BRAIN Initiative: Clinical Studies to Advance Next-Generation Invasive Devices for Recording and Modulation in the Human Central Nervous System (UH3 Clinical Trial Optional) | RFA NS 21 024

Frequently Asked Questions (FAQs)

What is this NIH BRAIN Initiative funding opportunity?

This opportunity is the NIH BRAIN Initiative Funding Opportunity Announcement (FOA) titled "Clinical Studies to Advance Next-Generation Invasive Devices for Recording and Modulation in the Human Central Nervous System (UH3 Clinical Trial Optional)" (RFA-NS-21-024). It supports focused, real-world clinical studies intended to advance next-generation invasive neurotechnology for recording from and/or stimulating the human central nervous system.

What is the main purpose of the program?

The main purpose is to push promising invasive neurotechnology from late-stage development into a tightly scoped clinical setting so investigators can collect specific, high-value human evidence that helps refine device function and finalize key design decisions. The emphasis is on producing actionable information that directly shapes the device's final configuration and reduces major unknowns before larger, later-stage trials.

What kinds of devices are in scope?

Devices in scope are invasive technologies designed for recording and/or modulation (stimulation) in the human central nervous system. The FOA is aimed at next-generation devices that are genuinely novel in the device itself and/or its intended use, where remaining questions cannot realistically be answered through bench testing or animal studies.

What types of clinical studies does the FOA support?

The FOA is centered on early, tightly scoped human testing, including studies such as an Early Feasibility Study. It supports small clinical trials designed specifically to learn how the device performs in people, with the goal of informing design decisions and operational parameters rather than running broad confirmatory clinical efficacy trials.

Are clinical trials required?

The FOA is labeled "Clinical Trial Optional" (UH3 Clinical Trial Optional). Based on the program description provided, the central focus is on clinical studies in humans; however, the mechanism is presented as allowing clinical trials but not necessarily requiring them in every case.

What is the key deliverable NIH expects from the clinical study?

The key deliverable is actionable human data about device performance that can be used to refine the device and finalize design decisions. Examples include information that affects operational parameters, safety strategies, usability, recording quality, stimulation performance, and other core elements that determine readiness for later-stage trials and eventual regulatory pathways.

How does this FOA differ from an incremental or routine clinical study?

This FOA is not intended to fund an incremental study that could be completed outside the clinic. NIH is looking for projects where the remaining uncertainties can only be resolved in humans because the device or its intended use is truly novel. The study should answer concrete questions that directly influence the device's design and readiness for subsequent clinical development.

Does the program support Non-Significant Risk (NSR) studies?

Yes. The FOA can support acute or short-term procedures that an Institutional Review Board (IRB) determines are Non-Significant Risk (NSR).

Does the program support Significant Risk (SR) studies and chronic implants?

Yes. The FOA can also support Significant Risk (SR) research, including studies involving chronic implants, as long as the project obtains an Investigational Device Exemption (IDE) from the FDA when required.

When is an FDA Investigational Device Exemption (IDE) relevant?

An IDE is relevant when the proposed study requires it under FDA requirements, particularly in Significant Risk (SR) research. The FOA notes that SR studies are allowable provided an IDE is obtained when required.

What does NIH mean by "final design" in this FOA?

In this FOA, "final design" refers to the device version that could proceed toward later-stage clinical trials with most of the remaining non-clinical verification and validation already in place. The supported study is expected to produce evidence that meaningfully shapes that final configuration and reduces major unknowns.

What kinds of questions should the supported study answer?

The supported study should answer concrete questions that influence device design and readiness, such as how the device performs in humans, which operational parameters should be set, what safety strategies are needed, how usable the system is in a clinical context, how recording quality performs in practice, and how stimulation performance behaves under real-world conditions.

Why does NIH emphasize human testing for this program?

NIH emphasizes human testing because the FOA targets situations where bench testing or animal work cannot realistically resolve the remaining key uncertainties, particularly when the device or its intended use is genuinely novel. The goal is to generate human evidence that cannot be credibly substituted by additional laboratory or animal testing.

How does this opportunity relate to treating disorders or understanding brain function?

The FOA is intended to help move invasive recording and modulation devices toward treating neurological or psychiatric disorders and toward deeper understanding of human brain function by generating clinically relevant human data needed to refine and finalize device designs.

What is the BRAIN Initiative Public-Private Partnership Program (BRAIN PPP), and how does it connect to this FOA?

The FOA ties into the larger BRAIN Initiative Public-Private Partnership Program (BRAIN PPP). Through BRAIN PPP, NIH has established Memoranda of Understanding with device manufacturers who are willing to provide access to invasive recording and modulation devices for well-controlled clinical research, including capabilities that may not yet be market approved.

How can BRAIN PPP help applicants?

BRAIN PPP may reduce barriers for applicants by enabling access to industry-supplied devices that already have safety and utility data. That existing information may support IRB NSR determinations or FDA IDE submissions without requiring a large additional package of non-clinical testing, while still maintaining regulatory and ethical safeguards.

Does this program require using an industry-supplied device through BRAIN PPP?

The information provided indicates that many applicants may be able to use industry-supplied devices through BRAIN PPP, but it does not state that doing so is mandatory. The practical implication described is increased access and reduced barriers, not an explicit requirement.

What funding mechanism is used for this award?

The award uses a cooperative agreement mechanism. This means NIH is expected to have substantial involvement during the project rather than acting only as a passive funder.

Which agency is offering this opportunity?

The agency listed is the National Institutes of Health (NIH), under the NIH BRAIN Initiative.

What is the maximum award amount (award ceiling)?

The award ceiling listed for this opportunity is $1,500,000.

What general activity areas does the opportunity fall under?

The activity is categorized under areas spanning education, health, and social services, and it is associated with multiple CFDA numbers reflecting participation across several NIH institutes and programs aligned with neurotechnology and brain research.

Who is eligible to apply?

Eligibility is broad across U.S.-based organizations. Eligible applicants include state, county, and local governments; public and private institutions of higher education; independent school districts; special district governments; federally recognized tribal governments and other tribal organizations; public housing authorities/Indian housing authorities; nonprofits (with and without 501(c)(3) status); for-profit organizations (other than small businesses); and small businesses.

Are specific institution types explicitly highlighted as eligible?

Yes. The FOA explicitly highlights eligibility for Historically Black Colleges and Universities (HBCUs), Hispanic-serving Institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, and Asian American Native American Pacific Islander Serving Institutions (AANAPISIs). It also notes eligible federal agencies and faith-based or community-based organizations.

Are U.S. territories or possessions eligible?

Yes. U.S. territories or possessions are included as eligible applicants.

Are foreign organizations eligible to apply?

No. Non-U.S. entities (foreign organizations and foreign institutions) are not eligible to apply.

Are non-U.S. components of U.S. organizations eligible?

No. Non-U.S. components of U.S. organizations are not eligible to apply, according to the information provided.

Are any foreign activities allowed at all?

Yes. "Foreign components" as defined under NIH policy are allowed, meaning limited, well-justified parts of the work may be conducted outside the U.S. under the umbrella of a U.S. applicant institution.

What is the original closing date for this opportunity?

The opportunity's original closing date is listed as February 20, 2024.

When was the FOA created?

The FOA was created on May 7, 2021.

What stage of development is this funding meant to support?

This program is described as a translational bridge from late-stage development into focused human clinical testing. It is meant to de-risk and finalize next-generation invasive devices by generating human data that informs final design decisions before moving into larger and more definitive clinical trials.