The National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health (NIH), offers the NIH SIREN Neurologic Clinical Trials funding opportunity (Funding Opportunity Number: PAR-25-049). This opportunity invites applications for multi-center clinical trials targeting neurological emergencies and leverages the NIH Strategies to Innovate Emergency Care Clinical Trials Network (SIREN). SIREN enables applicants to efficiently conduct large clinical trials focused on conditions such as traumatic brain injury, status epilepticus, and spinal cord injury, among others, using an established infrastructure of clinical and data coordination centers. These trials should not focus on stroke, as those studies are conducted within the NINDS StrokeNet network. The SIREN network supports emergency trials through collaboration with 14 clinical hubs and satellite sites, and applicants may propose adding additional sites if necessary.

The funding opportunity provides support through a UG3/UH3 cooperative agreement, which involves two phases: an initial UG3 phase, typically lasting one year, followed by a UH3 phase of up to five years upon meeting initial milestones. UG3 support will cover preparation tasks such as finalizing protocols, developing data management tools, and receiving necessary regulatory approvals. The UH3 phase is dedicated to full trial execution, including patient enrollment, follow-up, data collection, and analysis. The NIH provides infrastructure support for SIREN, but applicants must work with the network to develop a project-specific budget that may exceed infrastructure funding, particularly if their project involves complex data management or large sample sizes.

Eligible applicants include public and private institutions of higher education, nonprofit organizations, small businesses, local governments, and certain federal government agencies. Non-U.S. entities and components of U.S. organizations are also eligible. Organizations are required to complete several registrations, including System for Award Management (SAM) and eRA Commons, before applying. Applications proposing projects with a budget exceeding $500,000 in direct costs in any year must consult NINDS program staff at least six weeks before submission.

Applications must include a detailed research strategy that clearly justifies the scientific and clinical need for the proposed intervention, outlines anticipated outcomes, and provides a strong rationale based on preclinical or early clinical data. Trials should focus on pragmatic designs with simple, efficient data collection integrated into standard care, limiting secondary outcomes to those necessary for supporting primary findings. Applications are encouraged from institutions outside the current SIREN network, and applicants are advised to work closely with SIREN’s Clinical Coordinating Center (CCC) and Data Coordinating Center (DCC) for trial planning, statistical analysis, and data management.

Key review criteria include the scientific significance and innovation of the proposed research, feasibility of trial implementation, and the applicant's expertise and available resources. Additional considerations include adherence to informed consent requirements, data and safety monitoring plans, and the adequacy of plans for human subject protection. Applications will be assessed by a Scientific Review Group, followed by secondary review by an Advisory Council, with funding decisions based on scientific merit, funding availability, and alignment with NINDS priorities.

The earliest possible start date for awarded applications is December 2025, with key dates for submission cycles spanning February, June, and October through March 2026. Applicants must ensure alignment with NIH policies, including those for data sharing, and should contact program officials for guidance on compliance and application preparation.