enhancement of adherence to medications or prescribed behavioral approaches (e.g., physical activity and healthy eating);
• Reduction or deprescribing of inappropriate use of medications or other substances (e.g., drugs of abuse or medications that are contraindicated in specific patient populations); or
• Reduction in risk for/incidence of HIV, or comorbidities, coinfections and complications from HIV (https://abs2.od.nih.gov/Docs/NIH_StrategicPlan_FY2021-2025.pdf)

When evidence justifies, NCCIH encourages applications to conduct studies in a way that assesses the impact of integrating interventions into relevant settings (e.g., health care systems, schools, Federally Qualified Health Centers, military or Veteran health care delivery organizations, community organizations, justice systems, or homeless shelters).

All National Institutes of Health (NIH)-funded research must adhere to the Code of Federal Regulations, which outlines specific requirements to enhance protections for pregnant women, human fetuses, and neonates; children; and prisoners (https://grants.nih.gov/policy/humansubjects/policies-and-regulations/vulnerable-populations.htm). The Inclusion Across the Lifespan policy requires that individuals of all ages, including children (i.e. individuals under the age of 18) and older adults, must be included in all human subjects research, conducted or supported by NIH, unless there are scientific or ethical reasons not to include them (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-18-116.html).

Applications proposing research topics not identified above as high programmatic priority can be submitted but may be considered lower programmatic priority, which may reduce the likelihood of funding. Applications proposing research studies using an intervention and patient population that are the same as or very similar to those used in studies already in progress, conducted, or published by other groups are likely to be lower programmatic priority.

Clinical Trials Not Responsive to this NOFO: The following types of clinical trials are not responsive to this NOFO, and applications proposing such activities will be deemed non-responsive and not reviewed:

• Studies proposing to analyze data from a feasibility trial to assess efficacy/effectiveness of an intervention or estimate effect size (https://www.nccih.nih.gov/grants/pilot-studies-common-uses-and-misuses).
• Trials that do not include an aim to assess the feasibility, acceptability, fidelity, and/or adherence to the intervention.
• Studies that do not include a mind and body intervention.
• Studies that propose a waitlist control.
• Trials that propose to assess feasibility of interventions for the treatment or prevention of cancer. (Investigators interested in cancer treatment or prevention trials should contact the National Cancer Institute.)

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

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

Section II. Award Information

Funding Instrument: Grant: A financial assistance mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed:

• New
• Resubmission

The OER Glossary and the How to Apply Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO.

Clinical Trial? Required: Only accepting applications that propose clinical trial(s). Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards: The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Award Budget: This R34 is limited to direct costs requests of up to $450,000 over the entire project period. Although variations from year to year are permissible, in no case may any year be more than $225,000 in direct costs.

Award Project Period: The maximum project period is 3 years.

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations:

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

Foreign Organizations:

• Non-domestic (non-U.S.) Entities (Foreign Organizations) are not eligible to apply.
• Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
• Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Required Registrations:

Applicant Organizations: Applicant organizations must complete and maintain the following registrations as described in the How to Apply- Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information.

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

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

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support. For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply-Application Guide.

2. Cost Sharing

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

3. Additional Information on Eligibility

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

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

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

Applications with Foreign components are encouraged to read NCCIH International Health Research page. Foreign components can include foreign collaborators or consultants, but should not include foreign sites outside of the U.S. or Canada, according to NCCIH’s policy.

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

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

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

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

• SF424(R&R) Cover: All instructions in the How to Apply - Application Guide must be followed.
• SF424(R&R) Project/Performance Site Locations: All instructions in the How to Apply- Application Guide must be followed.
• SF424(R&R) Other Project Information: All instructions in the How to Apply- Application Guide must be followed.
• SF424(R&R) Senior/Key Person Profile: All instructions in the How to Apply- Application Guide must be followed.
  • We strongly encourage that all clinical trials include a biostatistician as part of the key personnel, and the application should reflect their hands-on involvement in the design and implementation of the study protocol.
• R&R or Modular Budget: All instructions in the How to Apply- Application Guide must be followed.
  • All instructions in the SF424 (R&R) Application Guide must be followed.
  • The budget for the first year of the grant should reflect the support needed for trial startup.
  • If parts of the costs of the trial are to be provided by sources other than NIH, these contributions must be presented in detail in the budget justification. Include budget support for the publication and dissemination of findings. Applicants should budget for the services of appropriate safety monitoring (e.g., Medical Safety Monitor, Independent Medical Monitor, or Safety Monitoring Committee), as indicated; https://www.nccih.nih.gov/grants/policies/data-and-safety-monitoring-of-nccihfunded-clinical-research.
• R&R Subaward Budget: All instructions in the How to Apply-Application Guide must be followed.
• PHS 398 Cover Page Supplement: All instructions in the How to Apply- Application Guide must be followed.
• PHS 398 Research Plan: All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions:
  • Research Strategy: The research strategy should be organized in a manner that will facilitate peer review. The body of the application should present a concise overview of the state of the science; current status and relevance of the trial; a discussion of the specific protocol; and the approach to data collection, analysis, and dissemination. The following criteria should be addressed:
    • Importance of Research: The significance and innovation of the proposed clinical trial and importance of the question must be clearly stated. It is particularly important that there be a discussion of how the trial will test the proposed hypotheses and how or why there is clinical equipoise. The application should make clear the need for and timeliness of the study, with emphasis on how the results will address an evidence gap and therefore advance our knowledge of theory and practice in this area. A discussion of the costs and benefits of the study should be included for evaluation of the trial’s significance. The importance of the proposed feasibility trial and why it is scientifically necessary to plan the subsequent future trial should be described. Discuss how the proposed trial will test the feasibility hypotheses and how the results of the trial (positive or negative) will guide decisions about whether a subsequent study is feasible, and/or evidence that additional studies must be completed before proceeding to a full-scale trial. Applications should address the reasons for selection of the intervention. This may include public health impact if subsequent efficacy trials are conducted and positive, ethical dimensions, and patient perspectives on acceptability of the proposed intervention. Characteristics of any preliminary research results provided in support of the proposed project, whether conducted by the applicant or others, should be described in the application so that peer reviewers may evaluate the strength of the supporting evidence. The applicant should also discuss the limitations of those data. Explain how the application challenges and seeks to shift current research or clinical practice paradigms or guidelines.
    • Rigor and Feasibility: The research approach section should include a description of the supporting data and the experimental approach.
      • Supporting Data: Justification for the study may be presented as results from previous clinical studies conducted by the investigative team or from the scientific literature. Study conceptualization and planning must be at a stage sufficient to allow for an assessment of the likelihood of trial success.
      • Experimental Approach: A summary of the proposed feasibility trial protocol should be presented in the Research Strategy and should include the items listed below.
        • A description of why the target population is an appropriate group to address the proposed hypotheses and how or if results will generalize to a broader population.
        • A description of the mind and body or multi-component intervention to be tested, including elements of the intervention, proposed methods of assessing fidelity of intervention delivery and intervention performance, time duration of delivery (for clinician provided interventions) or participant practice (in group or individual/home settings), and frequency of delivery or practice.
        • A description of the required training and/or licensure/credentialing of individuals providing the intervention across proposed site(s) if necessary.
        • A description and justification for assessments, including clinical, laboratory, physiological, behavioral, patient-centered, or other outcomes. Use of patient-reported outcomes, including those available through the Patient-Reported Outcomes Measurement Information System (PROMIS), NIH Toolbox, and Quality of Life in Neurological Disorders (NeuroQoL), as well as nontraditional data collection approaches (e.g., telephone, mobile devices, or web-based systems) need to be described. A description of the laboratory evaluations (as appropriate) and plans to implement and monitor Good Clinical Practices (GCP), Good Laboratory Practices (GLP), and Good Manufacturing Practices (GMP), as appropriate, should be provided.
        • Investigators should utilize instruments validated in multiple languages representing the complexity of their participant population.
        • Discussion of potential challenges expected in implementing the trial and how these might be overcome.
        • A timeline, which could be provided as a table or graph, for reaching important study milestones such as: (a) obtaining regulatory approval of the final protocol; (b) establishing agreements with participating partners, if relevant; (c) finalizing the study procedures and training participating clinical site staff; and (d) starting enrollment and completing all subject follow-up and data collection activities.
        • Future clinical trial: a concise summary of the subsequent proposed fully powered trial should be provided, including the study design (efficacy, effectiveness, or pragmatic) and how the proposed feasibility study will inform the design of that trial. Provide clear evidence of equipoise about the future trial.
        • Investigators should check https://reporter.nih.gov/ and https://clinicaltrials.gov/ to provide justification that the work proposed is not duplicative of completed or ongoing trials. Applicants should not propose work that duplicates other feasibility studies already funded or other trials that are underway using a similar intervention in a similar population.
        • For applications that propose the use of an app or clinical decision support software, applicants must consult with their Institutional Review Board (IRB) to determine whether the approach may qualify as a medical device. If so, or if in doubt, applicants should contact the U.S. Food and Drug Administration (FDA) prior to applying to determine whether an IDE application is necessary for the proposed clinical research (https://www.fda.gov/medical-devices/software-medical-device-samd/your-clinical-decision-support-software-it-medical-device).
  • Letters of Support:
    • Letters of support from clinicians or clinical department chairs whose support are necessary to the successful conduct of the trial should be provided. Applicants are also encouraged to include documentation of the commitment of any subcontractors and consultants, as well as service agreements for personnel or facilities. Letters of commitment must be co-signed by the business official of the collaborating center.
    • In addition, if utilizing a natural product as part of a multi-component intervention, a letter of support should document that sufficient supply of the natural product will be available for testing at the time of award, including expiration date; the supplier will meet CMC specifications; and the supplier will provide the data necessary for the investigator to adhere to NIH policies and FDA regulations. Documentation should include a letter of agreement from the third party supplying the natural product.
    • If parts of the costs of the trial are to be provided by sources other than NCCIH, provide letter(s) of support signed by an authorized representative.
  • Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply- Application Guide.
  • Other Plan(s):
    • All instructions in the How to Apply-Application Guide must be followed, with the following additional instructions:
    • All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.
  • Appendix:
    • Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply- Application Guide.
    • No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.
• PHS Human Subjects and Clinical Trials Information: When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply- Application Guide, with the following additional instructions:
  • If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.
  • Study Record: PHS Human Subjects and Clinical Trials Information:
    • All instructions in the How to Apply- Application Guide must be followed.
    • Section 2 - Study Population Characteristics:
      • 2.5 Recruitment and Retention Plan: Describe the following: 1) the planned recruitment methods, including use of contact lists, 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. Investigators are encouraged to review the NCCIH Study Accrual and Retention Plan (https://www.nccih.nih.gov/grants/policies/nccih-policy-study-accrual-and-retention-for-human-subject-research). Applicants must provide strong evidence of the availability of appropriate institutional resources and suitable patient populations. Documentation of the availability of eligible participants must be provided. The application must provide relevant information that addresses the feasibility of recruiting a robust sample of eligible participants.
    • 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, NCCIH requires independent monitoring for research involving human subjects. Applicants should refer to NIH’s policy on data and safety monitoring (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html), as well as the NCCIH Guidelines for Data and Safety Monitoring (https://www.nccih.nih.gov/grants/policies/data-and-safety-monitoring-of-nccihfunded-clinical-research). The data and safety monitoring plan must explicitly describe plans to monitor participant safety with appropriate safeguards to minimize risk. The Independent Monitoring Committee (IMC) or Data and Safety Monitoring Board (DSMB) will have the responsibility to review interim and final data and to recommend whether the protocol should be modified, and, at each meeting, whether the study should be continued or terminated early. Thus, its ethical responsibilities, to the participants as well as to the integrity of the study, are of paramount importance to NCCIH. The IMC/DSMB will meet in person or by phone at least twice a year. To avoid conflicts of interest in peer review, applicants should not appoint IMC/DSMB members in advance of the peer review, or even inquire about the interest of possible DSMB members.
    • Section 4 - Protocol Synopsis:
      • 4.5. Will the study use an FDA-regulated intervention?
        • 4.5.a. If yes, describe the availability of Investigational Product (IP) and Investigational New Drug (IND)/Investigational Device Exemption (IDE) status: If the proposed clinical trial will use a device, natural product (such as botanicals, probiotics, and products marketed as dietary supplementsl), or drug, this attachment should describe correspondence from the FDA indicating whether the proposed study will require an IND/IDE. Investigators should describe the process that will be used for attaining all necessary FDA or other applicable regulatory agency approvals necessary to the conduct of the trial and associated timeline. For trials using an FDA-regulated product that requires an IND/IDE application, the grant application must include evidence regarding the outcome of a pre-IND meeting, or other evidence of communication with FDA. If the protocol is conducted under a non-U.S. regulatory agency, the applicant should submit a plan for attaining those regulatory approvals. If the protocol is exempt from an IND/IDE, a copy of the exemption letter from the FDA should be provided as part of the PDF file attachment. The FDA has provided guidance indicating that when substances that are Generally Recognized as Safe (GRAS) are used in a clinical trial to evaluate the product’s ability to diagnose, cure, mitigate, treat, or prevent disease it may require an IND under part 312 (https://www.fda.gov/media/79386/download). If an IND is required by the FDA for the proposed trial, the IND must be submitted to the FDA with no clinical hold imposed by the FDA prior to the application being funded.
  • Delayed Onset Study: Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the How to Apply- Application Guide must be followed.
• PHS Assignment Request Form: All instructions in the How to Apply- Application Guide must be followed.

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

See Part 2. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov.

4. Submission Dates and Times

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

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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

Information on the submission process and a definition of on-time submission are provided in the How to Apply-Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

Pre-award costs are allowable only as described in the NIH Grants Policy Statement Section 7.9.1 Selected Items of Cost.

For trials using an FDA-regulated product and requiring an IND application, the applicant must either hold or be able to reference an open IND for the trial, or the applicant must obtain an IND with no clinical hold from the FDA prior to any award. The details of the IND status of the product should be provided in the attachment included in the study record for section 4.5. If the FDA has granted a waiver for either trial proposed in the application, then the applicant can provide this letter as part of the response to item 4.5 in the study record. If the protocol is conducted under a non-U.S. regulatory agency, then equivalent determinations and documentation must be provided to NCCIH prior to a grant award. Funding will not be made until the necessary regulatory approvals are in place for the conduct of the proposed clinical trial. If the product to be studied is on the Drug Enforcement Agency (DEA) controlled substance list, the applicant must describe the DEA license and registrations necessary to complete the proposed trial. Again, no awards will be made until all necessary DEA licenses and registrations are in place.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the How to Apply - Application Guide. Paper applications will not be accepted.

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

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

Important reminders:

• All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form.
• Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this NOFO for information on registration requirements.
• The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply - Application Guide.
• See more tips for avoiding common errors.

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 NOFO number and title, PD/PI name, and title of the application.

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

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

Post Submission Materials: Applicants are required to follow the instructions for post-submission materials, as described in the policy. In addition to the post-submission materials allowed by NIH policy in NOT-OD-19-083, the following post-submission materials are allowed:

• Updates to section 4.5 on communications with the FDA in regard to IND/IDE requirements

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.

Overall Impact: 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 scored review criteria and additional review criteria (as applicable for the project proposed). An application does not need to be strong in all categories to be judged likely to have a major scientific impact.

Scored Review Criteria: Reviewers will consider Factors 1, 2 and 3 in the determination of scientific merit, and in providing an overall impact score. In addition, Factors 1 and 2 will each receive a separate factor score.

• Factor 1. Importance of the Research (Significance and Innovation)

  • Significance: Evaluate the importance of the proposed research in the context of current scientific challenges and opportunities, either for advancing knowledge within the field, or more broadly. Assess whether the application addresses an important gap in knowledge in the field, would solve a critical problem, or create a valuable conceptual or technical advance. Evaluate the rationale for undertaking the study, the rigor of the scientific background for the work (e.g., prior literature and/or preliminary data) and whether the scientific background justifies the proposed study.
  • Innovation: Evaluate the extent to which innovation influences the importance of undertaking the proposed research. Note that while technical or conceptual innovation can influence the importance of the proposed research, a project that is not applying novel concepts or approaches may be of critical importance for the field. Evaluate whether the proposed work applies novel concepts, methods or technologies or uses existing concepts, methods, technologies in novel ways, to enhance the overall impact of the project.
  • Specific to this NOFO:
    • Evaluate whether performing the future larger clinical study is important in the context of the present knowledge on clinical mind and body research.
    • Evaluate whether the proposed feasibility trial is scientifically necessary to inform the design and conduct of a subsequent trial.

• Factor 2. Rigor and Feasibility (Approach)

  • Approach: Evaluate the scientific quality of the proposed work. Evaluate the likelihood that compelling, reproducible findings will result (rigor) and assess whether the proposed studies can be done well and within the timeframes proposed (feasibility).
    • Rigor: Evaluate the potential to produce unbiased, reproducible, robust data. Evaluate the rigor of experimental design and whether appropriate controls are in place. Evaluate whether the sample size is sufficient and well-justified. Assess the quality of the plans for analysis, interpretation, and reporting of results. Evaluate whether the investigators presented adequate plans to address relevant biological variables, such as sex or age, in the design, analysis, and reporting. For applications involving human subjects or vertebrate animals, also evaluate:
      • the rigor of the intervention or study manipulation (if applicable to the study design).
      • whether outcome variables are justified.
      • whether the results will be generalizable or, in the case of a rare disease/special group, relevant to the particular subgroup.
      • whether the sample is appropriate and sufficiently diverse to address the proposed question(s). For applications involving human subjects, including clinical trials, assess the adequacy of inclusion plans as appropriate for the scientific goals of the research. Considerations of appropriateness may include disease/condition/behavior incidence, prevalence, or population burden, population representation, and/or current state of the science.
    • Feasibility: Evaluate whether the proposed approach is sound and achievable, including plans to address problems or new challenges that emerge in the work. For proposed studies in which feasibility may be less certain, evaluate whether the uncertainty is balanced by the potential for major advances. For applications involving human subjects, including clinical trials, evaluate the adequacy and feasibility of the plan to recruit and retain a study population that appropriately models the target population. Additionally, evaluate the likelihood of successfully achieving the proposed enrollment based on age, race, ethnicity, and sex. For clinical trial applications, evaluate whether the study timeline and milestones are feasible.
  • Specific to this NOFO:
    • Evaluate how the proposed study relates to a larger strategy for research and development of the intervention, and how the proposed study provides pilot and feasibility data needed to advance that strategy.
    • Evaluate the strength of the evidence for equipoise for the future trial.
    • Evaluate whether the mind and body intervention has been appropriately characterized, including specific elements of the intervention, the proposed methods of assessing fidelity of intervention delivery and intervention performance, time duration of delivery (for clinician provided interventions) or participant practice (in group or individual/home settings), and frequency of delivery or practice.
    • Evaluate if the application adequately addresses the appropriate regulatory requirements (IND, IDE, DEA) and the required training and/or licensure/credentialing of individuals providing the intervention across the proposed site(s), if necessary.

• Factor 3. Expertise and Resources (Investigator(s) and Environment)

  • Investigator(s): Evaluate whether the investigator(s) have demonstrated background, training, and expertise, as appropriate for their career stage, to conduct the proposed work. For Multiple Principal Investigator (MPI) applications, assess the quality of the leadership plan to facilitate coordination and collaboration.
  • Environment: Evaluate whether the institutional resources are appropriate to ensure the successful execution of the proposed work.
  • Specific to this NOFO:
    • Evaluate the documentation of the availability of the requisite eligible subject pool at the proposed clinical trial site(s) and the documentation of the commitment of any subcontractors and consultants, as well as service agreements for personnel and facilities.

Additional Review Criteria: As applicable for the project proposed, reviewers will consider the following additional items while determining scientific and technical merit, but will not give criterion scores for these items, and should consider them in providing an overall impact score.

• Protections for Human Subjects: For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, 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, 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.
• Vertebrate Animals: When the proposed research includes Vertebrate Animals, evaluate the involvement of live vertebrate animals 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. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animals Section.
• Biohazards: When the proposed research includes Biohazards, evaluate whether specific materials or procedures that will be used are significantly hazardous to research personnel and/or the environment, and whether adequate protection is proposed.
• Resubmissions: As applicable, evaluate the full application as now presented.
• Renewals: As applicable, evaluate the progress made in the last funding period.
• Revisions: Not applicable.

Additional Review Considerations: 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.

• Authentication of Key Biological and/or Chemical Resources: For projects involving key biological and/or chemical resources, evaluate the brief plans proposed for identifying and ensuring the validity of those resources.
• Budget and Period of Support: Evaluate 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.

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

• 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.

Please note that reviewers will not consider race, ethnicity, age, or sex of a researcher, award participant, or trainee, even in part, in providing critiques, scores, or funding recommendations. NIH will not consider such factors in making its funding decisions.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant’s federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov. NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant’s integrity, business ethics, and performance record of managing Federal awards per 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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

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

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

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

• ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm
• Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.
• Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of the participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).
• Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

2. Administrative and National Policy Requirements

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

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities.
• If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by the HHS Office for Civil Rights website.
• HHS recognizes that NIH research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this NOFO.
• All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.
• Recipients are responsible for ensuring that their activities comply with all applicable federal regulations. NIH may terminate awards under certain circumstances. See 2 CFR Part 200.340 Termination and NIH Grants Policy Statement Section 8.5.2 Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding of Support.

Successful recipients under this NOFO agree that:

• Where the award funding involves implementing, acquiring, or upgrading health IT for activities by any funded entity, recipients and subrecipient(s) are required to: Use health IT that meets standards and implementation specifications adopted in 45 CFR part 170, Subpart B, if such standards and implementation specifications can support the activity. Visit https://www.ecfr.gov/current/title-45/subtitle-A/subchapter-D/part-170/subpart-B to learn more.
• Where the award funding involves implementing, acquiring, or upgrading health IT for activities by eligible clinicians in ambulatory settings, or hospitals, eligible under Sections 4101, 4102, and 4201 of the HITECH Act, use health IT certified under the ONC Health IT Certification Program if certified technology can support the activity. Visit https://www.healthit.gov/topic/certification-ehrs/certification-health-it to learn more.
• Pursuant to the Cybersecurity Act of 2015, Div. N, § 405, Pub. Law 114-113, 6 USC § 1533(d), the HHS Secretary has established a common set of voluntary, consensus-based, and industry-led guidelines, best practices, methodologies, procedures, and processes.

Successful recipients under this NOFO agree that: When recipients, subrecipients, or third-party entities have: * ongoing and consistent access to HHS owned or operated information or operational technology systems; and * receive, maintain, transmit, store, access, exchange, process, or utilize personal identifiable information (PII) or personal health information (PHI) obtained from the awarding HHS agency for the purposes of executing the award. Recipients shall develop plans and procedures, modeled after the NIST Cybersecurity framework, to protect HHS systems and data. Please refer to NIH Post-Award Monitoring and Reporting for additional information.

Cooperative Agreement Terms and Conditions of Award: Not Applicable

3. Data Management and Sharing

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

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

Section VII. Agency Contacts

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

Application Submission Contacts:

• eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)
  • Finding Help Online: https://www.era.nih.gov/need-help (preferred method of contact)
  • Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
• General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
  • Email: [email protected] (preferred method of contact)
  • Telephone: 301-480-7075
• Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
  • Contact Center Telephone: 800-518-4726
  • Email: [email protected]

Scientific/Research Contact(s):

• Jennifer N. Baumgartner, Ph.D. National Center for Complementary and Integrative Health (NCCIH) Phone: 301-402-4084 Email: [email protected]

Peer Review Contact(s):

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

Financial/Grants Management Contact(s):

• 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.

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

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