NIH SIREN Neurologic Clinical Trials (UG3/UH3 - Clinical Trial Required)

The NIH SIREN Neurologic Clinical Trials program, under Funding Opportunity Number PAR-25-049, is a reissued cooperative agreement opportunity (UG3/UH3 mechanism) administered by the National Institute of Neurological Disorders and Stroke (NINDS), a component of the National Institutes of Health (NIH), within the U.S. Department of Health and Human Services. This Notice of Funding Opportunity (NOFO) aims to support multi-center clinical trials focused on neurological emergencies such as status epilepticus, traumatic brain and spinal cord injuries, and other acute neurologic conditions. These trials are to be implemented within the Strategies to Innovate EmeRgENcy Care Clinical Trials Network (SIREN), which provides an established infrastructure for conducting large-scale clinical trials in emergency and pre-hospital settings. The funding mechanism is a phased UG3/UH3 cooperative agreement, where the UG3 phase supports the initial development and start-up of the trial, including protocol development, site recruitment, regulatory approvals, and data system planning. Only projects that successfully complete UG3 milestones will transition to the UH3 phase, which supports full-scale implementation and data analysis. Applications must be designed as hypothesis-driven, pragmatic clinical trials with clearly defined primary and secondary outcomes. This NOFO does not support observational studies, registries, or exploratory early-phase studies; only late Phase II or more advanced clinical trials are eligible. The program encourages applicants outside of the existing SIREN network to apply. However, all funded projects must use the SIREN infrastructure, including the Clinical Coordinating Center (CCC), Data Coordinating Center (DCC), and clinical site networks. Applicants must consult with the CCC and DCC in advance to design an appropriate research and statistical plan and to ensure budget alignment. Additional non-SIREN sites may be included with justification, but they must adhere to SIREN’s centralized contracting and IRB processes. Investigators must also engage early with NINDS staff to ensure alignment with program priorities. Budgets for trials are not capped but must reflect the actual needs of the project and adhere to NIH cost principles. A general guideline is that the total cost per subject should not exceed $25,000, including direct and indirect costs. Applications should provide a detailed budget breakdown, especially for per-subject and site-specific costs. Projects proposing costs over this guideline must justify the increase. Additionally, cost-sharing is not required for this program. Applications are accepted three times annually, with current deadlines set for February 7, June 6, and October 7, with subsequent due dates for resubmissions one month later. The earliest submission date is January 7, 2025, and the program will remain open through July 9, 2026. Projects must adhere to the NIH Application Guide, and use of ASSIST, Grants.gov Workspace, or institutional system-to-system submission methods is required. Applicants must register with relevant systems such as SAM.gov, eRA Commons, and Grants.gov before submission. Scientific review is conducted by NINDS peer review panels, with additional review by the NIH Advisory Council. Awards are expected to start approximately four months after review. Funded trials must meet rigorous data collection, safety monitoring, and reporting requirements, including registration and results posting on ClinicalTrials.gov. Final cleaned and de-identified datasets must be submitted to NINDS within one year of primary publication or 18 months after study completion, whichever comes first. NINDS and NHLBI reserve the right to halt studies not meeting milestones or demonstrating feasibility during the UG3 phase.

Engage early with NINDS and SIREN; budget must align with DCC/CCC; use simple, pragmatic trial designs; trials must meet UG3/UH3 milestones