Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization. 

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

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

Applications that do not comply with these instructions may be delayed or not accepted for review.

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

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



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

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Background

Drug repurposing has several advantages over the development of new drugs including, shorter development times, lesser cost of development, and higher success rates. This has been done successfully for several disease conditions, however, despite multiple attempts at drug repurposing for Alzheimer's disease (AD) or AD-related dementias (ADRD) treatment, these have been without success. As we learn about the enormous complexity of AD pathophysiology and associated co-morbid conditions, it is becoming apparent that efficacious treatment for an individual patient will need to target multiple aspects of the disease and be directed towards several pathogenic processes and, as a result, require development of combination therapies.

The promise and challenges to successful drug repurposing and combination therapy development for AD were one of the major topics of discussion at the NIH AD Research Summits of  2012 ,  2015,  and  2018 and 2021 . A series of recommendations were generated from the summit discussions that called for establishing new research programs that will promote the use of systems-based, data-driven approaches to create the biomedical knowledge base, tools, and resources needed for successful drug repurposing and repositioning and combination therapy development for AD/ADRD. In 2017, NIA launched the funding initiative PAR-17-032 “Translational Bioinformatics Approaches to Advance Drug Repositioning and Combination Therapy Development for Alzheimer’s Disease”, (reissued in 2020 as PAR-20-156). The projects funded through this initiative led to the establishment of NIA's Advancing Combination Therapy and Drug Repurposing for Alzheimer’s Disease (ACTDRx AD) program. ACTDRx AD is a  cross-disciplinary program  using translational bioinformatics approaches to formulate hypotheses and identify drug candidates (individually or in combination) that may be efficacious for the treatment of AD/ADRD. The program has brought investigators working on other chronic disorders with deep expertise in data science and multiscale modeling into AD/ADRD research. Cutting edge computational methods, including artificial intelligence and machine learning approaches, have facilitated the identification of hundreds of potentially repurposable drugs. However, there remains a need to prioritize the most promising drug candidates through additional computational approaches and through rigorous and reproducible preclinical testing in mouse models or cell-based models to evaluate their PK/PD properties and efficacy against multiple AD/ADRD outcomes (molecular, biochemical, neuropathologic, functional). 

This new iteration of the program will build on NIA’s investment in data-driven approaches to AD drug repurposing and combination therapy development. This initiative is envisioned to expand current efforts with a focus on prioritization of drug candidates for repurposing and repositioning (as individual treatment or in combination with other drug candidates or non-pharmacologic interventions) and on rigorous, reproducible preclinical proof-of-concept studies in mouse models or cell-based models of AD/ADRD.

Research Objectives

The overarching goal of this Notice of Funding Opportunity (NOFO) is to support rigorous preclinical testing of drug candidates that have been identified through data-driven approaches for repositioning, repurposing, and combination therapy for t reatment and prevention of AD/ADRD. This NOFO solicits R01 applications that will conduct rigorous proof-of-concept studies using mouse models of AD/ADRD or cell-based models (such as iPSCs and organodis), to prioritize and test drugs or drug combinations predicted to be efficacious in AD/ADRD treatment and/or prevention. This initiative will also support preclinical testing of repurposable or investigational drug candidates in combination with non-pharmacologic interventions leading to robust translational outcomes.

Drugs to be tested could be FDA-approved drugs being currently used for other indications and investigational drugs that are at various stages of clinical development (for AD/ADRD or other conditions), including candidate drugs from failed Phase II/Phase III clinical trials, that have been predicted to be efficacious for the treatment and prevention of AD/ADRD. Of particular interest is robust preclinical testing of prioritized drug candidates that have been identified through NIA’s ACTDRx AD program in response to funding initiatives PAR-17-032 and PAR-20-156. Additionally, o f specific interest are projects that leverage the network concept of drug targets to advance rational drug repurposing based on the ability of single or multiple therapeutic agents to perturb entire molecular networks away from disease states in animal models and/or cell-based models (e.g., iPSCs, organoids etc.).

Academic/industry partnerships are encouraged where industry partners provide failed Phase II/III compounds and biosamples from legacy trials to enable drug repositioning and combination therapy analyses. Additionally, applicants are strongly encouraged to partner with academic and/or industry researchers with prior experience in preclinical drug development for neurodegenerative diseases.

Applications in the following categories are particularly invited, although these do not exhaust the possible approaches to drug repositioning and combination therapy development for AD/ ADRD:

• Conducting preclinical studies to establish evidence of efficacy, synergy, toxicity, target engagement, mechanism of action, route of administration, dose range, schedule of administration for repurposed drug/drug combination in relevant mouse-model systems or cell-based model systems.
• Testing individual drugs or drug combinations to evaluate efficacy and toxicity, including combining current disease treatment with a repurposed treatment or combining multiple repurposed therapies.
• Testing candidate drugs in blood brain barrier (BBB) permeability studies.
• Testing potential synergies and/or adverse events of individual drugs or drug combinations in relevant disease models.
• Assessment of PK/PD properties through the generation of multi-omic molecular data (i.e., transcriptional, epigenomic, proteomic and metabolomic) that will enable systems-level analyses to determine mechanism of action of putative drugs/drug combinations; and provide evidence that the drugs modulate disease relevant pathways/networks in preclinical/ mouse models and / or cell-based models.
• Development of quantitative, mechanistic methods that can assess the synergy or additivity of candidate therapeutics, including synergy between candidate drugs and non-pharmacological perturbations (i.e. exercise, diet, sleep, cognitive training).

Applications should propose a streamlined preclinical testing strategy with go/no-go decision points that allow critical and unbiased assessment of therapeutic agents leading to robust translational outcomes. Projects should bring together relevant technologies and a multidisciplinary team of scientists with necessary expertise including in animal models of AD, network biology, disease biology, biostatistics, PK/PD modeling, pharmacology, and clinical research to design assays and develop tools and methods that enable prioritization and rigorous testing of candidate drugs.

All preclinical efficacy testing studies should be conducted and reported in compliance with NIH guidance on rigor and reproducibility. Particularly, the preclinical efficacy studies are expected to follow the general ARRIVE guidelines for animal research and the best practice guidelines for AD preclinical efficacy studies. Applicants are strongly encouraged to use the mouse models of Late Onset Alzheimer's Disease (LOAD) developed and made available via NIA’s MODEL-AD Translational Centers. The list of available mouse models can be accessed via the  AD Knowledge Portal  and the  Model-AD explorer.

Applications to this NOFO should follow open-science, open-source principles and maximize the appropriate sharing of scientific data. Studies should adhere to NIH guidelines for rigorous study design and transparent reporting to maximize the reproducibility and translatability of their findings. All data and analytical outputs will be shared rapidly and broadly via the NIA-supported AD Knowledge Portal.

Applicants must describe and justify any applicable factors or data use limitations related to concerns of intellectual property, patents, IND filing, licensing limits, or 3^rd party contracts that will affect access, distribution, or reuse of scientific data generated from the project. Exceptions to data sharing due to these claims will be considered on an individual basis.

Applicants are strongly encouraged to contact NIA Scientific/Research staff listed in Section VII: Agency Contacts early in the pre-submission process to ensure that their application is responsive to the programmatic goals of this NOFO.

Non-responsive Applications

The following types of applications will be considered non-responsive to this NOFO and will be withdrawn prior to scientific peer review:

• Studies that propose only bioinformatics and computational approaches to discovery, prioritization or testing of drug candidates for repurposing and/or combination therapy development.
• Studies that propose research on basic mechanisms of disease.
• Studies that propose development and testing of new therapeutic agents for AD.

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

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

Federal Governments

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

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Organizations)

Non-domestic (non-U.S.) Entities (Foreign Organizations) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

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

Applicant Organizations

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

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

Program Directors/Principal Investigators (PD(s)/PI(s))

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

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

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply-Application Guide.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

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

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

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.

The PD(s)/PI(s) should have demonstrated accomplishment in effectively leading multidisciplinary teams. If the application is multi-PD/PI, investigators should have complementary and integrated expertise and skills in order to provide an appropriate leadership approach, governance, plans for conflict resolution, and organizational structure applicable to the study. The applicant(s) should have experience overseeing selection and management of sub awards, if needed.

Projects should bring together a multidisciplinary team of scientists with necessary expertise including in mouse models and/or cell-based models of AD, network biology, disease biology, biostatistics, PK/PD modeling, pharmacology, and clinical research to design assays and develop tools and methods that enable prioritization and rigorous testing of candidate drugs. 

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:

Applications should propose a streamlined preclinical testing strategy with go/no-go decision points that allow critical and unbiased assessment of therapeutic agents leading to robust translational outcomes. 

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.

In keeping with NIA’s strategic goal to enable and promote open science practices and to increase research rigor and reproducibility, recipients must make all resources (e.g. analytical methods and pipelines, network models, research tools, cell lines and animal models) developed through funded projects available to the broad scientific community via the NIA-supported AD Knowledge Portal, or through other NIH-designated repositories, and/or open-source/open-access platforms.

In keeping with the open science aspect of this funding initiative, the following will be expected from the recipients:

• All analytical methodologies, tools and pipelines, network models will be made fully reproducible and transparent so that results can be vetted and existing analysis techniques can be quickly applied to new application areas.
• All models of biological systems and networks will be openly available to users such that theoretical predictions can be rapidly validated experimentally.
• All disease models (cell lines and animal models) generated during the project will be made freely available to qualified investigators to accelerate their characterization, validation, and translational utility.
• All biological samples used to generate data with this award will be made available to all recipients of this initiative and to other qualified investigators.

Award recipients will be expected to have all resources (e.g. analytical methods and pipelines, network models, research tools, cell lines and animal models) deposited in the AD Knowledge Portal and/or other NIH-designated repositories. Awardees are expected to make all resources available after they have undergone quality control (no later than 6 months after resource generation). There will be no embargo imposed on the use of such resources after they have been made available through these repositories. Program staff may negotiate modifications to the plan prior to funding. 

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.

In keeping with NIA’s strategic goal to enable and promote open science practices and Findable, Accessible, Interoperable, and Reusable (FAIR) data practices, and the NIA/NIH goal to enhance transparent reporting and increase research rigor and reproducibility, recipients must make all data available to the broad scientific community via the NIA-supported AD Knowledge Portal, or through other NIH-designated data repositories, and/or open-source/open-access platforms adopting the FAIR principles.

In keeping with the open science aspect of this funding initiative, all data sets used/generated on the project (such as data about phenotypes and high-dimensional omic data, including genomic, proteomic, and metabolomic data generated from cell-based and animal models) will be made accessible and reusable by qualified individuals other than the original data generators to enable multiple parallel approaches to data analysis and interpretation.

As part of a complete Data Management and Sharing plan, applications must provide a plan and timeline for data generation, reporting and deposition. Applicants should include appropriate support for annotation and curation of the molecular and phenotype data used and/or generated on the project to maximize the usability of the data by the broader research community. Program staff may negotiate modifications to the plan prior to funding.

All data and results generated from animal model studies, including both negative and positive findings, are expected to be incorporated in NIA's Alzheimer's Disease Preclinical Efficacy Database Portal (AlzPED) no later than 9 months after study completion or at the time of first manuscript publication, whichever comes first. Published studies will be incorporated in AlzPED as a curated record; unpublished studies will be incorporated in AlzPED as a citable pre-print.

Recipients will be expected to have all data and analytical results deposited in the AD Knowledge Portal and/or other NIH-designated data repositories after they have undergone basic quality control (within 3 months of data generation completion). Data shared via the AD Knowledge Portal will be made broadly available twice a year and no later than 6 months after deposition.  There will be no publication embargo imposed on the use of data after they have been made available through the AD Knowledge Portal or other data repositories.

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.

Foreign Organizations

Foreign (non-U.S.) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the How to Apply- Application Guide.

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.

In order to expedite review, applicants are requested to notify the NIA Referral Office by email at [email protected] when the application has been submitted. Please include the FON and title, PD/PI name, and title of the application.

Requests of $500,000 or more for direct costs in any year 

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.

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

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

Post Submission Materials

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

Any instructions provided here are in addition to the instructions 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.

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 NIA, 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.
• Compliance with open-science, open-source principles and adherence to NIH guidelines for rigorous study design and transparent reporting, in compliance with NIH guidance on rigor and reproducibility.
• Alignment of animal model studies to general ARRIVE guidelines for rigorous animal research.

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.
• If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by the HHS Office for Civil Rights website.
  • HHS recognizes that NIH research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this NOFO.

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

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

Successful recipients under this NOFO agree that:

Where the award funding involves implementing, acquiring, or upgrading health IT for activities by any funded entity, recipients and subrecipient(s) are required to: Use health IT that meets standards and implementation specifications adopted in 45 CFR part 170, Subpart B, if such standards and implementation specifications can support the activity.  Visit https://www.ecfr.gov/current/title-45/subtitle-A/subchapter-D/part-170/subpart-B to learn more.

Where the award funding involves implementing, acquiring, or upgrading health IT for activities by eligible clinicians in ambulatory settings, or hospitals, eligible under Sections 4101, 4102, and 4201 of the HITECH Act, use health IT certified under the ONC Health IT Certification Program if certified technology can support the activity. Visit https://www.healthit.gov/topic/certification-ehrs/certification-health-it to learn more.

Pursuant to the Cybersecurity Act of 2015, Div. N, § 405, Pub. Law 114-113, 6 USC § 1533(d), the HHS Secretary has established a common set of voluntary, consensus-based, and industry-led guidelines, best practices, methodologies, procedures, and processes.

Successful recipients under this NOFO agree that:

When recipients, subrecipients, or third-party entities have:

1. ongoing and consistent access to HHS owned or operated information or operational technology systems; and 
2. receive, maintain, transmit, store, access, exchange, process, or utilize personal identifiable information (PII) or personal health information (PHI) obtained from the awarding HHS agency for the purposes of executing the award.

Recipients shall develop plans and procedures, modeled after the NIST Cybersecurity framework, to protect HHS systems and data. Please refer to NIH Post-Award Monitoring and Reporting for additional information. 

Not Applicable

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

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.

In keeping with NIA’s strategic goal to enable and promote open science practices and Findable, Accessible, Interoperable, and Reusable (FAIR) data practices, and the NIA/NIH goal to enhance transparent reporting and increase research rigor and reproducibility, recipients must make all data available to the broad scientific community via the NIA-supported AD Knowledge Portal, or through other NIH-designated data repositories, and/or open-source/open-access platforms adopting the FAIR principles.

In keeping with the open science aspect of this funding initiative, all data sets used/generated on the project (such as data about phenotypes and high-dimensional omic data, including genomic, proteomic, and metabolomic data generated from cell-based and animal models) will be made accessible and reusable by qualified individuals other than the original data generators to enable multiple parallel approaches to data analysis and interpretation.

As part of a complete Data Management and Sharing plan, applications must provide a plan and timeline for data generation, reporting and deposition. Applicants should include appropriate support for annotation and curation of the molecular and phenotype data used and/or generated on the project to maximize the usability of the data by the broader research community. Program staff may negotiate modifications to the plan prior to funding.

All data and results generated from animal model studies, including both negative and positive findings, are expected to be incorporated in NIA's Alzheimer's Disease Preclinical Efficacy Database Portal (AlzPED) no later than 9 months after study completion or at the time of first manuscript publication, whichever comes first. Published studies will be incorporated in AlzPED as a curated record; unpublished studies will be incorporated in AlzPED as a citable pre-print.

Recipients will be expected to have all data and analytical results deposited in the AD Knowledge Portal and/or other NIH-designated data repositories after they have undergone basic quality control (within 3 months of data generation completion). Data shared via the AD Knowledge Portal will be made broadly available twice a year and no later than 6 months after deposition.  There will be no publication embargo imposed on the use of data after they have been made available through the AD Knowledge Portal or other data repositories.

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]

Nandini Arunkumar, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-496-9350
Email: [email protected]

Ramesh Vemuri, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-402-7700
Email: [email protected]

Jeni Militano
National Institute on Aging (NIA)
Telephone: 301-827-4020
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.