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 How to Apply - Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the How to Apply - Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the How to Apply - 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

Purpose

The purpose of this Notice of Funding Opportunity (NOFO) is to reissue PAR-23-256 "Feasibility Trials of the NIH Music-based Interventions Toolkit for Brain Disorders of Aging (R34 Clinical Trial Required)" in order to support proof-of-concept feasibility trials guided by the NIH Music-based Interventions (MBIs) Toolkit for research on brain disorders of aging. These early stage clinical trials will generate evidence supporting the validity of the NIH MBI Toolkit' s guiding principles as well as the necessary feasibility data to  design a subsequent clinical efficacy or effectiveness study (or pragmatic clinical trial) using music-based interventions (MBIs) in the context of brain disorders of aging, including but not limited to Alzheimer’s disease and Alzheimer’s disease-related dementias (AD/ADRD), Parkinson’s disease, and stroke. The data collected should address gaps in scientific knowledge in order to facilitate development of a competitive clinical efficacy or effectiveness clinical trial.

This NOFO will not support randomized clinical trials that propose to test or determine efficacy or effectiveness of MBIs, including preliminary efficacy or effectiveness, nor will this NOFO support repetition of feasibility or acceptability research that has been previously conducted in the same or similar patient population with the same or similar intervention. Applications that propose solely to write a protocol or manual of operations or to develop infrastructure for a clinical trial are not appropriate for this announcement. Applications must propose to conduct a feasibility clinical trial applying the guiding principles detailed in the NIH MBI Toolkit; a subsequent efficacy or effectiveness trial should have the potential to make a significant impact on public health.

Background

Empirical evidence supports that music engages many different areas of the brain and may aid in strengthening the neural networks and pathways involved in sensorimotor processes, emotion, affect, and memory. Music-based interventions (MBIs) may represent a valuable therapeutic opportunity for a wide range of disorders impacting these domains, especially given that these interventions are frequently low-cost, mostly devoid of side effects, potentially scalable in healthcare systems, and generally well accepted by patients. However, reports of the beneficial effects of music on human health have largely emerged from anecdotal evidence of small-scale clinical trials, and the scarcity of data from rigorous, well-powered studies presents a major limitation to widespread application of MBIs.

Harnessing the therapeutic potential of music is of wide interest across NIH: 21 of NIH’s 27 Institutes and Centers have representatives in the Trans-NIH Music and Health Working Group. This group supported the issuance of three NOFOs in 2019 that were designed to promote research on music and health. Two of these NOFOs (RFA-NS-19-008 and RFA-NS-19-009) supported R01 and R21 awards, respectively, for research related to the fundamentals and application of music in health. The third NOFO (RFA-AT-19-001) utilized a phased R61/R33 mechanism to support research on music and health geared toward the development of MBIs. These NOFOs were followed in 2020 by the publication of three program announcements with special reviews (PAR-20-266, PAR-21-100, and PAR-21-099) to continue NIH’s support for basic, mechanistic, translational, and clinical research on music and health.

In 2021, NIH collaborated with the Foundation for the NIH (FNIH) and the Renée Fleming Foundation to organize three workshops: Laying the Foundation: Defining the Building Blocks of Music-Based Interventions, Assessing and Measuring Target Engagement Mechanistic and Clinical Outcome Measures for Brain Disorders of Aging, and Relating Target Engagement to Clinical Benefit Biomarkers for Brain Disorders of Aging. Each workshop featured interdisciplinary panels of experts in neuroscience, music therapy and music medicine, behavioral intervention development, clinical trial methodology, and patient and arts advocacy. Notably, each expert panel   included both scientists actively working in the field of music and health as well as experts in a relevant discipline but not directly involved in MBI research, thus bringing fresh and unbiased perspectives to every panel. The NIH MBI Toolkit, which was recently published by the journal Neurology, is a direct outcome of these workshops that addresses a pressing need for building blocks of music-based interventions, use of a core set of common data elements, recommended functional outcome measures and biomarkers, and a framework and guidelines for music-based intervention research  to  enhance  the rigor and reproducibility of MBI studies.

This R34 NOFO will support proof-of-concept feasibility trials guided by the NIH MBI Toolkit for research on brain disorders of aging. These early stage clinical trials will generate evidence to determine the validity of the NIH MBI Toolkit’s guiding principles as well as the necessary data to design a subsequent clinical efficacy or effectiveness study (or pragmatic clinical trial) using MBIs in the context of brain disorders of aging, including but not limited to AD/ADRD, Parkinson’s disease, and stroke. The NIH MBI Toolkit defines the essential components of MBIs and promotes inclusion in MBI studies of critical elements that enhance rigor and reproducibility, such as a conceptual model or framework to guide the design of the MBI, a clear research question, and supporting data for the hypothesis. The NIH MBI Toolkit also outlines a core set of common data elements or building blocks that must be included in every MBI, including a comprehensive description of the intervention, a detailed protocol for delivering the intervention, a defined population to be studied, and control groups or comparators. Validation, dissemination, and implementation of the NIH MBI Toolkit’s guiding principles are viewed as critical steps toward accumulating the large-scale, rigorous, and replicable evidence necessary to incorporate MBIs into clinical practice.

Requirements and Scope

This NOFO proposes to build upon the rapidly expanding evidence base linking music and health by supporting feasibility trials guided by the NIH MBI Toolkit for brain disorders of aging. The R34 planning grant will support planning activities and analyses of existing data needed to design a feasibility and acceptability clinical research project and develop a protocol, to gather data to prepare for a future efficacy trial. . The grant will also support new data collection for assessing feasibility of protocol components (e.g., recruitment strategies, outcome ascertainment). Applicants are encouraged to review NCCIH guidance on appropriate components of a feasibility study. Since the focus of this NOFO is on the feasibility of the intervention, delivery of the intervention must be limited to one site.

All projects should be rigorously designed according to the guiding principles of the NIH MBI Toolkit and within the mission of the participating Institutes, Centers, and Offices. In addition, all proposed projects should have the potential to increase our understanding of the science of music and health, as well as inform MBIs to enhance normal function and improve health using brain disorders of aging as a model system.

Applications to this NOFO must also address the following specific requirements:

• State the conceptual framework (e.g., music therapy, behavioral, neural, social) guiding the proposed research (example frameworks are described in the NIH MBI Toolkit)
• Address all MBI building blocks as outlined by the NIH MBI Toolkit
• Identify relevant clinical outcomes and/or biomarkers for brain disorders of aging (examples are provided in the NIH MBI Toolkit)
• Propose a multidisciplinary research team with expertise such as clinical trial design, music therapy/music medicine, behavioral intervention development, neuroscience, social science; patient-caregiver engagement is also encouraged.

Prospective applicants should note that funding of a planning grant does not guarantee or imply funding for any subsequent competitive application for support of a full-scale, multi-site clinical trial or clinical research study.

The following are examples of project goals that are appropriate for feasibility trials submitted in response to this NOFO when the literature has not already demonstrated evidence for the proposed (or a similar) intervention and study population:

• Examine feasibility and acceptability of various conceptual models or frameworks of MBIs (e.g., music therapy, behavioral, neural, or social)
• Examine feasibility and acceptability of MBIs lacking published data for brain disorders of aging
• Adapt an MBI to a specific population or disease stage relevant to brain disorders of aging
• Assess acceptability and adherence to frequency and/or duration of an MBI for testing in a future large-scale, multi-site efficacy or effectiveness clinical trial
• Determine feasibility of recruitment, retention, and data collection procedures
• Develop and assess the feasibility of defined protocols for multimodal MBIs
• Assess the feasibility and acceptability of recruitment, retention, intervention delivery, and data collection procedures of a fully remote MBI intervention
• Examine acceptability and adherence of control conditions for MBIs and brain disorders of aging
• Refine an MBI to address challenges with intervention fidelity, participant adherence or retention, selection of appropriate outcomes, and ability to capture outcome measures within designated time frames.
• Assess MBI acceptability and adherence at different stages of disease progression
• Assess feasibility of randomization or other aspects of trial design for MBIs in aging populations
• Test the feasibility of strategies for integrating MBIs into a healthcare system or other modes of delivery relevant to age-related brain disorders to inform design of future pragmatic trials

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 planned to be addressed in the future powered trial. Due to lack of rigor and potential expectancy effects, this NOFO will not support studies proposing a waitlist comparator condition.

Power Recommendations 

Pilot or feasibility studies are carried out in preparation for future  adequately powered studies and, therefore, should address key issues of process (e.g., recruitment, retention, feasibility, adherence, fidelity) and/or outcomes assessment (e.g., feasibility of the method, frequency, burdensomeness, and duration of data collection procedures). Given the limited sample sizes that can be supported under this R34 grant mechanism, proposing to conduct fully powered tests of clinical outcomes (i.e., efficacy) or underpowered test of outcomes (i.e., "preliminary efficacy") or attempting to utilize the highly variable point estimate of an effect size for power calculations is not allowed and is  noted as non-responsive below. Applicants should define feasibility/acceptability with quantitative benchmarks corresponding to each assessment category.

Clinical Trials Not Responsive to this NOFO

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

• Trials that do not include an aim to assess the feasibility, acceptability, fidelity, and/or adherence to the music-based intervention 
• Studies proposing to analyze data from a feasibility trial to assess efficacy/effectiveness of an intervention or estimate effect size    
• Trials that attempt to assess safety/tolerability of a treatment
• Repeat feasibility or acceptability studies that have been previously conducted in the same or similar populations (e.g., same age range, clinical diagnosis, and other clinically relevant demographics), with the same or similar intervention, and with the same primary objectives
• Studies that do not include a music intervention  
• Studies that propose a waitlist control, due to lack of rigor and potential expectancy effects
• Trials proposing to physically administer the intervention at multiple clinical sites (i.e., multi-site trials)
• Trials that fail to propose to assess feasibility of interventions for the treatment or prevention of brain disorders of aging
• Trials that propose to assess feasibility of interventions for the treatment or prevention of cancer  (i nvestigators interested in cancer treatment or prevention trials should contact the National Cancer Institute )  
• Studies to solely develop a protocol, manual of operations, or infrastructure for a clinical trial
• Studies that  are proposing to test the efficacy or effectiveness of the music-based intervention including in a fully remote clinical trial. Applicants interested in testing the efficacy of effectiveness of a fully remotely delivered MBI can refer to PAR-24-086.
• Applications that do not utilize the guiding principles of the NIH MBI Toolkit 

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

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

Section II. Award Information

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

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 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. Conformance to the requirements in the How to Apply - Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

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

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

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

The letter of intent should be sent to:

Jessica McKlveen, PhD
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-594-8018
Email: jessica.mcklveen@nih.gov 

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.

SF424(R&R) Senior/Key Person Profile

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

R&R or Modular Budget

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

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

Significance:

The significance of the proposed clinical trial and importance of the question must be clearly stated. It is particularly important that there be a discussion of how the trial will test the proposed hypotheses and how or why there is clinical equipoise.

The clinical significance and, when applicable, the biological relevance of the future fully powered clinical trial should be clearly stated. The importance of the proposed feasibility trial should be described and why it is necessary to plan the subsequent future trial. It is particularly important that there be discussion of how the proposed early-stage trial will test the primary hypothesis focused on feasibility and how the results of the trial (positive or negative) will guide decisions about whether a subsequent study is feasible or justified, and/or evidence that additional studies must be completed before proceeding to a full-scale trial.

Applications should address the reasons for selection of the intervention. This may include public health impact if subsequent efficacy trials are conducted and positive, ethical dimensions, and patient/caregiver perspectives on acceptability of the proposed intervention. Characteristics of any preliminary research results provided in support of the proposed project, whether conducted by the applicant or others, should be described in the application so that peer reviewers may evaluate the strength of the supporting evidence. The applicant should also discuss the limitations of those data.

Innovation:

Explain how the application challenges and seeks to shift current research or clinical practice paradigms or guidelines. If not innovative, explain why alternative innovative approaches are not possible or practical and why the proposed research is necessary to establish feasibility of the intervention.

Approach:

Explain how the application addresses the appropriate regulatory requirements (i.e.,IDE, IRB).  
A summary of the proposed feasibility trial protocol should be presented in the Research strategy and should include the items listed below as described in the NIH MBI Toolkit:

• The conceptual framework (e.g., music therapy, behavioral, neural, social) guiding the proposed research (example frameworks are described in the NIH MBI Toolkit)
• The intervention characteristics, such as specific elements of music (e.g., pitch, timbre, rhythm), modes of engagement (e.g., active vs passive), dosage, frequency, or relationship to culturally specific music preferences
• Protocol delivery considerations, such as music characteristics (e.g., live vs recorded), research setting (e.g., laboratory, clinic, community), mode of participation (e.g., individual vs group, in-person vs remote), timescale (e.g., short vs long term, session length and intensity)
• Without duplicating the details from the PHS Human Subjects and Clinical Trials Information Form, a description of the study population and rationale for testing the intervention in that population
• A control group or comparator and rationale for selection; for example, the control condition may control for intervention effects that are unrelated to the music or for effects of the specific intervention protocol delivery method
• Relevant clinical outcomes and/or biomarkers for brain disorders of aging (examples are provided in the NIH MBI Toolkit)
• A multidisciplinary research team with expertise such as clinical trial design, music therapy/music medicine, behavioral intervention development, neuroscience, social science; patient-caregiver engagement is also encouraged

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): Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

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.

Study Record: PHS Human Subjects and Clinical Trials Information

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

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 last 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 the table 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(s) were completed on schedule or not
• 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.

7. Other Submission Requirements and Information

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

In order to expedite review, applicants are requested to notify the NCCIH Referral Office by email at jessica.mcklveen@nih.gov when the application has been submitted. Please include the NOFO number and title, PD/PI name, and title of the application.

Post Submission Materials

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

Any instructions provided here are in addition to the instructions in the policy.

In addition to the NIH policy allowed post-submission materials in NOT-OD-19-083, the follow post-submission materials are allowed:
Clinical Trial Experience Table (e.g., due to updated enrollment numbers, publication of trial results, or newly started clinical trials) 

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.

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

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

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

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

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NCCIH , in accordance with NIH peer review policies and practices, 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. 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:

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

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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

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

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

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

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

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

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

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

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

2. Administrative and National Policy Requirements

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

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

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

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.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to System for Award Management (SAM.gov) requirements. SAM.gov requires Federal agencies to review and consider information about an applicant in the designated integrity and performance system (currently SAM.gov) prior to making an award. 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 addition to the information available in the responsibility/qualification records in SAM.gov, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 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.

Not Applicable

3. Data Management and Sharing

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

4. Reporting

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

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH 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.

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

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

Section VII. Agency Contacts

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

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

Finding Help Online: 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: GrantsInfo@nih.gov (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: support@grants.gov

Sekai Chideya, M.D., M.P..H
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-827-1916
Email: Sekai.Chideya@nih.gov

Coryse St. Hillaire-Clarke, Ph.D.
National Institute on Aging (NIA)
Division of Neuroscience (DN)
Phone: 301-496-9350
E-mail: sthillaireclacn@mail.nih.gov

Lisa Onken, Ph.D.
National Institute on Aging (NIA)
Division of Behavioral and Social Research (DBSR)
Phone: (301) 496-3131
E-mail: lisa_onken@nih.gov

Jessica McKlveen, PhD
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-594-8018
Email: jessica.mcklveen@nih.gov

Debbie Chen
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-594-3788
Email: Debbie.Chen@nih.gov

Kathleen Moy
National Institute on Aging (NIA)
Phone: 301.827.2856
E-mail: kathleen.moy@nih.gov

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.