BRAIN Initiative: Clinical Studies to Advance Next-Generation Devices for Recording and Modulation in the Human Central Nervous System (UH3 Clinical Trial Optional)

BRAIN Initiative: Clinical Studies to Advance Next-Generation Devices for Recording and Modulation in the Human Central Nervous System (UH3 Clinical Trial Optional) is sponsored by National Institutes of Health. Supports first-in-human or early-stage clinical studies of next-generation devices for recording and/or stimulation in the human central nervous system.

RFA-NS-25-022: BRAIN Initiative: Clinical Studies to Advance Next-Generation Devices for Recording and Modulation in the Human Central Nervous System (UH3 Clinical Trial Optional) 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 Institute of Neurological Disorders and National Eye Institute ( NEI ) National Institute on Alcohol Abuse and Alcoholism ( NIAAA ) Eunice Kennedy Shriver National Institute of Child Health and Human Development ( NICHD ) National Institute on Deafness and Other Communication Disorders ( NIDCD ) National Institute on Drug Abuse ( NIDA ) National Institute of Mental Health ( NIMH ) National Center for Complementary and Integrative Health ( NCCIH ) National Institute of Biomedical Imaging and Bioengineering ( NIBIB ), November 14, 2024 - Participation added ( NOT-EB-24-020 ) Funding Opportunity Title BRAIN Initiative: Clinical Studies to Advance Next-Generation Devices for Recording and Modulation in the Human Central Nervous System (UH3 Clinical Trial Optional) UH3 Exploratory/Developmental Cooperative Agreement Phase II 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. November 14, 2024 - Notice of NIBIB Participation in RFA-NS-25-022: "BRAIN Initiative: Clinical Studies to Advance Next-Generation Devices for Recording and Modulation in the Human Central Nervous System (UH3 Clinical Trial Optional)". See Notice NOT-EB-24-020 .

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 Demonstration and Dissemination Projects Phase 1 Exploratory/Developmental Cooperative Agreement/Exploratory/Developmental Cooperative Agreement Phase II See Section III. 3. Additional Information on Eligibility .

Assistance Listing Number(s) 93. 853, 93. 273, 93.

867, 93. 865, 93. 213, 93.

286, 93. 242, 93. 866, 93.

173, 93. 279, 93. 286 Funding Opportunity Purpose The purpose of this Notice of Funding Opportunity (NOFO) is to encourage investigators to pursue first-in-human or early stage clinical studies for recording and/or stimulating devices to treat central nervous system disorders and better understand the human brain.

Only Significant Risk (SR) studies that require an Investigational Device Exemption (IDE) from the FDA, such as chronic implants, will be supported by this NOFO.

The clinical study is expected to provide data to answer key questions about the function or final design of a device and is expected to provide information about the device function or final design that cannot be practically obtained through additional non-clinical assessments (e.g., bench top or animal studies) due to the novelty of the device or its intended use.

This NOFO is part of a milestone-driven cooperative agreement program and will involve participation of NIH program staff in negotiating the final project plan before award and monitoring of research progress.

As part of the BRAIN Initiative, NIH has initiated a Public-Private Partnership Program (BRAIN PPP) that includes agreements (Memoranda of Understanding, MOU) with a number of device manufacturers willing to make such devices available, including devices and capabilities not yet market approved but appropriate for clinical research.

In general, it is expected that the devices' existing safety and utility data will be sufficient to enable new FDA IDE and IRB approvals without need for significant additional non-clinical data. For more information on the BRAIN PPP, see https://braininitiative. nih.

gov/research/neural-recording-modulation/public-private-partnerships-program . Individuals, institutions, or businesses developing their own devices or that already have established collaborations with device manufacturers are welcome to apply directly to RFA-NS-25-021 or this NOFO.

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 BRAIN Initiative recognizes that teams working together and capitalizing on innovative ideas and distinct technical domains enhance research opportunities and outcomes.

This includes encouraging cross-disciplinary research projects and collaborations among neuroscientists and researchers from fields such as computational biology, physics, engineering, mathematics, computer and data sciences, as well as bioethics. The NIH 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 .

NIH BRAIN Initiative Public-Private Partnership Program This Notice of Funding Opportunity (NOFO), along with its companion NOFO ( RFA-NS-25-021 for UG3/UH3 phased awards), allows participation in an NIH BRAIN Initiative Public-Private Partnership Program (BRAIN PPP), which aims to facilitate partnerships between clinical investigators and manufacturers of latest-generation stimulating and/or recording devices that are FDA-designated as Class III (posing significant risk of harm), to conduct clinical research in the CNS.

Through the PPP, the BRAIN Initiative is interested in reducing barriers to negotiating such partnerships and ensuring that new clinical studies leverage manufacturers' existing data. Data demonstrating safety and utility of these devices are very costly to obtain and pose a substantial barrier to research progress.

Types of research the BRAIN Initiative plans to support with these partnerships include: New Significant Risk (SR) clinical studies requiring amendments to existing Investigational Devices Exemptions (IDEs) from the FDA SR clinical studies in which a new IDE would require minimal or no additional non-clinical testing (non-clinical testing is not supported by this NOFO) SR clinical studies in which a new IDE would require significant additional non-clinical testing but leverages existing company device data (these types of studies are not supported by this NOFO).

The central feature of the BRAIN PPP is a set of template research agreements for collaborations between researchers, research institutions, and device manufacturers.

These template agreements were generated with substantial input from industry partners, clinical researchers, the FDA, and representatives from institutional tech-transfer and contracts offices, and refined from input at a workshop held on June 3-4, 2015 (video of the workshop is publicly archived at https://braininitiative. nih. gov/news-events/events/workshop-brain-initiative-program-industry-partnerships-facilitate-early-access .)

and a public feedback from a Request for Information issued in the NIH Guide ( NOT-NS-15-032 ). Through these templates, the NIH aims to lower the barriers to utilizing latest-generation devices for early-stage clinical research and to broaden the knowledge base regarding the mechanisms of action and potential therapeutic possibilities of those devices.

There are three sets of template agreement documents associated with the program, which are available at the following website ( https://braininitiative. nih. gov/research/neural-recording-modulation/public-private-partnerships-program ).

Memoranda of Understanding (MOUs) agreed upon by NIH and device company partners to provide a framework under which the specified proprietary devices and associated support will be provided by these partners to BRAIN PPP awardees.

Template Confidential Disclosure Agreements (CDA) to be signed by researchers to initiate detailed discussions that may require knowledge of proprietary company information relevant to the devices and proposed research. Template Collaborative Research Agreements (CRA) to be used as common starting points for negotiations of agreements between the device manufacturer, researcher, and research institution.

These template agreements may serve as a reasonable starting point for negotiations, but the NIH recognizes that specific terms and clauses may need to be altered for specific projects by consensus agreement of the two parties. Use of the BRAIN PPP is optional. Applicants that have already established formal collaborations with device manufacturers (that are part of the BRAIN PPP or otherwise) are also allowed to apply.

Institutions or businesses that are developing their own devices are also welcome to apply to RFA-NS-24-017 and are not limited to working with companies participating in the BRAIN PPP. Likewise, institutions that have already established formal collaborations with device manufacturers (that are part of the BRAIN PPP or otherwise) are also allowed to apply.

Institutions and businesses that are pursuing translational activities beyond the regulatory activities supported by the UG3 phase of this NOFO are encouraged to apply to PAR-21-282 or its companion funding opportunity PAR-21-315 (or their reissues). A list of devices being offered as part of the BRAIN PPP, along with associated information, can be found at https://braininitiative. nih.

gov/research/neural-recording-and-modulation/public-private-partnerships-program . This NOFO seeks to encourage applicants to pursue milestone-driven first-in-human or early stage clinical investigations of devices with recording and/or stimulation capabilities that both advance clinical diagnostic or therapeutic applications and maximize their scientific research value.

These Significant Risk (SR) clinical studies will require an Investigational Device Exemption (IDE) from the FDA and must aim to diagnose or treat a central nervous system (CNS) disorder and better understand the human brain. Studies seeking to develop technology which address central nervous system diseases and care across the lifespan are highly encouraged.

The incorporation of the ability to synchronize peripheral, ambulatory behavioral data signals in the proposed next generation studies are strongly encouraged. These signals should be synchronized in real-time, but analysis may be done in an online or offline manner.

Data do not have to be stored in the device but may be streamed out, as long as it does not interfere significantly with the naturalistic behavior (i.e., a participant must not be required to carry around a large personal computer with them for synchronization to occur). Data privacy of research participants and confidentiality of the data should also be addressed.

Behavioral signals may be those captured by a phone (GPS, keyboard usage, accelerometer, etc.), a smartwatch, or related peripheral behavioral capture device. This NOFO is related to the recommendations in Section III of the BRAIN 2025 Report and addresses the goal of developing "innovative technologies to understand the human brain and treat its disorders." The recent update to the report, The BRAIN Initiative® 2.

0: From Cells to Circuits, Toward Cures , recommends continuation of these ongoing efforts within BRAIN stating the need for better neurotechnology to “understand and manipulate brain function”.

The leap from animal studies to humans is large, and initial clinical studies are often necessary to address critical scientific questions about the function of a device in human patients and/or inform a final device design suitable for eventual FDA market approval.

Initial demonstrations of novel device function in humans have become increasingly required to encourage the industry and venture capital investment necessary to develop a final safe, reliable, and efficacious device that can be manufactured at scale suitable for regulatory approval, yet at a price point viable for success given the constraints of the commercial markets and insurance reimbursement.

This NOFO will support a small clinical study to answer key questions about the function or final design of devices with recording and/or stimulation capabilities that both advance clinical diagnostic or therapeutic applications and maximize their scientific research value. Projects appropriate for this NOFO must have completed all non-clinical testing necessary to obtain an IDE for an SR clinical study prior to entry.

Only SR studies that require an IDE from the FDA, such as chronic implants, will be supported by this NOFO. The clinical study should provide data to answer key questions about the function or final design of a device.

The clinical study is expected to provide information that cannot be practically obtained through additional non-clinical assessments (e.g., bench top or animal studies) due to the novelty of the device or its intended use yet is critical to enable next-generation diagnostic or therapeutic devices. Projects must obtain the necessary FDA and IRB approvals to conduct the clinical study prior to issuance of grant award.

This NOFO utilizes a UH3 cooperative mechanism. As a cooperative agreement, this NOFO supports milestone-driven projects and involves NIH program staff’s participation in negotiating the final milestone plan before award, monitoring the research progress, and making go/no-go decisions.

The expectations of the program are in line with those of industry regarding the advancement of devices through the developmental and translational pipelines. As such, an inherent rate of attrition is possible within this program. Applicants are strongly advised to contact the Scientific/Research contact listed below prior to submission.

Projects must focus on a single CNS condition that falls within the mission of one of the participating institutes of the BRAIN Initiative.

It is expected that devices used within the scope of this program either: are very close to the 'final system' and manufactured using very close to the same manufacturing process as the device to be marketed or studied in a larger clinical study following the completion of this project; or have received Pre-Submission feedback from the FDA (see https://www. fda.

gov/medical-devices/products-and-medical-procedures/neurological-devices and https://www. youtube. com/watch?

v=u0zPKPLW2mU for helpful resources); or require early feasibility clinical data to inform the final device design or manufacturing processes; or are already approved, but are being used for a novel indication, target, or patient population.

For entry to the program, projects should have: A device for which all non-clinical testing necessary for approval(s) to conduct the proposed clinical study has been completed Identified one or more clinically meaningful device outcome measures based on input from key stakeholders (e.g., clinicians, patients, and caregivers) as well as supporting literature. A compelling case for a successful IDE submission.

All regulatory approvals must be in place prior to issuance of the award. This UH3 will support a small clinical study that will lead to either: A marketing application if only a small clinical study or experience is needed to demonstrate the device is safe and effective; or A larger clinical study that will lead to a marketing application; or Use of the clinical experience to inform device design decisions.

Examples of studies that can be proposed include, but are not limited to: Optimization of the device design with respect to the human functional anatomy. Identification of the most simple, reliable, and cost-effective device configuration for more advanced clinical studies and eventual market approval. Basic proof-of-concept testing in human patients.

Studies of the key physiological variables that may impact the function of the device in humans. Initial assessments of device safety, but only in conjunction with obtaining enabling data about device design or function. F.

Non-Responsive Activities: Applications that include the following activities will be considered non-responsive and will be withdrawn and not reviewed: Applications solely proposing Non-Significant Risk NSR studies. Basic research and studies of disease mechanisms. Research projects that involve any animal studies.

Efforts to develop neurotechnology for study of the fundamental function or physiology of the CNS. Non-clinical testing necessary to support regulatory approval. Delayed-onset clinical studies .

Applications lacking a clinical study protocol synopsis included with the submission. Research projects that employ existing, market approved devices for their labeled uses. Projects focused on augmentation of neural function in healthy individuals.

Development of technologies intended exclusively for implant outside the CNS that do not treat or diagnose CNS disorders or provide knowledge about CNS function, including dorsal root ganglion, peripheral, or cranial nerve modulation for the treatment of peripheral nervous system disorders.

Applications that are missing all required attachments are deemed to be incomplete and will be withdrawn and not reviewed: Include a Needs Assessment as an attachment, as described in Section IV. 2. Include an Intellectual Property (IP) Strategy as an attachment, as described in Section IV.

2. Include a Team Management Plan as an attachment, as described in Section IV. 2.

Include a Gantt chart as an attachment, as described in Section IV. 2. Include a Long-term Care Plan for Patients as an attachment, as described in Section IV.

2. Attachments that exceed the maximum page limits listed for each attachment in Section IV. 2 will be considered non-responsive and will be withdrawn.

Because device development is inherently risky, it is anticipated that there may be attrition as projects move through the process. Applications must propose one or more milestones associated with each objective in each year of the project.

Milestones are goals that measure success and efficacy that will be used for go/no-go decision-making for the project and should have quantitative success criteria associated with them (see below for details). For each milestone, provide details on methods, assumptions, experimental designs, and data analysis plans (if the results are quantitatively measured).

Specify the quantitative criteria for measuring success and the rationale used to develop and justify the quantitative criteria identified. Quantitative criteria should be robust and consistent with the state-of-the-art in the field. The timeline for each milestone should be specified and included on the Gantt chart (described below).

Applicants are encouraged to read examples of milestones ( https://www. ninds. nih.

gov/Funding/Apply-Funding/Application-Support-Library/Devices-Milestones ). NIH program staff will contact the applicant to discuss, negotiate the proposed milestones and any changes suggested prior to funding the application. The final agreed upon and approved milestones will be specified in the Notice of Award (NoA).

Progress towards achievement of the final set of milestones will be evaluated yearly by NIH program staff. Program staff may involve independent consultants or subject matter experts with relevant expertise. If justified, future milestones may be revised based on data and information obtained during the previous project period.

If, based on the progress report, a funded project does not meet the milestones, funding for the project may be discontinued.

In addition to milestones, the decision regarding continued funding will also be based on the overall robustness of the entire data package that adequately allows an interpretation of the results (regardless if they have been captured in the milestones), overall progress, portfolio balance and program priorities, competitive landscape, and availability of funds.

NIH encourages increasing the rigor and reproducibility of observed results. In some cases, conducting additional critical experiments will be important for NIH to have confidence in making a funding decision. H.

Quality and Compliance Requirement The use of the Design Control and Quality Systems processes ( https://www. fda. gov/regulatory-information/search-fda-guidance-documents/design-control-guidance-medical-device-manufacturers ) to the degree specified by the FDA is required.

Intermediate steps in the Design Control process (e.g., design reviews, design verification, design validation, and design transfer activities) where appropriate, and IDE submission should be represented in the annual milestones. NIH recognizes that the degree to which Design Controls and Quality Systems processes are required by the FDA may vary substantially depending on the specific device.

Investigators are encouraged to discuss these issues with the FDA and regulatory consultants prior to submitting an application so the extent to which these processes are required is clearly defined and verifiable in the application. Applicants should consider the Quality System requirements at the IDE stage (i.e., design controls) when preparing their device development activities.

Applicants should consider Guidelines and Policies for Monitoring Clinical Research in the formation of a plan for data and safety monitoring as required by the appropriate IC. I.

Intellectual Property (IP) Since the ultimate goal of this program is to bring new therapeutic and diagnostic devices to the market, the program strongly encourages the awardees and/or their collaborators to obtain and retain any IP developed around the device during the project period (see instructions on attachment or letters to address IP issues in Section IV).

Recipients of awards are encouraged to identify and foster relationships with potential licensing and commercialization partners early in the device development process.

The PD/PI(s) are expected to work closely with technology transfer officials at their institution to ensure that royalty agreements, patent filings, and all other necessary intellectual property arrangements are completed in a timely manner and that commercialization plans are developed and updated over the course of the project.

For rare or ultra-rare diseases where commercialization may be challenging, applicants are encouraged to discuss alternative strategies with Scientific/Research staff to get further guidance. Health for all is the principle underlying the continual process of assuring that all individuals or populations have optimal opportunities to attain the best health possible.

Applying the principle of health for all requires that barriers to promoting good health are removed and resources are allocated among populations and/or communities proportional to their need(s). The National Institute of Neurological Disorders and Stroke (NINDS) is dedicated to addressing neurological health disparities as we work to improve the neurological health for all people.

Despite research advances and improvement of health outcomes overall, health disparities within the US as a whole and within neurological disorders and stroke in particular, persist. Disparities in neurological diseases can not be explained by biological risk factors alone and social determinants of health (SDOH) are increasingly recognized as important drivers of disparities in neurologic disease and outcomes ( NINDS SDOH framework ).

Health disparities in neurological disorders exist across the lifespan. In pediatric populations, neurological health disparities in acute care settings such as the emergency room impact the diagnosis, treatment and long-term health and longevity from childhood through adulthood. K.

Pre-application Consultation As a UH3 cooperative agreement, NIH program staff will be involved in the negotiation and execution of the projects. Applicants are strongly encouraged to consult with NIH program staff when planning an application. Early contact provides an opportunity for staff to provide further guidance on program scope, goals, and developing appropriate milestones.

When possible, applicants should contact program staff at least 12 weeks before a receipt date. See Section VIII. Other Information for award authorities and regulations.

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs. Section II. Award Information Cooperative Agreement: A financial assistance mechanism used when there will be substantial Federal scientific or programmatic involvement.

Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI. 2 for additional information about the substantial involvement for this NOFO.

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. Optional: Accepting applications that either propose or do not propose clinical trial(s).

Need help determining whether you are doing a clinical trial? Funds Available and Anticipated Number of Awards The NIH anticipates providing $10M per year to fund an estimated 5 to 7 awards. Application budgets are not limited but need to reflect the actual needs of the proposed project.

Budgets should rarely exceed $1,500,000 – direct costs per year. The total duration may not exceed 5 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) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply. Foreign components, as defined in the NIH Grants Policy Statement , are allowed. Applicant organizations 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 .

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 registration; 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