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

Since 2014, the Brain Research through Advancing Innovative Neurotechnologies® (BRAIN) Initiative has aimed to accelerate the development and application of innovative neurotechnologies, enabling researchers to produce a new dynamic picture of the brain that reveals how individual cells and complex neural circuits interact in both time and space. It is expected that these advances will ultimately lead to new ways to treat and prevent brain disorders.

As one of several federal agencies involved in the BRAIN Initiative, the National Institutes of Health (NIH)'s contributions to the BRAIN Initiative were initially guided by "BRAIN 2025: A Scientific Vision," a strategic plan that detailed seven high-priority research areas. This plan was updated and enhanced in 2019 by: "The BRAIN Initiative 2.0: From Cells to Circuits, Toward Cures" and "The BRAIN Initiative and Neuroethics: Enabling and Enhancing Neuroscience Advances for Society." This, and other BRAIN Initiative notice of funding opportunities (NOFOs), are based on this vision and issued with input from Advisory Councils of the 10 NIH Institutes and Centers supporting the BRAIN Initiative, as assisted by the NIH BRAIN Multi-Council Working Group and Neuroethics Working Group.

The NIH BRAIN Initiative recognizes innovative ideas that require creativity, broad scientific expertise and experience. There are many benefits that flow from a scientific workforce with broad participation including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, and enhancing public trust. The NIH also encourages businesses to participate in the BRAIN Initiative. It is possible for companies to submit applications directly to BRAIN Initiative program announcements or to collaborate with academic researchers in joint submissions. Small businesses should consider applying to one of the BRAIN Initiative small business NOFOs.

The BRAIN Initiative requires a high level of coordination and sharing between investigators. It is expected that BRAIN Initiative awardees will cooperate and coordinate their activities after awards are made by participating in Program Director/Principal Investigator (PD/PI) meetings and in other activities such as the BRAIN Initiative Biennial Conference. The data sharing expectations for BRAIN Initiative awards can be found at NOT-MH-19-010.

RESEARCH OBJECTIVES AND SCOPE

The Theories, Models and Methods (TMM) program provides support for the development and validation of innovative and rigorous theories, models and methods as tools that will advance a quantitative and predictive understanding of brain function across multiple scales, including behavior. Priority will be given to projects that develop novel capabilities for analyzing, integrating, and interpreting the large-scale, complex data emerging from the BRAIN initiative and related efforts, which includes cell-type specific physiological, anatomical, connectivity, and behavioral data.

Applications to this NOFO should focus on the development of fundamentally new or significantly advanced theories of brain function; mechanistic and/or predictive models of neural circuit activity and behavior grounded in empirical data; and/or novel computational or statistical methods for analyzing neural and behavioral datasets. 

TMM tools for analyzing brain activity must leverage data with cellular and sub-second temporal resolution (e.g., single-unit recordings, cellular imaging, connectomics) OR must integrate information across multiple, clearly defined temporal scales (e.g., from synaptic events to learning). Approaches relying solely on non-invasive, low-resolution signals (e.g., scalp EEG, fMRI BOLD) must be directly integrated with and constrained by cellular/circuit-level data. TMM tools for analyzing behavior must incorporate neural data AND must span multiple relevant temporal scales, capturing dynamics pertinent to the neural processes and behavior under investigation. Proposed experimental work must be limited to model parameter estimation and/or testing the validity of the TMM tools being delivered. 

It is expected that the TMM tools developed under this NOFO will be made widely available to the neuroscience research community for their use and modification. TMM projects are required to collaborate with a cohort of end users to provide user feedback. 

Specific topics of interest include, but are not limited to:

Theories of brain function

Development of predictive, mathematically-grounded theories explaining how behavior arises from neural structure, circuit dynamics, computation, cognition, and environmental variables. Examples include:

• Theories of embodied computation that anchor the neural representation of sensory, cognitive, and motor variables to an individual/animal’s ongoing interactions with the environment through dynamic, moment-to-moment, circular, and iterative processes.
• Theories that bridge multiple scales of spatial organization (e.g., molecular, synaptic, cellular, circuit, systems) and/or temporal dynamics (e.g., milliseconds to lifetimes) to generate testable predictions of brain-behavior links or cognitive function.
• Theories linking circuit dynamics and function to specific properties of cell types or anatomical connections, identifying general rules, scaling principles, and contributions of specific circuit motifs to computation.
• Theories elucidating fundamental computational principles employed by biological neural networks, potentially drawing inspiration from or contrasting with artificial networks, but firmly grounded in biological constraints (e.g., neuronal/synaptic dynamics, connectivity patterns, metabolic limits, specific cell-type properties, learning rules).

Computational models of neural and behavioral dynamics

Development and validation of quantitative models that are mechanistically grounded, interpretable, predictive, and rigorously tested against neural and behavioral data. Examples include:

• Mechanistic, interpretable, and/or predictive models of neural dynamics, circuit function, or brain-behavior links that integrate biological details with computational principles.
• Models that integrate knowledge across multiple levels (e.g., linking behavior to neural population activity and cellular/circuit properties).
• Models of cognitive processing (e.g., sensory coding, decision-making, motor control, learning, memory) that are mechanistically grounded in identified circuit elements and dynamics, make quantitative predictions, and are rigorously tested against neural and behavioral data, potentially under ecologically relevant or challenging conditions (e.g., limited information, dynamic environments).
• Development and analysis of neural-inspired computational architectures or artificial intelligence/machine learning systems explicitly designed to gain novel insights into brain function.

Methods for complex data analysis

Development of novel computational, statistical, and analytical techniques designed to extract key insights from complex, large-scale neuroscience datasets. Examples include:

• Development of innovative and scalable computational/statistical methods for dimensionality reduction, identifying latent structure, disentangling contributing factors (e.g., sensory, motor, cognitive, state variables), extracting key dynamical features, or characterizing information flow within large, complex neural and behavioral datasets.
• Novel approaches for principled data fusion and assimilation to quantitatively integrate heterogeneous datasets (e.g., linking behavior with multi-regional activity, anatomical connectivity, and cell-type information) to infer new theories of brain function, or to constrain and validate multi-scale computational models.
• Novel statistical/signal processing methods (e.g., component analysis, graphical models, compressed sensing) to track structure in neural data and link to biophysical signals for mechanistic insights across scales.

Applications Not Responsive to this NOFO

Applications deemed to be non-responsive will not proceed to review. The following are considered non-responsive for this NOFO:

• TMM tools for analyzing brain activity that do not leverage data with cellular and sub-second temporal resolution OR that do not explicitly aim to integrate information across multiple, clearly defined temporal scales.
• TMM tools relying solely on non-invasive, low-resolution signals that are not directly integrated with cellular/circuit-level data. 
• TMM tools for analyzing behavior that do not incorporate neural data AND that do not span multiple relevant temporal scales.
• TMM tool development that is not clearly aimed at elucidating or predicting neurobiological mechanisms.
• Proposed experimental work other than model parameter estimation and/or validity testing of the TMM tools being delivered.
• TMM tools, using disease or treatment paradigms, that are not used to understand underlying behavioral and functional brain circuits.

Special Considerations

National Institute on Drug Abuse (NIDA) applicants are strongly encouraged to review the guidelines and adhere to the requirements applicable to their research listed in the Special Considerations for NIDA Funding Opportunities and Awards. Upon award, these considerations will be included in the Notice of Grant Award.

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.

Prior Consultation with IC staff

Applicants are strongly encouraged to consult the Scientific/Research Contact listed in Section VII to discuss the alignment of their proposed work with the goals of this NOFO and the BRAIN Initiative Program.

Resource Sharing

A major goal of the BRAIN initiative is to support the collaborative development and dissemination of resources. Applications are required to provide a Resource Sharing Plan that outlines how the deliverables from the proposed project, except for data, will be shared and disseminated. Resources to address in the Resource Sharing Plan include algorithms, formal theories, models, methods/protocols, software, technology). See Section IV.2 – Resource Sharing Plan, below.

Data sharing is addressed in a separate Data Management and Sharing Plan in compliance with the NIH Data Management and Sharing Policy. See Section IV.2 - Other Plans, below.

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)

Foreign Organizations/ International Collaborations

NIH will no longer issue awards (new, renewal, or non-competing continuation) to domestic or foreign entities that involve foreign subawards/subcontracts. All NIH-funded research involving foreign subawards/subcontracts must be submitted in response to a NOFO that is specifically designated for funded international collaborations. This new requirement was effective, May 1, 2025.

Applications involving foreign subawards/subcontracts submitted in response to this NOFO will be deemed noncompliant and will not be considered for funding. This policy applies to all monetary international collaborations resulting in foreign subawards/subcontracts, however, it does not preclude unfunded international collaborations or foreign components, funding for foreign consultants, or procurement of unique equipment or supplies from foreign vendors.

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.

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.

R&R or Modular Budget

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

The budget should include funds necessary for travel for up to two key personnel to participate in the BRAIN Initiative Biennial Conference.

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:

MAJOR RESEARCH OBJECTIVES AND SCOPE

Applications to this NOFO should focus on the development of fundamentally new or significantly advanced theories of brain function; mechanistic and/or predictive models of neural circuit activity and behavior grounded in empirical data; and/or novel computational or statistical methods for analyzing neural and behavioral datasets.

TMM tools for analyzing brain activity must leverage data with cellular and sub-second temporal resolution (e.g., single-unit recordings, cellular imaging, connectomics) OR must integrate information across multiple, clearly defined temporal scales (e.g., from synaptic events to learning). Approaches relying solely on non-invasive, low-resolution signals (e.g., scalp EEG, fMRI BOLD) must be directly integrated with and constrained by cellular/circuit-level data. TMM tools for analyzing behavior must incorporate neural data AND must span multiple relevant temporal scales, capturing dynamics pertinent to the neural processes and behavior under investigation. Proposed experimental work must be limited to model parameter estimation and/or testing the validity of the TMM tools being delivered.

It is expected that the TMM tools developed under this NOFO will be made widely available to the neuroscience research community for their use and modification. TMM projects are required to collaborate with a cohort of end users to provide user feedback.

RESEARCH STRATEGY

• Applicants are required to explicitly state the use case for their proposed analytical tool and describe how it can be generalized to other behavior and/or functional circuits in the brain. 
• The proposed activity must have a clear statement of how the tool could be widely used by the neuroscience community and influence fundamental approaches to understanding neuroscience data with cellular and sub-second temporal resolution OR multiple temporal scales. This statement should clearly articulate the specific theoretical or technical challenge that is being addressed and describe how the proposed tool would assist in understanding underlying neurobiological mechanisms.
• It is expected that projects will require a collaboration of theorists, modelers, data scientists, experimentalists, and end users to develop new analytical tools (including theoretical frameworks, modeling platforms and analysis algorithms) for understanding specific challenges and problems. For each discipline, the roles and contributions of each expert must be explicitly stated and clearly delineated. 
• While experimental data collection under this NOFO must be limited to model parameter estimation and/or validity testing, collaboration with experimentalists is strongly encouraged. It is expected that the end deliverables will be used to inform experimental paradigms, hypotheses, and/or data collection.
• All applicants are required to outline strategies and metrics for the collaborating end user(s) to evaluate the credibility of the proposed theories, models and methods; applicants must also describe how these analytical tools will address the question(s) of interest within the intended domain. Examples of strategies and metrics include: comparing proposed theories with other existing theories; performing verification, validation, uncertainty quantification, sensitivity analysis, and documenting limitations of the proposed models and methods. 
• Under circumstances where it may be impractical to perform verification, validation, uncertainty quantification and/or sensitivity analysis of the proposed analytical tools, applicants are required to substantiate: (1) why it is impractical; and (2) where appropriate, propose alternative methods and metrics that can help build confidence in the analytical tool and/or their predictive capabilities for the intended domain of use.
• Applicants should provide a timeline and personnel effort needed for end user evaluation. The end deliverables for the proposed theories, models or methods should be clearly defined and quantifiable. 
• Applicants should describe the source of the existing data used (e.g., from other investigators, BRAIN Initiative Data Archives, PhysioNet.org, Datadryad.org, CRCNS.org, NIF, NITRC, IEEG, etc.) to develop the proposed analytical tool. 

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.

All applications, regardless of the amount of direct costs requested for any one year, must address a plan for sharing the analytical tools (e.g., theories, models and methods) produced from the proposed project. The plans may include policies for access and sharing; including provisions for appropriate protection of privacy, confidentiality, security, intellectual property, or other rights or requirements.

Resource Sharing Plans for all TMM tools developed under this NOFO must include a section beginning with the heading "Tool Sharing Plan." This plan should provide details for the tool components or modules, tool parameters and associated datasets. The plan should include the minimum requirements for tool documentation, tool building, tool validation and tool reproducibility. Applicants are also expected to include plans to link proposed tools with other relevant tools.

Resource Sharing Plans for TMM tools that include software to instantiate the proposed mathematical or statistical theories, models and methods must also include a section beginning with the heading "Software Sharing Plan." There is no prescribed single license for software produced through grants responding to this announcement. This NOFO, however, includes goals for software dissemination, and requires applicants to include plans for software dissemination plans relative to these goals:

• The software should be freely available to biomedical, biological, behavioral, environmental, and clinical researchers and educators in the non-profit sector, such as institutions of education, research institutions, and government laboratories.
• The terms of software availability should permit the commercialization of enhanced or customized versions of the software, or incorporation of the software or pieces of it into other software packages.
• To preserve utility to the community, the software should be transferable such that another individual or team can reproduce the analytical tool and continue development if the original investigators are unwilling or unable to do so.
• The terms of software availability should include the ability of researchers to modify the source code and to share modifications with other colleagues. In support of this goal, awardees are encouraged to manage and disseminate their source code through an open revision control and source code management system.
• An applicant should take responsibility for creating the original and subsequent official versions of a piece of software, and should provide a plan to manage the dissemination or adoption of improvements or customizations of that software by others. This plan should include a method to distribute other user's contributions such as extensions, compatible modules, or plug-ins.

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. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

Additionally, in accordance with the Notice of Data Sharing Policy for the BRAIN Initiative (NOT-MH-19-010), recipients of BRAIN Initiative awards will be required to share the data they collect using the BRAIN Initiative informatics infrastructure (both data archives and relevant data standards), consistent with authorities under the 21st Century Cures Act and these awards authorized under that Act. All applications to BRAIN Initiative NOFOs must include a Data Management and Sharing Plan. Recipients will be required to coordinate with Program Staff to select appropriate BRAIN Initiative data archives and to submit data to the selected archives every 6 months of the award period. Submitting data to an archive is distinct from sharing that data with the research community. Submitted data will be held in a private enclave until the data are shared with the research community. After the data have been submitted to the appropriate data archive, it will be shared with the research community when papers using the data have been published or at the end of the award period, whichever occurs sooner.

Consistent with authorities under the 21st Century Cures Act, all applications to BRAIN Initiative NOFOs must include a Data Management and Sharing Plan. The BRAIN Initiative data sharing policy (NOT-MH-19-010) establishes the expectation that this plan should include: 

1. A summary of the data that will be shared;
2. A description of the standard(s) that will be used to describe the data;
3. The archive(s) that will house the data; and
4. The proposed timelines for submitting data to the archive and for sharing data with the research community. 

An updated listing of BRAIN Initiative archives is provided at the BRAIN Informatics website. Currently, established archives that may be relevant to this funding opportunity include, but are not limited to: 

1. Distributed Archives for Neurophysiology Data Integration (DANDI; https://www.dandiarchive.org; R24MH117295) for cellular neurophysiology data; 
2. The Neuroscience Multi-omic Data Archive (NeMO; https://nemoarchive.org/about; R24MH114788) for data from -omics experiments; 
3. The Brain Image Library (BIL; https://www.brainimagelibrary.org; R24MH114793) for confocal microscopy data; 
4. Data Archive for the BRAIN Initiative (DABI; https://dabi.loni.usc.edu; R24MH114796) for data related to human invasive device research; 
5. OpenNeuro (https://openneuro.org; R24MH117179) for magnetic resonance imaging and other neuroimaging data; and 
6. Block and Object Storage Service (BossDB; https://bossdb.org; R24MH114785) for electron microscopy and x-ray microtomography data.

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 components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or non-responsive 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:

This NOFO promotes the collaboration of theorists, modelers, data scientists, experimentalists and end users to develop new analytical tools (including theoretical frameworks, modeling platforms and analysis algorithms) for understanding specific challenges and problems. A sound rationale should be provided as to why the approach and the research team are the most appropriate, and likely to generate an exceptionally high impact if successful. The proposed projects are expected to have a level of risk inherent in new and innovative approaches, especially from fields that traditionally fall outside the NIH community.

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 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 on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

• 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.

Additionally, in accordance with the Notice of Data Sharing Policy for the BRAIN Initiative (NOT-MH-19-010), recipients of BRAIN Initiative awards will be required to share the data they collect using the BRAIN Initiative informatics infrastructure (both data archives and relevant data standards), consistent with authorities under the 21st Century Cures Act and these awards authorized under that Act. Recipients will be required to coordinate with Program Staff to select appropriate BRAIN Initiative data archives and to submit data to the selected archives every 6 months of the award period. Submitting data to an archive is distinct from sharing that data with the research community. Submitted data will be held in a private enclave until the data are shared with the research community. After the data have been submitted to the appropriate data archive, it will be shared with the research community when papers using the data have been published or at the end of the award period, whichever occurs sooner.

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]

Jessica Mollick, PhD
National Institute on Drug Abuse (NIDA)
Telephone: 301-827-2949
Email: [email protected]

Email: [email protected]

Chief Grants Management Officer 
National Institute of Drug Abuse (NIDA) 
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.