PAR-28-091-Full-Announcement.html

Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Center for Complementary and Integrative Health (NCCIH)

Note: Not all NIH Institutes, Centers, and Offices (ICOs) participate in Announcements. Applicants should carefully note which ICOs participate in this announcement and view their respective areas of research interest at the ICO-Specific Scientific Interests website. ICOs that do not participate in this announcement will not consider applications for funding.

Funding Opportunity Title

Assessing the Feasibility of Incorporating Mechanisms in Multi-site Clinical Trials of Mind and Body Interventions on Whole Person Health Restoration (R33 Clinical Trial Required)

Activity Code

R33 Exploratory/Developmental Grants Phase II.

Announcement Type

New

Related Notices

Check for any recent Notices of NIH Policy Changes that may impact application requirements.

Funding Opportunity Number (FON)

PAR-28-091

Companion Funding Opportunity

None

Number of Applications

See Part 2, Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s)

93.473, 93.213

Funding Opportunity Purpose

The National Center for Complementary and Integrative Health (NCCIH) announces this Notice of Funding Opportunity (NOFO) to solicit applications for multi-site feasibility trials of complementary and integrative health approaches with physical and/or psychological therapeutic inputs (often called mind and body interventions) to reproduce and translate mechanisms of emotional well-being (EWB) into large-scale clinical trials that advance our understanding of whole person health. These early-phase multi-site trials are essential for 1) demonstrating that the mind and body intervention can be delivered with fidelity across sites; 2) demonstrating reproducibility and rigor in engaging targeted mechanisms of EWB by the mind and body intervention across sites; 3) assessing feasibility of participant recruitment and retention, as well as randomization; 4) assessing feasibility of collecting comprehensive clinical (whole person health restoration) and mechanistic (EWB) data across sites; and 5) exploring correlations between changes in mechanistic targets and clinical outcome measurements pooled across sites. By laying this groundwork, studies supported under this NOFO will advance the science of whole person health and prepare the field for rigorous clinical trials and mechanistic mediation analysis with the potential to improve the health and well-being of all Americans.

Funding Opportunity Goal(s)

NCCIH is the lead Federal agency for scientific research on the fundamental science, usefulness, and safety of complementary and integrative treatments and practices. To address the need for objective evidence on the fundamental science, safety and efficacy of complementary and integrative health approaches, NCCIH supports rigorous scientific investigation to better understand how these interventions impact health, for whom, and the optimal methods of practice and delivery.

Key Dates

Posted Date

October 15, 2026

Open Date (Earliest Submission Date)

January 16, 2027

The following table includes NIH standard due dates marked with an asterisk.

February 16, 2027 *

March 16, 2027 *

Not Applicable

December 2027

June 16, 2027 *

July 16, 2027 *

Not Applicable

April 2028

October 16, 2027 *

November 16, 2027 *

Not Applicable

July 2028

February 16, 2028 *

March 16, 2028 *

Not Applicable

December 2028

June 16, 2028 *

July 16, 2028 *

Not Applicable

April 2029

October 16, 2028 *

November 16, 2028 *

Not Applicable

July 2029

February 16, 2029 *

March 16, 2029 *

Not Applicable

December 2029

June 16, 2029 *

July 16, 2029 *

Not Applicable

April 2030

October 16, 2029 *

November 16, 2029 *

Not Applicable

July 2030

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

Expiration Date

November 17, 2029

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.

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 Chronic diseases are a major health and economic burden. Approximately 60% of Americans live with at least one chronic condition, such as heart disease, diabetes, depression, and cancer. These conditions account for 8 of the 10 leading causes of death in the United States. In addition, 90% of the nation's $4.5 trillion in annual health care expenditures are for people with chronic conditions (CDC, 2024).

However, health and disease are not separate, disconnected states. Rather, they exist along a continuum in which a person can move toward or away from a state of health (Quinlan, Baumgartner et al., 2024). The process by which individuals travel from a less healthy state to a healthier state can be referred to as health restoration. Aligned with the Making America Health Again (MAHA) and National Institutes of Health (NIH) priorities to improve population health, there is a critical need to develop rigorous and reproducible science that identifies the pathways and interventions that reduce chronic disease and promote health restoration.

One way to assess health restoration is to explore positive changes in whole person health. Whole person health involves looking at the whole person – not separate organs or body systems – and considering multiple interconnected factors that influence health. Instead of just treating one specific disease, whole person health focuses on restoring health and preventing disease across the lifespan. To support this approach, NCCIH, in collaboration with the Centers for Disease Control and Prevention (CDC), developed and validated the current gold standard measurement of whole person health: the Whole Person Health Index. This comprehensive measurement captures key domains contributing to health, including diet, physical activity, chronic stress, sleep, and quality of life.

Mind and body interventions are widely used by the public for pain management, stress reduction, general health maintenance, and increasingly for improving emotional well-being (EWB) (Nahin et al., 2024). Emotional well-being is a multidimensional construct that includes positive emotional experiences, a sense of meaning and purpose in life, and overall life satisfaction (Park et al., 2023). To advance the science of EWB, NCCIH partnered with multiple NIH Institutes, Centers, and Offices to establish the Emotional Well-Being: High Priority Research Networks.

The funded Emotional Well-Being Research Networks and broader literature have identified promising mechanisms supporting EWB that may drive improvements in whole person health. However, much of the existing evidence comes from single-site or small-scale studies. This limits confidence in reproducibility, generalizability, and readiness for translation to clinical trials conducted in real-world settings. Before conducting fully powered efficacy or effectiveness trials, NIH Gold Standard Science (GSS) principles require strong preliminary evidence.

Research Objectives This NOFO will support multi-site feasibility trials to collect preliminary evidence that:

Consistent with NIH Gold Standard Science principles, multi-site feasibility clinical trials are the necessary next step and can serve as a translational bridge between mechanistic discovery and fully powered efficacy and mediation studies.

Scientific Areas of Research Interest Examples of EWB mechanisms include, but are not limited to:

Applications Not Responsive to this NOFO The following types of applications are not responsive to this NOFO and will not be reviewed:

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

Revision

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

Application budgets are not limited but are strongly encouraged not to exceed $500,000 in direct costs per year, reflecting the translational and multi-site nature of this work. Budgets exceeding these guidelines will be considered only in exceptional circumstances and must be extremely well justified.

Award Project Period

Applicants are strongly encouraged to request no more than 3 years unless there is a strong scientific justification related to multi-site clinical and mechanistic feasibility assessment and cross-site reproducibility of target engagement. The maximum allowable project period is 4 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

Nonprofits Other Than Institutions of Higher Education

For-Profit Organizations

Local Governments

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/International Collaborations

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 not 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. Foreign organizations must obtain a NATO Commercial and Government Entity (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.

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. Obtaining an eRA Commons account can take up to 2 weeks.

All PD(s)/PI(s) must be registered with ORCID. The personal profile associated with the PD(s)/PI(s) eRA Commons account must be linked to a valid ORCID ID. For more information on linking an ORCID ID to an eRA Commons personal profile see the ORCID topic in our eRA Commons online help.

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).

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 (in this NOFO, in a policy notice, or other notice from NIH Guide for Grants and Contracts). 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

SF424(R&R) Senior/Key Person Profile

R&R Budget

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 $500,000 direct costs per year for 3 years of support. The request for a longer project period or higher per-year costs must be extremely well justified. The maximum allowable project period is 4 years. The budget for the number of participants included in the trial should be based on the number of participants needed to demonstrate feasibility benchmarks, 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).

R&R Subaward Budget

PHS 398 Cover Page Supplement

PHS 398 Research Plan All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

In general, applicants should keep the following in mind, regarding:

Preliminary Data Requirements The following preliminary data from previous single-site studies from published literature or the team's previous research are required:

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.

Study Design Considerations For this Notice of Funding Opportunity (NOFO), the proposed multi-site feasibility clinical trial must enroll research participants from at least two sites that are geographically distinct (e.g., recruiting from more than one city or region). Sites should be non-overlapping with respect to clinical trial populations and should support the recruitment of a representative sample.

All studies are required to include the Whole Person Health Index and an EWB mechanism as part of their data collection protocol. Such a design should demonstrate that the collection of both clinical and mechanistic measures is feasible across sites. This also provides justification for testing a model in the future by which intervention-related changes in the clinical outcome are mediated through the EWB mechanism. This approach is intentionally designed to demonstrate rigor and reproducibility of target engagement and facilitate translation. Additional measurements of other clinically relevant and validated outcome measurements capturing positive movements toward health (i.e., health restoration) may also be included.

Investigators should propose a randomized controlled trial design with at least one intervention arm and one comparator arm. The intervention arm must include a mind and body intervention. There should be strong scientific rationale for the comparator condition (e.g., time and attention control, usual care, standard of care, sham condition, and/or active comparator). The selection should align with the research question to be addressed in the future fully powered trial. Waitlist comparator conditions are not allowed due to lack of rigor and expectancy effects.

Applications that do not follow the study design requirements stated above will be considered non-compliant and withdrawn prior to review.

Multidisciplinary collaborations are strongly encouraged. Teams may include experts in mind and body research, clinical care, biology, psychology, neuroscience, physiology, and related fields. Such collaborative, team-science supports innovation and advances the mission of the National Institutes of Health (NIH).

Statistics and Power Pilot or feasibility studies are conducted to prepare for future adequately powered trials. These studies should focus on key issues of process (e.g., recruitment, retention, adherence, and/or fidelity) and feasibility of outcomes assessment (e.g., data collection methods, frequency, burden, and duration). Multi-site feasibility trials submitted under this NOFO are not allowed to include aims to assess the efficacy/effectiveness of an intervention on clinical outcomes or evaluate mediation effects. Statistical methods for clinical outcomes should be descriptive.

Investigators must collect mechanistic measures of EWB across sites to reproduce target engagement. They must also assess correlations between mechanistic and clinical measures (including the Whole Person Health Index) to inform future mediation analysis. Studies should be powered to reproduce the impact of the mind and body intervention on the target EWB mechanism observed in a previous study.

Group-Based Interventions In some cases, investigators 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. Study designs should align with intervention delivery and account for contamination and logistical considerations. Applicants should demonstrate that their methods are appropriate for participant assignment and intervention delivery. Refer to the Research Methods Resources website for additional information.

Applications should also address the following criteria:

Importance of Research

Rigor and Feasibility

Expertise and Resources Applicants should describe relevant prior experience demonstrating the team's collective ability to conduct clinical trials, including:

Applications should also provide evidence of multidisciplinary research experience and documentation demonstrating the availability of eligible participants at each site.

Letters of Support Provide letters of support from clinicians or department chairs at all participating sites whose involvement is necessary for successful study conduct. Applicants are encouraged to include documentation confirming commitment from subcontractors and consultants, as well as service agreements for personnel and facilities. Letters of commitment must be co-signed by the business official of each collaborating center. If other sources will support trial costs, include letters of support signed by an authorized representative.

If the intervention includes a natural product, provide a letter of support confirming that sufficient supply will be available at the time of award, including expiration date. The supplier will meet Chemistry, Manufacturing, and Controls (CMC) specifications and provide necessary data to support compliance with NIH policies and Food and Drug Administration (FDA) regulations. The 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:

A Data Management and Sharing Plan (DMS Plan) is required for any NIH-funded or conducted research that will generate scientific data. Applicants must submit the DMS Plan at the time of application using the NIH DMS Plan Format Page. The DMS Plan must address the elements in the structured format. Where the DMS Plan Format Page requires a "Yes or No" response, no additional narrative is allowed.

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

Section 2 - Study Population Characteristics

2.5 Recruitment and Retention Plan

Describe the following: (1) planned 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.

Study Accrual and Retention for Human Subjects Research To ensure ethical conduct, scientific integrity, and appropriate stewardship of public funds, NCCIH requires all clinical research supported under this NOFO to include a Study Accrual and Retention Plan (SARP) prior to initiation of participant enrollment. Accrual and retention benchmarks should be realistic and tailored to the study design and target population, specifying the anticipated start of enrollment, the number of participants to be accrued over defined time periods, and projected retention rates through study completion. NCCIH and the grantee will agree to these benchmarks, which will be formally reviewed and approved prior to initiation of clinical research activities.

Once enrollment begins, grantees must monitor and report accrual and retention progress at regular intervals. NCCIH compares actual performance against the agreed benchmarks and will work collaboratively with grantees to identify and address accrual challenges early in the study. Persistent accrual or retention shortfalls relative to the approved benchmarks may prompt enhanced monitoring, requests for corrective action plans, adjustments to trial operations, or other NIH actions to optimize study feasibility and protect participant welfare. This accrual and retention framework ensures that clinical studies have a high likelihood of meeting their aims and generating meaningful contributions to scientific knowledge.

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.

Data and Safety Monitoring All clinical research supported under this NOFO must include a Data and Safety Monitoring Plan (DSMP). The DSMP must clearly describe procedures for monitoring participant safety, protecting data integrity, and ensuring study quality throughout the conduct of the trial. The monitoring plan must specify:

The DSMP 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 Investigational New Drug (IND) or Investigational Device Exemption (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:

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

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.

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 Grant Self Disclosure Program at grantdisclosures@oig.hhs.gov.

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

Section V. Application Review Information

1. Criteria Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

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)

Innovation

Factor 2. Rigor and Feasibility (Approach)

Rigor: