NIH SIREN Neurologic Clinical Trials (UG3/UH3 - Clinical Trial Required) | PAR 25 049

Opportunity Information: Apply for PAR 25 049

The NIH SIREN Neurologic Clinical Trials funding opportunity (PAR-25-049) is a National Institutes of Health cooperative agreement designed to launch and run multi-center clinical trials that address neurologic emergencies. The focus is on time-sensitive, high-acuity neurological conditions where rapid diagnosis and treatment in emergency settings can meaningfully change outcomes. Through this announcement, NIH is looking for investigators with promising interventions or strategies that are ready to be tested in a rigorous, multi-site clinical trial environment, using the established infrastructure of the NIH-funded SIREN Network to accelerate startup, enrollment, and high-quality execution.

A defining feature of this opportunity is that funded trials will be conducted within the NIH SIREN Network rather than built from scratch. Awardees will collaborate closely with two central SIREN components: the SIREN Clinical Coordinating Center (CCC), which helps operationalize and implement the trial efficiently across multiple sites, and the SIREN Data Coordinating Center (DCC), which provides statistical leadership along with data management support. In practice, that means applicants are not only proposing a scientific question and trial design, but are also plugging into an existing system for site coordination, protocol rollout, monitoring, and harmonized data workflows. The SIREN hubs and their affiliated clinical sites are expected to carry out on-the-ground implementation of the clinical protocol, which is particularly important for neurologic emergencies where consistency, speed, and protocol adherence across diverse emergency care settings can make or break a study.

The NOFO uses the UG3/UH3 phased award structure under a cooperative agreement mechanism. In general terms, the UG3 phase supports early-stage trial activities needed to ensure the study is truly ready for full execution (for example, finalizing operational plans, addressing regulatory and IRB needs, refining enrollment workflows, training, and demonstrating readiness milestones). If the UG3 milestones are met, the project can transition to the UH3 phase, where the full multi-center clinical trial is carried out. Because this is a “clinical trial required” announcement, the expectation is that the application will propose an actual interventional clinical trial and include the key elements needed to run it across multiple sites, rather than a purely observational study or preparatory work without an interventional trial component.

The opportunity also draws a clear boundary around stroke-related trials. Multi-center clinical trials in stroke treatment, stroke recovery, or stroke prevention that are supported by NINDS are expected to be run through NIH StrokeNet, not SIREN. In other words, even though stroke is a neurologic emergency, NIH is directing stroke trials into its dedicated stroke trial network, while SIREN is positioned for other neurologic emergencies and related acute-care neurologic conditions that fit SIREN’s mission and infrastructure.

Eligibility is broad and intentionally inclusive. Applicants do not need to already be part of the SIREN infrastructure to apply, which lowers the barrier for new investigators or institutions with strong trial concepts but without established network membership. Eligible applicants include a wide range of U.S. governmental entities (state, county, city/township, special districts), independent school districts, public and state-controlled institutions of higher education, private institutions of higher education, nonprofit organizations with or without 501(c)(3) status, and for-profit organizations (other than small businesses) as well as small businesses. The announcement also explicitly calls out additional eligible groups such as Alaska Native and Native Hawaiian Serving Institutions, AANAPISI institutions, Hispanic-serving institutions, HBCUs, Tribally Controlled Colleges and Universities, tribal governments (including those other than federally recognized), faith-based or community-based organizations, U.S. territories or possessions, regional organizations, eligible federal agencies, and even non-U.S. entities (foreign organizations). This breadth signals NIH’s interest in drawing strong clinical trial proposals from diverse settings and communities, which can be important for enrollment, representativeness, and real-world impact in emergency neurology.

From an administrative standpoint, the opportunity is categorized as discretionary funding, with the funding instrument being a cooperative agreement. Cooperative agreements typically involve substantial scientific and operational involvement from NIH and the network infrastructure, which aligns with the stated roles of the CCC and DCC and the expectation of close coordination across SIREN sites. The activity category is health, and the CFDA number listed is 93.853. The original closing date provided is March 6, 2026, and the opportunity was created on November 7, 2024. The award ceiling and expected number of awards are not specified in the provided summary, so applicants would need to consult the full NOFO for budget limits, project period expectations, milestone requirements, and other submission details.

Overall, this NOFO is best understood as an on-ramp for investigators who have a well-justified, operationally feasible, multi-center clinical trial concept in neurologic emergencies and want to leverage a national emergency neurology research network to run it faster and more consistently than would be possible through independent site-by-site contracting and coordination. The core promise is speed and quality through existing infrastructure, paired with NIH involvement and centralized coordination, with the long-term aim of generating definitive evidence for interventions that could improve outcomes in acute neurologic care.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "NIH SIREN Neurologic Clinical Trials (UG3/UH3 - Clinical Trial Required)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.853.
• This funding opportunity was created on 2024-11-07.
• Applicants must submit their applications by 2026-03-06. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

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