NIDDK High Risk Multi-Center Clinical Study Cooperative Agreement (U01 Clinical Trial Not Allowed) | PAR 25 089

Opportunity Information: Apply for PAR 25 089

The NIDDK High Risk Multi-Center Clinical Study Cooperative Agreement (U01 Clinical Trial Not Allowed) opportunity, PAR-25-089, is a National Institutes of Health (NIH) discretionary funding announcement that supports investigator-initiated, hypothesis-driven, multi-center observational research. The main goal is to enable studies that are considered high-risk, meaning the work may involve substantial uncertainty or operational complexity, but could produce valuable advances if successful. Projects must include more than one clinical center and must focus on diseases and conditions that align with the mission of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), which broadly covers areas such as diabetes and other endocrine/metabolic disorders, digestive diseases, nutrition-related conditions, and kidney/urologic/hematologic diseases.

A key boundary of this NOFO is that it is strictly for observational clinical studies and explicitly does not allow clinical trials. In practical terms, the proposed research should be designed to observe and analyze outcomes, associations, biomarkers, natural history, risk factors, patient-reported outcomes, clinical course, or similar non-interventional questions across multiple sites rather than testing an intervention or assigning participants to treatment arms. Because it is a cooperative agreement (U01), awardees should also expect substantial scientific or programmatic involvement from NIH staff compared with a standard research grant, which typically means more active coordination with NIDDK and potentially participation in shared governance, milestones, data-sharing expectations, and multi-center oversight structures.

Another major requirement is that planning work must be finished before submitting a U01 application under this announcement. The NOFO does not support a planning phase, and applicants are not supposed to use the U01 period to develop foundational study elements that should already be in place. That typically includes having core protocols, manuals of procedures, governance and coordination plans, a feasible recruitment and retention strategy across sites, data management and quality control approaches, and readiness to launch the observational study soon after award. If a group is not yet ready and needs time to finalize protocol development, build the multi-site infrastructure, or complete other startup planning activities, NIDDK directs applicants to first consider the separate implementation planning cooperative agreement mechanism, the U34 (referenced as TEMP9971). NIDDK also strongly encourages applicants to consult with NIDDK scientific/research staff before submitting either a U34 or a U01, which can help confirm fit with NIDDK priorities, clarify whether the study is truly non-interventional, and reduce avoidable compliance or scope issues.

Eligibility is broad and includes many domestic organization types across government, academia, nonprofit, and industry. Eligible applicants listed include state, county, city/township, and 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; tribal organizations other than federally recognized tribal governments; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status (excluding institutions of higher education in those categories); for-profit organizations (other than small businesses); small businesses; and other eligible entities. The announcement also highlights additional eligible applicant categories such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, eligible federal government agencies, regional organizations, and U.S. territories or possessions. At the same time, it clearly states that non-domestic (non-U.S.) entities (foreign organizations) are not eligible to apply, and non-domestic components of U.S. organizations are also not eligible to apply under this NOFO, which effectively limits the applicant organization and its participating components to domestic operations.

From an administrative standpoint, the funding instrument is a cooperative agreement, and the activity category is listed under Food and Nutrition, Health, with CFDA number 93.847. The posted original closing date is 2026-11-05, and the opportunity was created on 2025-01-03. The award ceiling and expected number of awards are not specified in the provided source text, so applicants typically need to consult the full NOFO for budget limits, project period expectations, and review considerations. Overall, this opportunity is positioned for research teams that already have a multi-center observational study fully planned and ready to implement, are pursuing a clear hypothesis relevant to NIDDK priorities, and are prepared to operate within the cooperative agreement structure that involves close coordination with NIDDK program staff.

• The National Institutes of Health in the food and nutrition, health sector is offering a public funding opportunity titled "NIDDK High Risk Multi-Center Clinical Study Cooperative Agreement (U01 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): 93.847.
• This funding opportunity was created on 2025-01-03.
• Applicants must submit their applications by 2026-11-05. (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 25 089

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