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.

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Background

Although animal models are extremely valuable in aging research, they do not always phenocopy human aging, and they provide limited insight into human-specific mechanisms underlying aging. Furthermore, for some aging-related diseases and conditions, there are no suitable animal models available. Human-based in vitro models that complement animal and clinical studies may be used to gain a deeper understanding of the mechanisms underlying the aging process, and the etiology and progression of various age-related conditions. Advantages of in vitro models include the option for genetic manipulation, controlled cellular environmental conditions, and the ability to study responses to perturbations.

The advent of technologies for culturing 3D human MPS opens opportunities to model aging with multi-cellular in vitro systems. These systems are amenable to pathophysiology mechanistic studies, discovering and testing of interventions, and investigations into human heterogeneity. MPS are systems that use microscale cell culture platforms for in vitro modeling of functional features of a specific tissue or organ by exposing cells to a microenvironment that mimics the physiological aspects important for their function or pathophysiological condition. Examples of MPS include, but are not limited to, tissue-chip, organ-on-chip, and organoid. While there are successful examples using MPS for disease modeling, their use to model aging and age-related conditions and phenotypes has not yet been fully developed. Current approaches include the use of donor's induced pluripotent stem cell (iPSC)-derived differentiated cells organized into 3D tissues or self-assembled organoids. During reprogramming to generate iPSCs, most of the “historic” memory of the donor cell is erased and an age-induction step (e.g., using stressors or modifying the physical/nutritional environment) is necessary to re-establish an aging phenotype. For neuronal and few other tissues, the aging signature of the donor has been successfully retained (albeit with variable efficiency and yield) by direct reprogramming of somatic cells. 

Research Objectives and Scope

This NOFO solicits projects to develop human MPS that recapitulate aging in vitro with the goal to robustly and reproducibly model how human tissues and organs age in vivo. Projects that will develop MPS based on nonhuman mammalian cells are acceptable if used for benchmarking and system validation in parallel with the corresponding human MPS and/or when the similarity between the nonhuman tissue/organ and its human counterpart justifies the relevance of the nonhuman system to understanding human aging biology. These interdisciplinary projects are expected to advance the validation and adoption of MPS for aging research or as new human-relevant tools for drug discovery. Multidisciplinary teams must comprise expertise in aging biology and additional disciplines such as stem cell biology, tissue and organ physiology, microfluidics, bioengineering, computational biology, pharmacology, and biostatistics.

This NOFO supports innovative multidisciplinary approaches, high risk, high impact designs to develop mammalian MPS that recapitulate one or more aging processes/phenotypes as novel models to investigate human aging. Preliminary data are not required. All tissues and organ types are acceptable as long as the target aging phenotype(s) are clearly defined and appropriate. In the absence of consensus on biomarkers of aging, applicants must provide justification for the use of reliable/rigorous aging-sensitive phenotypes (e.g., hallmarks of aging or disease-specific biomarkers) as surrogate biomarkers. Of particular interest are projects that propose benchmarking MPS against whole organism or clinically relevant human data.

The scope of the research must address the challenge to faithfully and reproducibly recapitulate aging processes/phenotypes in vitro. It may include the design of new tools/assays to analyze molecular and cellular phenotypes in vitro at end-points or over the duration of the experiment. It must define the constraints within which investigation of aging can be pursued and what questions are best addressed using the proposed in vitro system(s). It should discuss what characteristics of the proposed MPS will facilitate its establishment and wide adoption as a tool to study aging and how it will complement research in live animals and clinical studies.

The proposed mammalian 3D in vitro tissue systems must be relevant for human aging research. They will recapitulate the minimal tissue complexity and microenvironment to elicit physiological features comparable to the in vivo human aged tissue or organ type. Such tissue constructs will be utilized to investigate molecular and cellular aging phenotypes retained from the donor or induced with different experimental approaches. When the source of cells are human donors, they should allow for the identification of mechanisms/pathways of aging that are unique to humans and, where possible, include subjects that are representative of the heterogeneity in the population. When nonhuman mammalian species are used as the cell source, they should facilitate benchmarking against corresponding in vivo aging whole organisms.

Areas of Interest

The proposed MPS may be based on cells derived from human donors (e.g., from biopsies, therapeutic surgical interventions, or post-mortem) or from iPSC-derived cells/tissues. When derived from nonhuman primary cells or iPSCs, the choice must be justified by the relevance of the model to human aging.

Examples of in vitro model systems include, but are not limited to:

• Human organoids, tissue/organ-on-chip that recapitulate molecular, cellular or physiological features of aging
• Tissues comprising multiple cell types organized in functional units that are characteristic of the human tissue and its aging phenotype(s)
• Multi-organ systems to investigate human organ-to-organ communication and the emergence of aging phenotypes
• MPS generated using cells from human donors with genetic predisposition to or manifesting diseases of aging, or premature aging syndromes

Responsiveness Criteria

Applications addressing, but not limited to, the following topics with the goal to recapitulate one or more phenotypes of aging are responsive to this NOFO:

• Development of a new in vitro system
• Increasing the complexity of an existing system
• Validating protocols for recapitulating aging in vitro

Non-Responsiveness Criteria

Applications addressing the following topics are not responsive to this NOFO and will be withdrawn prior to review:

• Developing MPS (1) that are not informative about cell, tissue or organ aging, (2) that do not include more than one cell type, (3) using mammalian cells/tissues that are not directly relevant to human aging, and (4) that employ tissue explants/organotypic cultures
• A central focus on scaling assays or adapting for use in compound screening
• Strategies directed toward cell therapy or regenerative medicine
• Utilization of existing technologies that are not well justified to advance the state of the art to address aging-relevant questions

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 - Includes all types

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

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

Federal Governments

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

Other

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

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.

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. 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.

SF424(R&R) Senior/Key Person Profile

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

Multidisciplinary teams must comprise expertise in aging biology and additional disciplines such as stem cell biology, tissue and organ physiology, microfluidics, bioengineering, computational biology, pharmacology, and biostatistics.

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:

The primary focus of applications responding to this NOFO should be developing human MPS that recapitulate one or more aging phenotypes as novel models to study aging. Development of other mammalian nonhuman MPS is only responsive to this NOFO if informative to modeling human aging. All applications must define the present state of technology, address how current challenges (especially faithful and reproducible mimicking of aging phenotypes) will be overcome by the proposed MPS, and discuss what parameters will be evaluated to assess success.

The proposed in vitro system must maintain tissues in 3D in a controlled environment for a minimal length of time to provide biologically relevant outputs (e.g., molecular, cellular, physiological, etc.) mimicking aging or diseases associated with aging. Of particular interest are MPS that replicate in vivo aging physiological processes less accessible to direct investigation in human and that are amenable to real-time detection of phenotypic changes (e.g., through sensors and data acquisition).  Performance of the system should be characterized and validated using clearly defined metrics. Applications must include milestones, quantifiable deliverables and criteria to define success in establishing an in vitro human-relevant model of aging.

The research strategy must address the following four elements:

1) Definition of the 3D in vitro system

• Description of the MPS that recapitulates human molecular, cellular, and/or physiological aging phenotypes.
• Discussion of how the challenges of faithfully and reproducibly recapitulating aging processes/phenotypes are addressed by the proposed MPS.
• Definition of the constraints and what questions are best addressed by the proposed MPS.
• When human-based, the system should be developed from cell/tissues from human donors and/or human induced pluripotent stem cell (iPSC)-derived cells/tissues.
• When nonhuman cell-based, the system must be derived using primary cells or iPSCs from a mammalian species. A justification must be included to support the relevance of the model to understanding human aging.
• The MPS must include more than one cell type to closely resemble the tissue of origin and may include the vasculature and/or immune and/or neuronal cells to better recapitulate tissue physiology and aging.
• The strategy must include considerations about control of tissue environment (e.g., oxygen tension, access to nutrients).

2) Explanation of the approach(es) adopted to attain aging. Possible strategies include but are not limited to:

• Incorporating an aging component into a pre-existing MPS of one or more tissue types or organs.
• Directing tissue maturation and aging by increasing cell complexity and tissue connectivity.
• Introducing stressors, inducing DNA/cell damage, environmental stimuli, or exposing the tissue to progeroid factors.
• Incorporating in the system cells harvested from aging donors, directly reprogrammed if necessary.
• Establishing the system with cells carrying genetic mutations that confer accelerated aging phenotypes.

3) Define what aging phenotypes (e.g. molecular, cellular, functional) will be measured

• Provide justification for the use of the aging-sensitive phenotypes of choice relevant to the proposed MPS.
• The research strategy may include development of sensors (e.g., molecular, devices) and software for data acquisition, real-time long-term detection and analysis and/or high-throughput measurements that are justified by the need to benchmark aging in vitro.

4) Benchmarking

• Benchmark performance of the MPS against applicable in vivo known human aging parameters (e.g., -omics profiles, physiological parameters or aging-related disease phenotypes) or in vivo animal model(s) with direct relevance to human that are widely accepted by the research community.
  • Provide evidence of modulation of one or more measurable biological hallmark of aging or markers of disease of aging.

This research approach is most successful when tools, cell lines, engineering designs, etc., are shared. Therefore, the successful investigators will participate in a consortium to develop new tools for MPS applications in aging research, with set periodic meetings, forums and shared resources. Successful investigators will also be invited to join the National Center for Advancing Translational Sciences (NCATS) Tissue Chip Consortium.

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.

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.

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 NIA, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

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

Section V. Application Review Information

1. Criteria

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

For this particular announcement, note the following:

The R21 Exploratory/Developmental Research Grant activity code supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. An R21 application need not have extensive background material or preliminary information. Accordingly, reviewers will emphasize the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.

Since this NOFO encourages innovative approaches with major methodological challenges, the level of risk is generally expected to be higher than for conventional R21 applications. As a result, reviewers should primarily assess merit based on the technical achievements and capabilities of the proposed cell-based models relative to current state of the art.

Applications may focus on technology development that is at the early conceptual stage. Development of a prototype in vitro MPS that is sufficient to generate preliminary data and that has the potential to be further developed in future efforts for validation as in vitro model of aging should be considered of high significance. Projects need not include investigation of specific biological questions using the proposed in vitro system to attain high significance.

Benchmarking (i.e., comparison of the MPS with other models or human data) is required, whereas validation (i.e., assurance of the accuracy) of the in vitro system is welcome but not necessary at this stage. In the absence of data in the literature showing that a proposed in vitro system has already been tested and failed, the expectation should be that recapitulating aging in vitro could be accomplished in principle if the rationale and approach are sound.

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.

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 NIH’s Center for Scientific Review (CSR), 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.

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

Applications will be assigned  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 National Advisory Council on Aging. 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.

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.

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that 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.

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.

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. 

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.

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]

Tiziana Cogliati
National Institute on Aging (NIA)
Telephone: 240-397-4596
Email: [email protected]

Center for Scientific Review (CSR)
Email: [email protected]

Mitchell Whitfield
National Institute on Aging (NIA)
Telephone: 301-827-6373
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.