Prospective Observational Comparative Effectiveness Research in Clinical Neurosciences (UG3/UH3 Clinical Trial Not Allowed) | PAR 22 076

Opportunity Information: Apply for PAR 22 076

This opportunity, titled "Prospective Observational Comparative Effectiveness Research in Clinical Neurosciences (UG3/UH3 Clinical Trial Not Allowed)" (PAR 22-076), is a National Institutes of Health funding announcement from the National Institute of Neurological Disorders and Stroke (NINDS). It supports investigator-initiated studies that compare how well different clinical strategies work in real-world settings, but specifically through prospective observational research rather than clinical trials. In other words, the research is expected to follow people forward in time and collect data as care occurs, without assigning participants to treatments or otherwise running an interventional trial. The overall intent is to generate practical evidence that can meaningfully inform current clinical decision-making in neurology and related neurosciences, while keeping data collection cost-effective and tightly aligned with questions clinicians and health systems face right now.

The research scope is broad as long as it fits NINDS mission and program interests. Applicants can focus on prevention strategies, diagnostic approaches, or comparisons among interventions already used in practice, including drugs, biologics, devices, and procedures, as well as surgical techniques, behavioral approaches, and rehabilitation therapies. The emphasis is on comparative effectiveness: producing evidence about which approach works better for which patients, under which circumstances, and with what trade-offs. Because the studies are observational, applicants are generally expected to leverage routine clinical care pathways, existing health system workflows, registries, pragmatic data capture, and efficient follow-up methods, rather than designing expensive, highly burdensome research infrastructure. The payoff NINDS is looking for is evidence that can change or sharpen clinical practice, guidelines, or real-world care choices, not merely descriptive epidemiology.

The award uses a two-stage UG3/UH3 cooperative agreement structure. The first stage, the UG3 phase, lasts up to two years and functions as a milestone-driven planning and feasibility period. The second stage, the UH3 phase, can support up to five additional years and is intended for conducting the full prospective observational study. A key feature is that the application is submitted as a single, integrated UG3/UH3 package from the start, but the transition from UG3 to UH3 is not automatic. Only projects that meet prespecified scientific milestones and feasibility requirements during UG3 are allowed to move into the UH3 implementation phase. This structure is designed to reduce risk by ensuring that crucial elements like recruitment, data quality, and operational readiness are demonstrated before major resources are committed.

During the UG3 planning phase, NINDS expects both scientific planning and operational planning. Scientific planning can include small-scale data collection specifically aimed at testing feasibility and acceptability, such as whether the proposed data elements can actually be captured reliably, whether patients and sites will participate as expected, and whether the planned analytic approach is realistic given the data that can be obtained. Operational planning is expected to be concrete and practical, including the development of recruitment and retention strategies, case report forms or equivalent data collection instruments, the data management system, and tools and processes for data monitoring and quality management. The intent is that by the end of UG3, the project has a proven, reproducible workflow for identifying eligible participants, collecting high-quality data, keeping participants engaged for follow-up, and managing and analyzing information in a way that supports credible comparative effectiveness conclusions.

The UH3 phase supports execution of the observational study itself, using the finalized protocol and infrastructure established during UG3. Because this is a cooperative agreement, applicants should expect more programmatic involvement from NIH/NINDS than with a standard research project grant, particularly around milestone assessment, study conduct expectations, and accountability for data and quality management. The "Clinical Trial Not Allowed" designation signals that the project must not involve prospective assignment to an intervention or any design features that would make it an NIH-defined clinical trial; the study must remain observational while still being prospective and comparative.

Eligibility is broad and includes a wide range of U.S. and non-U.S. organizations. Eligible applicants listed include state, county, and local governments; special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments and other tribal organizations; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status (outside higher education); for-profit organizations (including other than small businesses); and small businesses. The announcement also highlights additional eligible applicant types such as Historically Black Colleges and Universities (HBCUs), Hispanic-serving Institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISISs), faith-based or community-based organizations, regional organizations, U.S. territories or possessions, eligible federal agencies, and non-domestic (non-U.S.) entities. This wide eligibility reflects the reality that impactful observational CER in neurosciences often depends on diverse clinical settings, community partnerships, and access to varied patient populations.

From an administrative standpoint, the opportunity is categorized as discretionary funding, uses the cooperative agreement funding instrument, and falls under the NIH health activity category with CFDA (now Assistance Listing) number 93.853. The original closing date provided is 2025-05-07. While an award ceiling is not specified in the source text you provided, the staged UG3/UH3 structure implies budgets should be aligned to planning milestones first and then scaled appropriately for the full observational study in UH3, with clear justification tied to recruitment, data systems, and multi-site operations where relevant.

Overall, this FOA is aimed at teams that have a strong, clinically important comparative question in neurological disorders and can credibly show they will collect prospective observational data efficiently, at sufficient quality, and at a scale that makes the results useful for real clinical decisions. The UG3 period is essentially a proving ground for feasibility and infrastructure, and the UH3 period is where the full study is carried out, contingent on meeting the UG3 milestones.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Prospective Observational Comparative Effectiveness Research in Clinical Neurosciences (UG3/UH3 Clinical Trial Not Allowed)" 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 2022-03-21.
• Applicants must submit their applications by 2025-05-07. (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.

Apply for PAR 22 076

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