BRAIN Initiative: Next-Generation Devices for Recording and Modulation in the Human Central Nervous System (UG3/UH3 Clinical Trial Optional)
Funding Agency:
- National Institutes of Health
This Notice of Funding Opportunity (NOFO), along with its companion NOFO (RFA-NS-25-022 for UH3 clinical research applications), allows participation in an NIH BRAIN 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 BRAIN Initiative, NIH 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 NIH plans to support with these partnerships include:
- IRB-approved Non-Significant Risk (NSR) clinical research studies (Note: these types of applications are not covered by this NOFO)
- 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 no or minimal additional non-clinical testing
- SR clinical studies in which a new IDE would require significant additional non-clinical testing but leverages existing company device data (Note: these types of applications are not covered 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 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).
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 supports regulatory activities required to obtain IRB and FDA approval needed to conduct a small clinical study, and the subsequent study itself (e.g., Early Feasibility Study - https://www.fda.gov/regulatory-information/search-fda-guidance-documents/investigational-device-exemptions-ides-early-feasibility-medical-device-clinical-studies-including). All projects must have two phases: UG3 and UH3. The UG3 phase will support regulatory activities necessary to obtain an IDE and IRB approval for an SR clinical study. All projects will start at the UG3 phase. The duration of the UG3 phase must be one year. Only those UG3 phase projects that have acquired the necessary regulatory approvals will transition to the UH3 phase after NIH administrative review. The UH3 phase will support a small clinical study and can last one to four years, however, the total project period (including both the UG3 and UH3 phases) must not exceed five years. Projects for which only a clinical phase is proposed are outside the scope of this funding opportunity and are encouraged to apply to its companion NOFO RFA-NS-25-022.
This NOFO utilizes a UG3/UH3 cooperative agreement mechanism. As a cooperative agreement, this NOFO supports milestone-driven projects and involves NIH program staff’s participation in negotiating the 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.
C. Scope
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 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 trial 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);
- require early feasibility clinical data to inform the final device design or manufacturing processes.
- are already approved, but are being used for a novel indication, target, or patient population.
Application budgets need to reflect the actual needs of the proposed project.
Applicants must not exceed $500,000 in direct costs per year for the UG3 phase and should rarely exceed $1,500,000 direct costs per year for the UH3 phase.
January 28, 2025
Megan Frankowski, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1779
Email: NINDS-Devices@nih.gov