BRAIN Initiative: New Concepts and Early-Stage Research for Recording and Modulation in the Nervous System (R21) (Clinical Trial Not Allowed) is sponsored by National Institutes of Health (NIH). A central goal of the BRAIN Initiative is to understand how electrical and chemical signals code information in neural circuits and give rise to sensations, thoughts, emotions, and actions.

RFA-EY-25-001: BRAIN Initiative: New Concepts and Early-Stage Research for Recording and Modulation in the Nervous System (R21) (Clinical Trial Not Allowed) This funding opportunity was updated to align with agency priorities. Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations National Eye Institute ( NEI ) National Institute on Alcohol Abuse and Alcoholism ( NIAAA ) National Institute on Deafness and Other Communication Disorders ( NIDCD ), December 18, 2024 - Participation added ( NOT-DC-25-021 ) Eunice Kennedy Shriver National Institute of Child Health and Human Development ( NICHD ) National Institute of Mental Health ( NIMH ) National Center for Complementary and Integrative Health ( NCCIH ) National Institute of Neurological Disorders and Stroke ( NINDS ) December 17, 2024 - Participation added ( NOT-NS-25-012 ) National Institute of Biomedical Imaging and Bioengineering ( NIBIB ) December 30, 2024 - Participation added ( NOT-EB-24-021 ) National Institute on Drug Abuse ( NIDA ) January 03, 2025 - Participation added ( NOT-DA-24-064 ) Funding Opportunity Title BRAIN Initiative: New Concepts and Early-Stage Research for Recording and Modulation in the Nervous System (R21) (Clinical Trial Not Allowed) R21 Exploratory/Developmental Research Grant March 31, 2025 - This funding opportunity was updated to align with agency priorities.

Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. January 03, 2025 - Notice of change in "Funding Opportunity Goals" for RFA-EY-25-001 "BRAIN Initiative: New Concepts and Early-Stage Research for Recording and Modulation in the Nervous System (R21) (Clinical Trial Not Allowed)". See Notice NOT-EY-25-004 .

January 03, 2025 - Notice of Change: NIDA Participation in RFA-EY-25-001: BRAIN Initiative: New Concepts and Early-Stage Research for Recording and Modulation in the Nervous System (R21) (Clinical Trial Not Allowed). See Notice NOT-DA-24-064 .

December 30, 2024 - Notice of NIBIB Participation in RFA-EY-25-001: "BRAIN Initiative: New Concepts and Early-Stage Research for Recording and Modulation in the Nervous System (R21) (Clinical Trial Not Allowed)". See Notice NOT-EB-24-021 .

December 18, 2024 - Notice of NIDCD Participation in RFA-EY-25-001, "BRAIN Initiative: New Concepts and Early-Stage Research for Recording and Modulation in the Nervous System (R21) (Clinical Trial Not Allowed)". See Notice NOT-DC-25-021 .

December 17, 2024 - Notice of Change: NINDS Participation in RFA-EY-25-001: BRAIN Initiative: New Concepts and Early-Stage Research for Recording and Modulation in the Nervous System (R21) (Clinical Trial Not Allowed). See Notice NOT-NS-25-012 . April 4, 2024 - Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025.

See Notice NOT-OD-24-084 . August 31, 2022 - Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023. See Notice NOT-OD-22-198 .

August 5, 2022 - Implementation Details for the NIH Data Management and Sharing Policy. See Notice NOT-OD-22-189 . Funding Opportunity Number (FON) Companion Funding Opportunity Research Project (Cooperative Agreements) See Part 2 Section III.

3. Additional Information on Eligibility. Assistance Listing Number(s) 93.

867, 93. 213, 93. 866, 93.

173, 93. 242, 93. 865, 93.

273, 93. 853, 93. 286, 93.

279 Funding Opportunity Purpose This NOFO seeks applications for unique and innovative recording and/or modulation technologies that are in the earliest stage of development, including new and untested ideas that are in the initial stages of conceptualization.

Some projects may aim to increase recording or modulation capabilities by many orders of magnitude, while others may aim to improve the precision and selectivity of recording or modulation (also referred to as stimulation, perturbation, or manipulation). A wide range of modalities are appropriate including acoustic, chemical, electrical, magnetic, and optical, as well as the use of genetic tools.

Invasive or non-invasive approaches are sought that will enable large-scale recording and/or precise manipulation of neural activity, and that would ultimately be compatible with experiments in humans or behaving animals. Applications are encouraged from any qualified individual, including chemists, physicists, engineers, theoreticians, materials scientists, and others from fields not typically involved with neuroscience research.

Funding Opportunity Goal(s) 1) To support eye and vision research projects that address the leading causes of blindness and impaired vision in the U.S. These include retinal diseases; corneal diseases; cataract; glaucoma and optic neuropathies; strabismus; amblyopia; and low vision and blindness rehabilitation.

2) To increase understanding of the normal development and function of the visual system in order to better prevent, diagnose, and treat sight-threatening conditions; and, to enhance the rehabilitation, training, and quality of life of individuals who are partially-sighted or blind.

3) To support a broad program of basic vision research through grants and cooperative agreements; to encourage high quality clinical research, including clinical trials, other epidemiological studies, and health services research; to encourage research training and career development in the sciences related to vision; and to sponsor scientific workshops in high priority research areas to encourage exchange of information among scientists.

Open Date (Earliest Submission Date) Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed 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.

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

Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

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.

Use the NIH ASSIST system to prepare, submit and track your application online. 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. Workspace to prepare and submit your application and eRA Commons to track your application. Part 1.

Overview Information 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 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. 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 annual PI meeting.

The data sharing expectations for BRAIN Initiative awards can be found at NOT-MH-19-010 . This NOFO is related to the recommendations in sections II. 2, II.

3, and II. 4 from the BRAIN 2025 Report . These three recommendations call for accelerated development of new large-scale recording technologies and tools for neural circuit manipulation.

These new technologies and approaches will provide unprecedented opportunities for exploring how the nervous system encodes, processes, utilizes, stores, and retrieves vast quantities of information. A better understanding of this dynamic neural activity will enable researchers to seek new ways to diagnose, treat, and prevent brain disorders.

Achieving these goals requires the ability to record simultaneously from thousands or tens-of- thousands of neurons contributing to the dynamic activity in a neural circuit. The relevant activity may be in clusters of cells packed closely together or may be in widely distributed circuits.

Current microelectrode and imaging technologies are limited in the number of cells from which activity can be isolated and sampled simultaneously, by the size or location of the area to be sampled, by the depth of penetration, and by the invasiveness of the technique that might prohibit their use in human experimentation.

Non-invasive technologies suitable for use in humans are currently limited in spatial resolution and temporal dynamics, as well as in their reflection of on-going electrical activity in circuit elements.

This NOFO seeks entirely new ideas, concepts and/or approaches from physics and engineering, and biology, for how these limitations might be overcome to enable increased recording capabilities on the scale of one or more orders of magnitude beyond that of current technology. This NOFO is also related to the goals of the updated BRAIN 2.

0 Report , which recommends expanding the functionality and integration of electrophysiological and neurochemical methods. The next generation of recording/modulation technology development should include efforts to improve cell-type and neurochemical specificity. Thus, an equally important goal of this NOFO is to discover novel ideas for technology capable of precisely manipulating activity in circuits.

Dissecting the function of neural circuits requires the ability to precisely activate or inactivate brain cells (both neuronal and non-neuronal) in order to investigate underlying mechanisms and demonstrate causality. Current technologies such as microstimulation and optogenetic approaches are limited in specificity, temporal dynamics, and by the invasiveness of the technique.

Applications are expected to propose the development of ideas in the earliest stages for entirely new approaches for neural recording and/or precise manipulation of neural activity. Such ideas could encompass unique and innovative combinations of existing technology that create a synergistic result.

An important goal is to stimulate new thinking and concepts for accelerating development of novel technologies that break current barriers to neural recording and/or manipulation.

In addition to experimental approaches, this NOFO may support early-stage testing using calculations, simulations, computational models, or other mathematical techniques for demonstrating that the signal sources and/or measurement technologies are theoretically capable of meeting future demands.

The support might also be used for building and testing phantoms, prototypes, and in-vitro or other bench-top models, in order to validate underlying theoretical assumptions in preparation for companion NOFOs aimed at proof-of concept testing in animal models.

The technologies that would ultimately evolve from these new approaches should be compatible with experiments in humans and/or behaving animals and should dramatically improve capabilities in order to enable experiments that are currently not possible. Preliminary data are not required; however, they may be included if available.

Applications from individuals not usually associated with neuroscience research or teams that cross boundaries forming interdisciplinary collaborations capable of bringing new and untested ideas are particularly encouraged.

Accordingly, applicants might consider, where appropriate, multi-PD/PI applications that integrate appropriate expertise, including but not limited to biological, chemical, and physical sciences, as well as engineering, computational modeling, and statistics.

Applications Not Responsive to this NOFO The following types of studies are non-responsive to this RFA and will not be reviewed: Research that is not at its earliest stage of development in testing novel technologies intended to reduce barriers to conducting neurobiological experiments.

Projects focused on investigating neurobiological mechanisms, understanding disease, or evaluating therapeutic outcomes, rather than developing technologies and demonstrating their capabilities and potential impact. Studies focused on technologies that are primarily appropriate for the peripheral nervous system rather than the CNS.

Technologies that are not compatible with experiments in behaving animals, or that are focused on development of theoretical models without experimental validation. Projects focused on improving existing methods for noninvasive neuroimaging or neuromodulation (fMRI, TMS, etc.) or other technologies not aimed at recording and modulating CNS activity at cellular or circuit resolution. See Section VIII.

Other Information for award authorities and regulations. Section II. Award Information Grant: A financial assistance mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed The OER Glossary and the How to Apply Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO. Not Allowed: Only accepting applications that do not propose clinical trials.

Need help determining whether you are doing a clinical trial? Funds Available and Anticipated Number of Awards NIH intends to fund an estimated 10 awards per fiscal year, corresponding to a total of $3-4 million in new awards per year. Application budgets may not exceed $400,000 total direct costs over a maximum three-year funding period.

No more than $200,000 in direct costs may be requested in any single year. The scope of the proposed project should determine the project period. The maximum project period is 3 years.

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

Eligibility Information Higher Education Institutions 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 (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Recognized).

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

Eligible Individuals (Program Director/Principal Investigator) Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply-Application Guide. 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 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. All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed. Instructions for Application Submission The following section supplements the instructions found in the How to Apply- Application Guide and should be used for preparing an application to this NOFO.

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. 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 a BRAIN investigator meeting, lasting not more than two days and including up to two overnight stays, for each year of the project.

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.

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions: Research Strategy: The Research Strategy section should identify, where appropriate, the physical principles that will be exploited with the proposed new technology that will theoretically enable substantial improvement in recording and/or modulation of activity suitable for eventual use in humans or behaving animals.

The description should also include, where appropriate, how calculations, simulations, computational models, or other mathematical or bench-top methods will be employed to show feasibility of the novel approach along with the theoretical limitations of the approach in terms of spatial extent, resolution, and temporal dynamics.

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 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. 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: a summary of the data that will be shared; a description of the standard(s) that will be used to describe the data; the archive(s) that will house the data; and the proposed timelines for submitting data to the archive and for sharing data with the research community.

An updated listing of BRAIN Initiative archives can be found at https://braininitiative. nih. gov/brain-programs/informatics .

Currently established archives that may be relevant to this funding opportunity include, but are not limited to: Distributed Archives for Neurophysiology Data Integration (DANDI; https://www. dandiarchive. org ; R24MH117295) for cellular neurophysiology data; The Neuroscience Multi-omic Data Archive (NeMO; https://nemoarchive.

org /about ; R24MH114788) for data from -omics experiments; The Brain Image Library (BIL; https://www. brainimagelibrary. org ; R24MH114793) for confocal microscopy data; Data Archive for the BRAIN Initiative (DABI; https://dabi.

loni. usc. edu ; R24MH114796) for data related to human invasive device research; OpenNeuro ( https://openneuro.

org ; R24MH117179) for magnetic resonance imaging and other neuroimaging data; and 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.

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 (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. All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement . Pre-award costs are allowable only as described in the NIH Grants Policy Statement Section 7.

9. 1 Selected Items of Cost. 7.

Other Submission Requirements and Information Applications must be submitted electronically following the instructions described in the How to Apply - Application Guide . Paper applications will not be accepted. Applicants must complete all required registrations before the application due date.

Section III. Eligibility Information contains information about registration. For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide .

If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII . All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form .

Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this NOFO for information on registration requirements.

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

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

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 Only the review criteria described below will be considered in the review process.

Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system. For this particular announcement, note the following: The R21 exploratory/developmental grant supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research.

An R21 grant application need not have extensive background material or preliminary information. Accordingly, reviewers will emphasize the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data.

Preliminary data are not required for R21 applications; however, they may be included if available. 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.

Factor 1. Importance of the Research (Significance and Innovation) Evaluate the importance of the proposed research in the context of current scientific challenges and opportunities, either for advancing knowledge within the field, or more broadly. Assess whether the application addresses an important gap in knowledge in the field, would solve a critical problem, or create a valuable conceptual or technical advance.

Evaluate the rationale for undertaking the study, the rigor of the scientific background for the work (e.g., prior literature and/or preliminary data) and whether the scientific background justifies the proposed study. Evaluate the extent to which innovation influences the importance of undertaking the proposed