Awarded activities will facilitate the translation of novel recording and modulation technologies that can be used to treat and/or diagnose central nervous system (CNS) diseases and disorders and to better understand the human CNS, from proof of concept up to the stage of readiness for first in human (FIH) studies. Technologies may incorporate any signal modality (e.g., electrical, optical, magnetic, acoustic) or a combination thereof. Diverse team-based applications that integrate appropriate domains of expertise are encouraged.

Funding Opportunity Number: RFA-NS-24-031. Assistance Listing: 93.173,93.213,93.242,93.273,93.279,93.286,93.853,93.865,93.866,93.867. Funding Instrument: G. Category: ED,HL,ISS. Award Amount: Up to $750K per award.

RFA-NS-24-031: BRAIN Initiative: Preclinical Proof of Concept for Novel Recording and Modulation Technologies in the Human CNS (R18 - 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 Institute of Neurological Disorders and National Eye Institute ( NEI ) National Institute on Alcohol Abuse and Alcoholism ( NIAAA ) National Institute of Biomedical Imaging and Bioengineering ( NIBIB ) 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 ) Funding Opportunity Title BRAIN Initiative: Preclinical Proof of Concept for Novel Recording and Modulation Technologies in the Human CNS (R18 - Clinical Trial Not Allowed) R18 Research Demonstration and Disseminations Projects 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. April 04, 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 Phase 1 Exploratory/Developmental Cooperative Agreement/Exploratory/Developmental Cooperative Agreement Phase II Exploratory/Developmental Cooperative Agreement Phase II See Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s) 93. 853, 93. 286, 93.

213, 93. 242, 93. 173, 93.

867, 93. 279, 93. 865, 93.

866, 93. 273 Funding Opportunity Purpose Awarded activities will facilitate the translation of novel recording and modulation technologies that can be used to treat and/or diagnose central nervous system (CNS) diseases and disorders and to better understand the human CNS, from proof of concept up to the stage of readiness for first in human (FIH) studies.

Technologies may incorporate any signal modality (e.g., electrical, optical, magnetic, acoustic) or a combination thereof Team-based applications that integrate appropriate domains of expertise are encouraged. Open Date (Earliest Submission Date) Letter of Intent Due Date(s) 60 days prior to the application due 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 How to Apply - Application Guide and the NOFO) is required and strictly enforced.

Applicants must read and follow all application instructions in the How to Apply - Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the How to Apply - 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 .

For applications proposing a collaboration with an industry partner, a successful application will be contingent on the applicant's ability to provide the NIH with documentation of company interest in allowing access to the selected device and associated data needed for conducting the proposed non-clinical studies and for filing an investigator-sponsored IDE in order to conduct the proposed exploratory clinical research study (e.g., an executed Collaborative Research Agreements (CRA) or letter from the partner).

Final negotiations need not be completed at the time of submission, but an executed CRA may be required before issuance of grant award. CRA and Confidential Disclosure Agreement templates can be found here: https://braininitiative. nih.

gov/research/neural-recording-and-modulation/public-private-partnerships-program . These templates can be used as common starting points for negotiations of agreements between the device manufacturer, researcher, and research institution.

These agreements have been developed to streamline interactions among the parties and expedite the formation of partnerships to conduct exploratory clinical research by creating a reasonable starting point for negotiations. The NIH recognizes that specific terms and clauses may need to be altered for specific projects by consensus agreement of the two parties.

This Notice of Funding Opportunity (NOFO) is part of a coordinated effort to develop "innovative technologies to understand the human brain and treat its disorders" as recommended in Section III of the BRAIN 2025 Report.

This NOFO seeks applications for the translation of novel recording and modulation technologies in the human central nervous system (CNS), from device proof of concept up to the stage of readiness for first in human (FIH) studies.

The scope of this program, beginning with establishing proof of concept, may include efforts for technology development, optimization and pre-clinical testing that will advance next-generation human CNS recording and/or modulation devices along the translational path up to the stage of readiness for clinical studies.

Proof of concept is the initial exploration phase where the feasibility and viability of an innovative device concept are evaluated. It involves creating a prototype to demonstrate the basic functionality and potential of the idea, often without the full range of features. Applications should propose design-directed development of a new technology and not be hypothesis-driven.

Devices may be non-invasive, minimally invasive, implantable, or a combination thereof . Technologies may incorporate any signal modality such as electrical, optical, magnetic, acoustic, or any combination thereof. Devices may be used in combination with drugs, biologics, and/or small molecules.

Activities that incorporate the ability to synchronize the device with other technologies in real time are strongly encouraged. Examples of activities that are within the scope of this NOFO include, but are not limited to: Demonstrate basic functionality and potential of the idea (i.e., generate proof of concept data). Scaling device features for future human use.

Activities that work towards preparing for future GLP testing or clinical studies for regulatory approvals. Activities to bring the development process under Design Control and Quality Systems processes. Device, software, and firmware design verification and validation activities.

Development of packaging, connectors, surgical tools , and other accessories. Regulatory activities (e.g., pre-submission meetings with FDA). Projects must begin at the device proof of concept stage and have scientifically sound assays to test the device.

It is expected that by the end of the project period, recipients will have validated the technology or approach in vivo and demonstrated a viable pathway to a first in human study. Preclinical activities supported by this NOFO include those that generate preliminary evidence of device safety and effectiveness.

Applicants are encouraged to provide this safety and effectiveness data to the FDA in a pre-submission meeting during the supported project to determine the scope of research needed for a future pilot clinical study. Expected Project Activities: Develop a technology or approach that is on a credible path towards use in humans within 5 years.

Have a plan to continue developing the device after successful completion of the proposed project. "Begin with the end in mind," using design-driven development principles, such as gathering input from stakeholders and manufacturing partners, and safe, consistent, and reliable operation.

Follow FDA guidance for Design Control and Quality Systems processes as appropriate for the proposed device and with respect to data that will be required to obtain regulatory approval for future clinical studies. Provide letters of support from industrial partners, if applicable.

Consider, where appropriate, multi-PD/PI applications that integrate various domains of expertise, including engineering (e.g., biomedical, electrical, mechanical, industrial), computational (e.g., modeling, control theory, and statistical analysis), and scientific. The anatomical target to be affected or measured should be identified (i.e., brain and/or spinal circuit).

There should be supporting data that the device will focally interact with the anatomical target. There should be a clear plan to evaluate the progression and ultimate success of the project. Specifically, projects must have a clear timeline, quantitative benchmarks, and deliverables.

There should be a description of the design practices that will be used to manage the project. There should be a justification of support for all resources and expertise (e.g., manufacturing partner, regulatory consultant, neuroanatomist).

There should be a justification of the budget and duration of the project within context of the maturity upon entry, anticipated maturity upon exit, needed resources, and project risks, in addition to standard criteria. Applications that include the following activities will be considered non-responsive and will be withdrawn and not reviewed: Clinical Trials are not allowed for this NOFO.

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. Delayed onset studies are not responsive and will not be accepted.

Applications that are missing parts 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 Current-State-of-the-Art-Statement 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.

Applicants are strongly encouraged to consult the Scientific/Research Contact listed below to discuss the alignment of their proposed work with the goals of this NOFO and the BRAIN Initiative. 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 provides 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 NINDS and partner components intend to commit an estimated total of $8 million to fund 5-7 awards. Application budgets are not limited but need to reflect the actual needs of the proposed project. Budgets should rarely exceed $750,000 direct costs per year.

The scope of the proposed project should determine the project period. The maximum project period is three years of support. 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 All organizations administering an eligible parent award may apply for a supplement under this NOFO.

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 - Including the NIH Intramural Program 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 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 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 How to Apply - Application Guide is required and strictly enforced.

Applications that are out of compliance with these instructions may be delayed or not accepted for review. Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review. By the date listed in Part 1.

Overview Information , prospective applicants are asked to submit a letter of intent that includes the following information: Descriptive title of proposed activity Name(s), address(es), and telephone number(s) of the PD(s)/PI(s) Names of other key personnel Participating institution(s) Number and title of this funding opportunity The letter of intent should be sent to: 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. Gantt Chart (Required – 1- page max): Applications that exceed this limit or do not include this attachment will be withdrawn. This attachment should be entitled "Gantt.

pdf". Applicants must include a project timeline in the form of a Gantt chart (or similar) that includes all major tasks to be performed during the project. The chart should also include estimated start and completion dates for those tasks.

Needs Assessment (Required – 3 pages max) . This attachment should be entitled "Needs Assessment. pdf".

The needs assessment should establish performance requirements with clear, quantifiable metrics and identify significant issues faced by stakeholders (e.g., patients, clinicians, caregivers, customers), which is a key step in the design control process and will be evaluated for adequacy.

The Needs Assessment should: provide strong, systematic evidence for the most efficient and effective route to addressing an unmet need; critically evaluate primary or secondary data that have been used to identify deficiencies in current capabilities and the origins of the problem or critical barrier; describe the beneficiaries of the proposed work and how their needs have been identified; distinguish "wants" from "needs" and outline the involvement of those who will benefit in the development of a solution; describe how finite resources can best be deployed to develop and disseminate a feasible and applicable solution; and identify any human factors incorporated into the proposed research that optimize usability.

Intellectual Property (IP) Strategy (Required – 3 pages max). This attachment should be entitled "IP Strategy. pdf".

The program strongly encourages the recipients and/or their collaborators to obtain and retain any IP developed around the device during the project period. Applicants are encouraged to prepare this section of the application in consultation with their institution's technology transfer officials, if applicable.

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. Applicants should describe the IP landscape surrounding their device.

Applicants should describe any known constraints that could impede their technology development (e.g., certain restrictions under transfer or sharing agreements, applicants' previous or present IP filings and publications, similar technologies that are under patent protection and/or on the market, etc.) and how these issues could be addressed.

If the applicant proposes using a component or method whose IP is not owned by the applicant's institution, the applicant should address any limitations imposed on the studies or the project (including IP generation) which would impede achieving the goals of the funding program, such as impeding robust licensing opportunities at project completion.

Applicants should include a letter (see Letters of Support) from the entity that owns the IP indicating whether the entity will provide the technology, if there are any limits on the studies that can be performed with that technology, and agreement about public disclosure of results (including negative results), and whether there is an agreement already in place.

If patents pertinent to the device being developed under this application have been filed, the applicant should indicate the details of filing dates, what type of patents are filed, application status, and associated USPTO links, if applicable. Applicants should discuss future IP filing plans.

For a multiple-PD-PI and/or multiple-institution application, applicants should describe how IP will be shared or otherwise managed, and the infrastructure of each institution for bringing the technologies to practical application and for coordinating these efforts (e.g., licensing, managing IP) among the institutions. Team Management Plan (Required – 2 pages max).

NIH strongly encourages applicants to form multidisciplinary teams able to define the overall device development plan to ensure gaps that need to be filled can clearly be defined and addressed during this funding period, to design the details of the plans and experiments, and to execute the research strategy.

An organizational structure that clearly defines the team structure and relationships among the various components should be described in the team management plan and illustrated in an organizational chart.

This plan should also describe the governance and organizational structure of the leadership team and the research project, including communication plans, processes for making decisions on scientific direction, intellectual property, and procedures for resolving conflicts. For publications, policies should be presented that address decisions about what material to publish and the ordering and recognition of authors.

Schematics (Optional – 1 page max): Applications that exceed this limit will be withdrawn. This attachment should be entitled “Schematics. pdf”.

This attachment may include images, photos, drawings, engineering schematics, design specifics, and associated labeling and captions. Other Clinical Study-related Attachments Communications with the IRB (Optional): For projects requiring limited human studies (e.g., usability), applicants may provide official communications with their IRB.

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 Initiative 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: The research strategy must primarily focus on technology development rather than mechanistic, hypothesis-driven research or biological aims.

Applications should propose target and minimum device specifications as a measure of successful progress at the completion of the R18. The device should take a unique approach to target the relevant anatomy while limiting confounds or side effects.

If the proposed device is for the diagnosis and/or treatment of a central nervous system disorder, the investigators should consider the phenotype, physiology, and feasibility of treating the target clinical population in the design of the technology.

While it is expected that research supported by this NOFO may not have fully been designed prior to submitting the application, applicants are nonetheless expected to provide initial target specifications that describe the intended capabilities of the device to be developed. Supporting data may be preliminary (i.e., unpublished). Supporting data should adequately describe the rigor of prior studies.

Applicants should compare their candidate device’s expected capabilities against commercially available technology approved for human use. Target specifications are encouraged to be quantitative (e.g., “prototype survives 32 days under accelerated aging at 80 degrees C with less than 5% degradation in any one operational parameter”).

Quantifiable (e.g., “we will measure how long it survives in accelerated aging”) or subjective (e.g., “our device will survive aging tests”) specifications are significantly less desirable. If a quantitative target specification is a “best guess estimate”, then applicants are encouraged to describe their assumptions and degree of confidence in the planned value.

Applicants should furthermore provide a rationale for each criterion, such as a comparison against the state of the art. Applicants should describe the engineering design principles to be used to manage their projects.

These principles should specify how design requirements will be developed, refined, and validated; how risks and timelines will be managed; how the team will be managed; and how resource allocations will be modified if obstacles are encountered during execution of the project. Details on methods, assumptions, experimental designs, and data analysis plans should be included in the application.

These details should be incorporated into the overall project timeline, which should also be reflected in a Gantt chart. Ultimately, the project timeline should be designed to provide confidence that the device will meet its target specifications, achieve a specific level of maturity at exit, and perform preclinical safety and effectiveness testing to inform, where appropriate, at least one pre-submission meeting with the FDA.

Experiments should be formulated to validate the technology and to demonstrate its capabilities on the bench or preclinically, rather than advancing the state of biological knowledge. Applicants should justify the specific techniques to be utilized for validation and should relate them to the target condition(s) and population(s). Ensure the experimental design is rigorous.

This includes, but is not limited to justification for model systems, endpoints, adequacy of controls and sample sizes, description of statistical analyses, inclusions of measures to reduce bias, and plans for replication, if applicable. A thorough risk analysis should be included.

It is expected that among the analyses, applicants will describe the maturity and limitations of existing components to be integrated into the device, the maturity and limitations of scientific knowledge about the biological mechanistic basis for the treatment, factors that may adversely affect the timeline, and factors that may limit translation into clinical use.

Applicants are encouraged to use a hazard analysis to inform the risk analysis. Applicants are expected to consider barriers to translation, such as regulatory, reimbursement, IP, and commercialization factors.

Applicants should describe the preliminary capabilities and maturity of any device or component to be integrated into the project and describe other resources, technologies, or capabilities to be incorporated into the system design. For each component to be developed within the project, applicants should justify why off-the-shelf components are inadequate.

Applicants should also describe the anticipated plan after conclusion of the grant period, if successful. Any collaborators, consultants, or subcontractors should be identified, no matter when during the conduct of the research activity the proposed interaction occurs.

Describe how the team, including consultants, has already been engaged and a plan as to how they will continue working together over the course of the project (e.g., recurring team meetings, review and report of data across disciplines, decision-making, participate in meetings with NIH, communication, etc.).

If the applicant has any material from a preliminary needs assessment, it should be included in the separate Needs Assessment attachment as a part of your application package, and not in the Research Plan. Current State-of-the-Art Statement : A current state-of-the-art statement must be included as part of the Research Strategy.

Investigators should specifically define the current state of technology as a benchmark against which their proposed new technology or improvements will be measured. Preliminary/feasibility data are not required or expected for early-stage, high-risk projects. However, a sound rationale is required to provide as to why the approach proposed is the most appropriate and likely to generate an exceptionally high impact if successful.

In