BRAIN Initiative: Next-Generation Devices for Recording and Modulation in the Human Central Nervous System (UG3/UH3 Clinical Trial Optional) | RFA NS 25 021

Frequently Asked Questions (FAQs)

What is this funding opportunity?

This is a National Institutes of Health (NIH) BRAIN Initiative funding opportunity titled "BRAIN Initiative: Next-Generation Devices for Recording and Modulation in the Human Central Nervous System (UG3/UH3 Clinical Trial Optional)." The funding opportunity number is RFA-NS-25-021.

What is the main goal of the program?

The main goal is translational: to move next-generation devices that record from and/or modulate activity in the human central nervous system closer to real clinical use. The program is intended to help teams push promising neurotechnology concepts through practical development steps needed for therapeutic or diagnostic use in neurological or neuromuscular disorders.

What types of technologies are in scope?

Technologies in scope are next-generation devices for recording neural activity and devices for modulating neural activity in the human central nervous system, with a focus on device concepts intended to become clinically plausible therapeutic or diagnostic tools.

Is this opportunity focused on basic research or translational development?

It is focused on translational development rather than open-ended exploratory research. The emphasis is on engineering progress plus the regulatory, safety, and early clinical steps that commonly block the transition from research prototype to clinical evaluation.

What funding mechanism is used?

The opportunity uses a phased cooperative agreement mechanism: UG3/UH3. It is milestone-driven and includes substantial NIH program staff involvement in shaping the project plan and monitoring progress.

What does "UG3/UH3 phased cooperative agreement" mean in this program?

UG3 is the first phase, generally focused on completing specific, well-defined milestones that reduce risk and demonstrate readiness to move into humans (for example, building a clinical prototype and completing non-clinical testing and verification/validation). If UG3 milestones are met, the project may transition to the UH3 phase, which supports a subsequent small clinical study to obtain critical human data needed for device decisions.

What does "Clinical Trial Optional" mean here?

"Clinical Trial Optional" means applicants may propose a project that includes a small clinical study, but a clinical trial is not required in every application. The announcement is designed to support a clinical pathway when a small human study is justified to answer questions that cannot realistically be resolved through bench testing or animal studies.

What kinds of activities are expected in the UG3 phase?

UG3 activities are generally expected to include milestone-based work demonstrating readiness for human evaluation, such as developing and implementing a clinical prototype, completing non-clinical safety and efficacy testing, and conducting design verification and validation.

Is preparing for FDA regulatory steps part of the expected work?

Yes. A major goal in the UG3 phase can be to prepare for and obtain an Investigational Device Exemption (IDE) for a Significant Risk study when applicable, which is commonly required by the FDA when studying invasive or higher-risk devices in human participants.

What is an IDE and why is it mentioned?

An IDE (Investigational Device Exemption) is an FDA pathway typically required for Significant Risk device studies in humans. It is mentioned because the program aims to help teams complete the evidence-generation and development steps needed for regulatory readiness, including IDE preparation when the planned human study requires it.

What happens in the UH3 phase?

If UG3 milestones are met, UH3 supports a small clinical study intended to answer key questions that cannot realistically be resolved through additional bench testing or animal studies. The clinical work is expected to be targeted toward human data needed to finalize device function, feasibility, or design decisions.

Does meeting UG3 milestones guarantee transition to UH3?

The program is structured so that transition to UH3 is dependent on meeting UG3 milestones and decision points. Continued support is typically tied to achieving the negotiated, quantitative milestones established with NIH program staff.

How are milestones used in this program?

This announcement is explicitly milestone-driven. Applicants should expect a negotiated set of clear, quantitative milestones and decision points, and NIH staff will actively monitor progress. Funding continuation is typically linked to milestone achievement.

How involved will NIH be during the project?

Because this is a cooperative agreement, NIH program staff are expected to take an active role. They may help shape the final project plan before award and will monitor progress after funding starts, with emphasis on meeting agreed milestones and translational deliverables.

Who is eligible to apply?

Eligibility is broad across U.S.-based organizations, including public and private institutions of higher education, nonprofits (with or without 501(c)(3) status), for-profit organizations (other than small businesses), small businesses, and various units of government (state, county, city/township, special districts), as well as independent school districts and public housing authorities/Indian housing authorities.

Are minority-serving institutions and community-based organizations eligible?

Yes. The announcement explicitly includes eligibility for organizations such as HBCUs, Hispanic-serving institutions, Tribally Controlled Colleges and Universities, Alaska Native and Native Hawaiian Serving Institutions, and AANAPISI organizations, as well as faith-based or community-based organizations.

Are foreign (non-U.S.) organizations eligible to apply?

No. Non-U.S. (foreign) organizations are not eligible to apply, and non-domestic components of U.S. organizations are not eligible to apply.

Can a U.S. applicant include any work performed outside the United States?

Yes, "foreign components" (as defined by NIH policy) are allowed. This generally means a U.S. applicant may include discrete elements performed outside the U.S. if they meet NIH requirements and are well-justified.

What kinds of disorders is this program aiming to impact?

The program targets devices intended for neurological or neuromuscular disorders, with the aim of developing therapeutic or diagnostic tools suitable for early clinical evaluation.

What is the application deadline listed in the provided information?

The original closing date listed is 2026-09-28.

When was this opportunity created?

The opportunity was created on 2024-11-05.

What is the sponsoring agency?

The sponsoring agency is the National Institutes of Health (NIH).

Where does this opportunity appear in NIH assistance listings?

The provided information references multiple NIH health-related assistance listings (CFDA numbers): 93.173, 93.213, 93.242, 93.273, 93.279, 93.286, 93.853, 93.865, 93.866, and 93.867.

Is the award ceiling or number of awards known from the provided information?

No. The award ceiling and expected number of awards are not specified in the provided data. Applicants would typically need to consult the full FOA text for budget guidance, project period expectations, and any caps or constraints.

What kind of clinical study does the program envision (if included)?

The program emphasizes a small, targeted clinical study in the UH3 phase, focused on obtaining human data needed to finalize device function, feasibility, or design decisions, especially for novel use cases where human data are necessary.

What is the key distinguishing feature of this FOA compared with less structured research grants?

A defining feature is the milestone-driven cooperative agreement structure with active NIH involvement. The intent is to keep projects tightly focused on translational deliverables needed for regulatory readiness and early human evaluation, rather than open-ended exploratory work.