Prospective Observational Comparative Effectiveness Research in Clinical Neurosciences (UG3/UH3 Clinical Trial Not Allowed)

The National Institute of Neurological Disorders and Stroke (NINDS) invites applications for the **Prospective Observational Comparative Effectiveness Research in Clinical Neurosciences** funding opportunity. This NOFO supports investigator-initiated, prospective observational comparative effectiveness research (CER) studies addressing preventive strategies, diagnostics, or interventions in neuroscience, including drugs, devices, and therapies. The focus is on pragmatic, cost-effective designs reflecting real-world settings. This opportunity does not allow clinical trials and is structured as a UG3/UH3 cooperative agreement with two phases: a planning phase (UG3) of up to two years, followed by an implementation phase (UH3) of up to five years. Transition to the UH3 phase is contingent on achieving UG3 milestones. Applications must address a significant gap in clinical practice and target interventions already used or studied in controlled trials. Studies involving underserved populations, health disparities, and under-researched conditions are especially encouraged. CER studies should justify the selection of interventions, ensure real-world applicability, and provide patient-centered outcomes. Statistical methods for adjusting inherent biases due to non-randomization, such as propensity scoring and regression, must be included. Projects focusing on retrospective analyses, systematic reviews, or meta-analyses are not eligible under this NOFO. Eligible applicants include higher education institutions, nonprofits, for-profits, governments, and foreign entities. Foreign components of U.S. organizations are also eligible. Registrations in SAM.gov, Grants.gov, and eRA Commons are required. The total project period may span up to seven years, including the UG3 and UH3 phases, with budgets not limited but expected to reflect project needs. Applications must be milestone-driven, with a clear plan for addressing real-world challenges, data collection, and stakeholder engagement. Proposals must emphasize real-world effectiveness and stakeholder priorities, including patients, clinicians, and policymakers. Applicants should describe strategies to include diverse populations, handle missing data, and address confounders. For multisite studies, applicants must detail site-specific differences and harmonize outcomes with existing projects using NIH Common Data Elements (CDEs). Collaboration with patient groups and adherence to NIH policies on data management and sharing are required. Key deadlines include an earliest submission date of January 19, 2025, and initial application deadlines on February 19, 2025, for the first cycle. Letters of intent are encouraged 30 days before application submission. Applications must include plans for transitioning from the UG3 to UH3 phase, contingent on achieving milestones reviewed by NIH staff. Awardees will work collaboratively with NINDS scientific staff throughout the project, adhering to cooperative agreement terms and NIH policies. The application review process includes scientific and technical evaluation based on significance, approach, innovation, investigator expertise, and environment. Funding decisions will depend on scientific merit, program priorities, and available funds. For additional information or consultation before applying, contact the scientific or grants management staff listed in the NOFO.