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 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.

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



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

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Background 

The 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. To move through the clinical trial process, investigators need to rely on and 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; finalizing the intervention delivery method, and determining appropriate outcome(s), or recruitment strategies. Early phase clinical trials supported under this notice of funding opportunity (NOFO) can fill this information gap, thereby improving study design and feasibility. That is, multi-site feasibility trials can provide valuable information regarding whether the intervention can be delivered with fidelity by multiple providers across multiple sites; determine feasibility of recruitment, randomization, and retention strategies; and test methods for consistent data collection including follow-up data to minimize missing data.  

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 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.   

Prior to submitting an application, NCCIH strongly encourages consultation with the NCCIH Scientific/Research 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 Multi-Site Feasibility Clinical Trial (R01) 

This NOFO invites applications for investigator-initiated clinical trials of complementary and integrative health approaches with physical and/or psychological therapeutic inputs (often called mind and body interventions) in NCCIH-designated areas of high research priority. Applications submitted under this NOFO are expected to propose a multi-site feasibility clinical trial that will facilitate the design and execution of a future fully powered multi-site clinical trial (see examples below). To justify the need for a multi-site feasibility clinical trial, applicants must provide their own preliminary data or cite extant published data from a single site feasibility trial (see preliminary data requirements below). If previous multi-site feasibility trials have been published, are completed, or underway, then further feasibility research is not needed. Applications proposing such iterative or duplicative studies will be considered of low programmatic relevance. The application should address any remaining gaps in knowledge that are needed before conducting a fully powered, multi-site efficacy, effectiveness, pragmatic trial, or dissemination and implementation trial. 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.  

For this NOFO, multi-site feasibility clinical trials are defined as trials that enroll research participants from at least two sites that are geographically distinct and nonoverlapping with respect to the population of patients engaging with services and are likely to recruit diverse participants. Demonstrating the ability to deliver an intervention with fidelity across sites is critical to demonstrating the ability to perform a fully powered multi-site efficacy or effectiveness clinical trial. Multiple sites are necessary in efficacy and effectiveness trials to increase the generalizability of the findings, by increasing the size and diversity of eligible participants to enhance recruitment efforts. 

Appropriate goals for multi-site feasibility clinical trials proposed in response to this NOFO include but are not limited to:

• Demonstrate feasibility of recruitment rate, randomization, and retention of participants across multiple sites.  
• Assess whether the intervention can be delivered with fidelity across sites, and/or assess whether minor intervention adaptation is useful to enhance adherence, outcome selection, and/or fidelity. 
• Demonstrate acceptability and/or adherence to a protocolized multi-component intervention across sites. 
• Demonstrate feasibility in measuring outcomes within designated time frames, training interventionists, and delivering the intervention with fidelity across sites. 
• Demonstrate participant adherence to the intervention throughout the study across sites. 
• Demonstrate consistent collection of clinical data including follow-up data across sites. 
• Assess feasibility of strategies for integrating a mind and body approach into multiple health care systems to inform the execution of future pragmatic or implementation research trials. 
• Determine appropriate control/comparison condition for future large-scale study. 

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 issues of process (e.g., recruitment, retention, feasibility, adherence, and/or fidelity) and/or outcomes assessment (e.g., feasibility of the method, frequency, burden, and duration of data collection procedures). Given the limited sample sizes that can be supported under this R01 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 future power calculations would not be appropriate and are noted as nonresponsive 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 use quantitative benchmarks corresponding to each assessment category in determining trial feasibility. 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 proposed benchmarks. Sample sizes used in pilot studies are not formally powered for testing prespecified hypotheses as conventionally expected for confirmatory studies. Sample sizes for subsequent fully powered studies should be based on an achievable, clinically meaningful improvement due to the intervention in the research population with appropriate power calculations. 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 multi-site 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 About the Intervention: 

This NOFO is appropriate when there is a clear and compelling rationale, a rigorous empirical basis, and a scientific premise to conduct a multi-site feasibility trial. The following preliminary data from previous studies (preferred from published literature, or the team’s previous research) on a similar intervention, patient population and age group as proposed in the current application are required:

• Demonstration that an intervention similar to the one proposed in the trial is well tolerated (does not produce frequent severe adverse events) in pilot human studies.
• Pilot single-site feasibility data on a similar intervention in a clinical population similar to the one that will be studied in the proposed trial (e.g., a proposed study to examine vinyasa yoga in adults with anxiety may cite pilot work on hatha yoga in a population of adults with depression and anxiety)
• Demonstrated adherence (e.g., cite a pilot study of similar duration with sufficient adherence).
• Demonstrated retention of participants for a similar study duration (e.g., cite a pilot study that retained a sufficient percentage of participants at the primary outcome time point).
• Information to justify how the intervention is delivered (e.g., duration of individual intervention, frequency of delivery, and timeline of intervention delivery to achieve clinical benefit) in the study. For example, the intervention could be delivered as a single 30-minute session once a week for 8 weeks, or as self-paced 5-minute modules over 10 weeks. Preliminary data should demonstrate that the selected doses are feasible and likely to have the greatest impact on clinical outcome and minimize the risk of adverse events.

Preliminary Data about the Research Team:

In addition, all the following information demonstrating the research team’s collective experience conducting clinical trials is required:

• Delivered a similar intervention via the same delivery mode in a clinical trial with fidelity.
• Successfully recruited, randomized, and retained similar participants.
• Successfully randomized participants to similar intervention and control conditions.
• Achieved adherence to a similar intervention study protocol by research staff.
• Retained participants for a similar study duration.
• Completed collection of follow-up data with consistency and minimal missing data.
• Published results from previous completed trials. 

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 natural product proposed has demonstrated efficacy for the condition being studied from at least one fully powered placebo-controlled trial.

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 a 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 disparities¹ 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 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 of lesser or lower programmatic priority, could 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 as well.

¹ NIH-designated health disparity populations include racial and ethnic minorities (African Americans/Blacks, Hispanics/Latinos, American Indians/Alaska Natives, Asian Americans, Native Hawaiians, and Other Pacific Islanders), sexual and gender minorities, socioeconomically disadvantaged populations, under-served rural populations, and people with disabilities.

Types of Clinical Trials Not Responsive to this NOFO:

Applications proposing the following activities will be deemed nonresponsive:

• Studies proposing to analyze data from a feasibility trial to assess efficacy/effectiveness of an intervention or estimate effect size (Pilot Studies: Common Uses and Misuses).
• Trials that do not include an aim to assess the multi-site feasibility, acceptability, fidelity, and/or adherence to the intervention.
• Studies to assess the initial feasibility of a mind and body complementary or integrative health approach (i.e., feasibility should have already been demonstrated in at least a single site), or those proposing substantial adaptations to an existing intervention.
• Fully remotely delivered clinical trials.
• Studies that do not include a mind-body intervention.
• Studies that propose a waitlist control.
• Studies that are geographically limited (e.g., recruiting from one city or region).
• Trials that propose to assess feasibility of interventions for the treatment or prevention of cancer. (Investigators interventions for the treatment or prevention of cancer. (Investigators interested in cancer treatment or prevention trials should contact the National Cancer Institute.) 

Plan for Enhancing Diverse Perspectives (PEDP)

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

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

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

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

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

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

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

Federal Governments

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

Other

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

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

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

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

Applicant Organizations

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

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019 and Notice of NIH's Interest in Diversity, NOT-OD-20-031.

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.

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

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

Plan for Enhancing Diverse Perspectives (PEDP)

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

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

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

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

• Selection or hiring of personnel for a research team based on their race, ethnicity, or sex.
• A training or mentorship program limited to certain researchers based on their race, ethnicity, or sex.

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

SF424(R&R) Senior/Key Person Profile

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

Biographical Sketches: Document the PD/PI’s experience in leading clinical trials and expertise in the content area of the trial (e.g., intervention, study population, research methods). Even feasibility clinical trials will require a multidisciplinary team (e.g., clinician, biostatistician, data manager, study coordinator), and the application should reflect their hands-on involvement in the design and implementation of the study protocol. Applicants are encouraged to provide strong evidence of the study team’s qualifications and ability to conduct the proposed as well as future research, experience as investigative team members, and previous investigative experience in related clinical trials. 

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. Applicants are encouraged to provide strong evidence of the study team’s qualifications and ability to conduct the proposed as well as future research and previous investigative experience in related clinical trials. 

R&R or Modular Budget

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

The budget for the first year of the grant should reflect the time needed for trial startup. 

Applicants are strongly encouraged to request no more than $350,000 direct costs per year for up to 3 years of support. The request of a longer project period or higher per-year costs must be extremely well justified, specifying why the costs exceed those of a typical multi-site feasibility trial. The budget for the number of participants included in the trial should be based on the number of participants needed to demonstrate feasibility outcomes, not on the power for assessing efficacy on a clinical outcome, which will not be supported by this NOFO. 

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 (see https://www.nccih.nih.gov/grants/policies/data-and-safety-monitoring-of-nccihfunded-clinical-research). 

PEDP implementation costs:

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

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

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, the 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 to include a discussion of how the future trial will test the proposed hypotheses and how or why there is clinical equipoise. The application should clearly state the need for and timeliness of both the future trial and the proposed multi-site feasibility trial, emphasizing how the results will address an evidence gap and therefore advance knowledge of theory and practice in this area. A discussion of the costs and benefits of the future trial should be included for evaluation of the trial’s significance. 

The importance of the proposed multi-site 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 multi-site feasibility hypothesis 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 the 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 achieve positive results, 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 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, clinical trial experience, and the experimental approach.

Supporting data: The studies that led to the proposed clinical trial should be presented. Data from pilot studies conducted by the team or published in the literature that show the need for and feasibility of the trial should also be presented. Additional supporting data from other research should be included so the approach chosen is clearly justified and adequately framed. Applications must include the following preliminary data from human studies (preferably published in the literature) using a similar intervention in a similar population to the one proposed in the current study: 

All of the following preliminary data about the intervention (from published literature or the team’s previous research): 

• Demonstration that a similar intervention to the one proposed in the trial is well tolerated (does not produce frequent severe adverse events) in pilot human studies. 
• Single-site feasibility data on a similar intervention in a clinical population similar to the one that will be studied in the proposed trial (e.g., a proposed study to examine vinyasa yoga in adults with anxiety may cite pilot work on hatha yoga in a population of adults with depression and anxiety).  
  • Demonstrated adherence (e.g., cite a pilot study of a similar duration with sufficient adherence). 
  • Demonstrated retention of participants for a similar study duration (e.g., cite a pilot study that retained a sufficient percentage of participants at the primary outcome time point). 
• Information to justify the selection of how the intervention is delivered (e.g., format of delivery, duration of individual intervention, frequency of delivery, and timeline of intervention delivery to achieve clinical benefit) in the study. For example, the intervention could be delivered as a single 30-minute session once a week for 8 weeks, or as self-paced 5-minute modules over 10 weeks. Preliminary data should demonstrate that the selected doses are feasible and likely to have the greatest impact on clinical outcome and minimize the risk of adverse events. 
• 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 natural product proposed has demonstrated efficacy for the condition being studied from at least one fully powered placebo-controlled trial. 

All of the following preliminary data demonstrating the collective team’s experience conducting clinical trials: 

• Delivered a similar intervention via the same delivery mode in a single site clinical trial with fidelity. 
• Successfully recruited and accrued similar participants. 
• Successfully randomized participants to similar intervention and control conditions.  
• Achieved adherence to a similar intervention study protocol by research staff. 
• Retained participants for a similar study duration. 
• Completed collection of follow-up data with consistency and minimal missing data.  
• Published results from previous completed trials. 

Experimental Approach: A summary of the proposed multi-site feasibility trial protocol should be presented in the research strategy and should include the items listed below. 

• Without duplicating the information in PHS Human Subjects and Clinical Trials Information form, provide a description of why the target population is an appropriate group for addressing the proposed hypotheses and how or if results can be generalized 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 for assessing fidelity of intervention delivery and intervention performance, time duration of delivery (for clinician-provided interventions) or participant practice (for 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 diversity of their participant population. 
• A description of the commitment to engagement of the clinical community that will play a critical role in the recruitment, retention, and overall conduct of the clinical trial, including how this clinical trial will be prioritized in the context of other overlapping clinical research. 
• 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. 
• A description of the strategy for timely publication and dissemination of results. 
• Description of a future clinical trial: a concise summary of the proposed subsequent fully powered trial, including the study design (efficacy, effectiveness, or pragmatic) and how the proposed multi-site feasibility study will inform the design of that 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 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 Investigational Device Exemption (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 is necessary to the successful conduct of the trial should be provided from all participating sites or community organizations. 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. 

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. 

Specific to this NOFO: 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. 

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) planned remote recruitment methods, including use of contact lists, databases, other pre-screening resources, advertisements, outreach, media/social media, and referral networks or groups; (2) any known (based on literature or prior experience) participant or study-related barriers to accrual or participation (list the 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 NCCIH Policy: Study Accrual and Retention for Human Subject Research (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 diverse sample of eligible participants to demonstrate feasibility of meeting the NIH requirements for a representative sample in the future fully powered efficacy or effectiveness trial. 

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 NCCIH’s 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 remotely 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, recommend whether the protocol should be modified, and, at each meeting, recommend whether the study should continue or be 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 peer review, or even inquire about 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 (e.g., botanicals, probiotics, and products marketed as dietary supplements), or drug, this attachment should describe correspondence from the FDA indicating whether the proposed study will require an IND or IDE application. Investigators should describe the process and the associated timeline that will be used to attain all FDA or other applicable regulatory agency approvals necessary to the conduct of the trial. For trials using an FDA-regulated product that requires an IND or IDE application, the grant application must include evidence regarding the outcome of a pre-IND meeting, or other evidence of communication with the FDA. If the protocol is being 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 or 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 for substances that are Generally Recognized as Safe (GRAS) that 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 the FDA requires an IND application for the proposed clinical trial, the IND application must be submitted to the FDA, with no clinical hold imposed by the FDA before the application is funded. 

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 application. Attachments permit expansion of certain elements that cannot be appropriately described in the Research Strategy. All attachments listed below must be provided or the application will not be peer reviewed. 

1. Clinical Trial Experience 

Applicants must provide a detailed table listing the characteristics of trials that demonstrate key personnel experience in trial coordination in the past 5 years. One table must be provided for each study record, with a unique filename for each study record as an attachment (e.g., “Clinical Trial Experience1.pdf”" "Clinical Trial Experience 2.pdf," etc.), and must not exceed three pages. 

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 was completed on schedule 
• Publication reference(s) 

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.   

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

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

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

Important reminders:

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

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply - Application Guide.

See more tips for avoiding common errors.

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

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, 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.

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. 

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

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

Post Submission Materials

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

In addition to the post-submission materials allowed by NIH Policy and described in NOT-OD-19-083 (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-19-083.html), the following post-submission materials are allowed:  

• Revised Clinical Trial Experience Table (e.g., due to updated enrollment numbers, publication of trial results, or newly started clinical trials). 
• 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.

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

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. 

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.

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.

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, including the PEDP, as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

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

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

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

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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

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

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

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

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

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

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

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

2. Administrative and National Policy Requirements

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

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

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

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

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:

1. ongoing and consistent access to HHS owned or operated information or operational technology systems; and 
2. 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. 

Not Applicable

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.

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

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

Section VII. Agency Contacts

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

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

Finding Help Online: https://www.era.nih.gov/need-help (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

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

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

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

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

Debbie Chen
National Center for Complementary and Integrative Health (NCCIH)
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 2 CFR Part 200.