BRAIN Initiative: Next-Generation Invasive Devices for Recording and Modulation in the Human Central Nervous System (UG3/UH3 Clinical Trial Optional) | RFA NS 21 023

Frequently Asked Questions (FAQs)

What is this NIH BRAIN Initiative funding opportunity?

This opportunity is the NIH BRAIN Initiative FOA titled "Next-Generation Invasive Devices for Recording and Modulation in the Human Central Nervous System (UG3/UH3 Clinical Trial Optional)" (RFA-NS-21-023). It is designed to move promising invasive neurotechnology closer to real-world use in people by supporting translational work focused on safety, evidence, and practical readiness for clinical use.

What is the main goal of the program?

The central goal is to support translational efforts that advance therapeutic and diagnostic invasive devices for conditions affecting the nervous system or neuromuscular system. The program targets technologies where key questions about performance, function, or final design cannot realistically be answered through additional benchtop testing or animal studies alone.

What kinds of devices or technologies are the focus?

The FOA focuses on next-generation invasive devices for recording and/or modulation in the human central nervous system. The intent is to support development paths that can lead to clinically usable devices, including both therapeutic and diagnostic applications.

What stage of development is this FOA intended to support?

This FOA is aimed at the translational stage between an advanced prototype and early clinical experience in humans. It is meant to help teams bridge the gap from academic proof-of-concept toward practical, clinic-ready systems by completing the final major preclinical-to-clinical steps.

What types of activities are supported under this FOA?

Supported activities include building and implementing clinical prototype devices, conducting non-clinical safety and efficacy studies, and completing design verification and validation work that clinical partners and regulators typically expect before human testing.

Does this FOA support regulatory preparation such as FDA submissions?

Yes. The FOA supports the process of obtaining an Investigational Device Exemption (IDE) for a Significant Risk study when applicable, which is a key FDA regulatory pathway for devices that pose potential serious risk and are being studied in humans.

Is a clinical trial required?

No. The FOA is labeled "Clinical Trial Optional," meaning a clinical study may be included when justified, but it is not mandatory. The overall structure emphasizes translation and readiness milestones rather than purely exploratory research.

If a clinical study is included, what is it expected to accomplish?

The FOA anticipates that many projects may culminate in a small clinical study. The purpose is not necessarily to prove definitive clinical benefit, but to generate decision-driving information such as device performance, usability, recording/modulation capabilities, safety signals, and design refinements that are difficult to obtain non-clinically due to novelty or intended use.

What award mechanism is used (UG3/UH3) and what does it mean?

This is a milestone-driven cooperative agreement using the UG3/UH3 phased award mechanism. The UG3 phase is typically an initial, time-limited stage focused on preparatory and risk-reduction activities. If UG3 milestones are met, the project can transition to the UH3 phase, which commonly supports the next stage such as a small clinical study and remaining validation activities.

What kinds of work typically occur during the UG3 phase?

The UG3 phase generally focuses on completing defined preparatory steps such as finalizing the prototype for clinical use, completing required non-clinical testing, establishing manufacturing/quality or reliability processes as needed, and preparing the IDE package.

What kinds of work typically occur during the UH3 phase?

If UG3 milestones are met, the UH3 phase commonly supports executing the next stage of translation. This often includes conducting the small clinical study (when justified) and completing any remaining validation activities needed to support clinical readiness.

What does it mean that this is a cooperative agreement?

A cooperative agreement means NIH program staff are expected to play an active role beyond standard grant administration. This includes negotiating the final project plan before award, agreeing on milestones and go/no-go criteria, and monitoring progress closely to ensure deliverables align with the translational intent of the program.

How important are milestones and go/no-go criteria in this program?

They are central to the FOA. The award is milestone-driven, and progress is closely monitored. Transition from UG3 to UH3 is generally dependent on meeting agreed-upon milestones and go/no-go criteria.

Who is eligible to apply?

Eligibility is broad across many U.S.-based organization types. Eligible applicants include state, county, and local governments; special districts; independent school districts; public and state-controlled colleges and universities; private institutions of higher education; federally recognized tribal governments; tribal organizations that are not federally recognized; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status; for-profit organizations (including small businesses and other-than-small businesses); and other eligible categories.

Are specific institution types explicitly noted as eligible?

Yes. The FOA explicitly notes additional eligible applicant types such as Historically Black Colleges and Universities (HBCUs), Hispanic-serving institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), faith-based or community-based organizations, eligible federal agencies, regional organizations, tribal governments that are not federally recognized, and U.S. territories or possessions.

Are foreign institutions eligible to apply?

No. Foreign institutions are not eligible to apply, and non-U.S. components of U.S. organizations are not eligible to apply.

Are any international elements allowed at all?

Yes. While the applicant organization must be domestic, foreign components (as defined in the NIH Grants Policy Statement) are allowed. This typically means certain discrete international elements may be included when well-justified and compliant with NIH policy.

What is the funding instrument and assistance category?

The funding instrument is a cooperative agreement under a discretionary opportunity category. It falls under health-related federal assistance and is associated with multiple CFDA/assistance listing numbers tied to NIH neuroscience and related programs.

What is the listed award ceiling?

The listed award ceiling is $1,000,000.

What was the referenced closing date for the competition?

The original closing date for the referenced competition was February 20, 2024.

What types of project outcomes is NIH trying to enable through this FOA?

This FOA is best understood as a structured, NIH-partnered pathway intended to help teams complete late-stage preclinical-to-clinical steps, secure regulatory groundwork for a significant risk study when applicable, and generate early human data that meaningfully informs device design and function.

Is this program focused on exploratory research or clinical readiness?

The program is fundamentally structured around translation and readiness milestones. While it can include a clinical study when justified, the emphasis is on advancing toward real-world clinical use, including evidence generation, safety, usability, and practical readiness.