NIDDK High Risk Multi-Center Clinical Study Cooperative Agreement (U01 Clinical Trial Not Allowed) | PAR 21 103

Opportunity Information: Apply for PAR 21 103

The NIDDK High Risk Multi-Center Clinical Study Cooperative Agreement (U01 Clinical Trial Not Allowed), Funding Opportunity Number PAR-21-103, is an NIH discretionary funding opportunity that supports investigator-initiated, hypothesis-driven, multi-center observational research. It is designed specifically for studies that involve more than one clinical center and address diseases and conditions that fall within the mission of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), which broadly includes diabetes, endocrinology and metabolic diseases, digestive diseases, nutrition-related research, and kidney, urologic, and hematologic diseases. The emphasis on "high risk" signals that NIDDK is willing to consider ambitious, complex projects that may involve substantial operational challenges, multi-site coordination, and uncertainty in execution, so long as the scientific premise is strong and the potential payoff is meaningful for the field.

This opportunity uses a U01 cooperative agreement mechanism, meaning the award is not a standard grant where the research team operates largely independently. Instead, a cooperative agreement implies substantial programmatic involvement by NIH staff during the conduct of the study. In practical terms, applicants should expect a more collaborative relationship with NIDDK Scientific/Research staff, including input on study milestones, coordination practices, and other aspects that help ensure successful execution across multiple clinical sites. Because of that built-in collaboration model, the announcement strongly encourages applicants to consult with NIDDK staff before submitting an application. That pre-submission communication is not just a courtesy; it can help confirm alignment with NIDDK priorities, clarify whether a proposed design fits the observational focus, and identify common pitfalls in multi-center operational planning.

A key boundary of this FOA is that it is "Clinical Trial Not Allowed." That means the proposed research cannot include an interventional clinical trial as defined by NIH (for example, assigning participants prospectively to an intervention to evaluate effects on health outcomes). The intent here is to fund observational clinical studies, which typically involve measuring exposures, characteristics, biomarkers, behaviors, care patterns, or outcomes without assigning interventions. The studies must also be hypothesis-driven, which distinguishes them from purely descriptive registries or exploratory data collection efforts without a clearly articulated set of testable scientific questions.

Another important feature is that planning activities must be completed before submission and are explicitly not permitted under this FOA. In other words, applicants are expected to arrive with the core multi-site study plan already developed: finalized protocols, operational structures, site coordination approaches, governance, data collection workflows, and similar essentials. If a team is not yet ready to implement and still needs a dedicated planning phase, the FOA points applicants to an implementation planning cooperative agreement (U34; referenced as TEMP9971). This effectively creates a pathway where complex multi-center studies can be planned under a U34 and then, once ready for launch, compete for the U01 implementation support.

Eligibility is broad and includes many types of domestic organizations and governmental entities. Eligible applicants listed include state, county, and city or township governments; special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; Native American tribal governments (federally recognized) and tribal organizations (other than federally recognized tribal governments); public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status (other than institutions of higher education); for-profit organizations (other than small businesses); and small businesses, among others. The FOA also calls out 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 agencies, regional organizations, and U.S. territories or possessions. These inclusions reflect NIH’s intent to support a wide range of capable institutions, including those serving underserved or historically underrepresented communities, which can be particularly relevant for multi-center observational research aiming for representative recruitment and generalizable findings.

At the same time, there are clear restrictions regarding foreign involvement. Non-domestic (non-U.S.) entities (foreign organizations and foreign institutions) are not eligible to apply as applicant organizations, and non-domestic components of U.S. organizations are also not eligible to apply as components. However, "foreign components" as defined in the NIH Grants Policy Statement are allowed, meaning a U.S. applicant organization may, under specific circumstances and with appropriate justification and compliance, include certain foreign-based elements within the overall project structure. This distinction matters for multi-center studies that might involve specialized assays, unique populations, or collaborations that cross borders, but it still keeps the primary applicant and organizational control within the United States.

From an administrative standpoint, this opportunity is listed under the National Institutes of Health with a creation date of December 23, 2020, and an original closing date of January 7, 2024. It is categorized under the activity area "Food and Nutrition, Health" and is associated with CFDA number 93.847. The funding instrument type is a cooperative agreement, consistent with the U01 mechanism and its collaborative oversight model. The source information provided does not specify an award ceiling or expected number of awards, which typically means applicants should consult the full FOA text and NIH standard budget guidance for more detailed expectations on scale, allowable costs, and institute-specific budget considerations.

Overall, PAR-21-103 is best understood as an implementation-focused funding path for teams that already have a well-developed, multi-center observational study ready to run, including established coordination plans and clear, testable hypotheses tied to NIDDK-relevant diseases. The most competitive applications are likely to be those that demonstrate strong scientific rationale, credible multi-site operational readiness, robust data quality and harmonization strategies, and an ability to work effectively within the cooperative agreement framework where NIH staff have an active role in the project’s conduct and success.

• 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 2020-12-23.
• Applicants must submit their applications by 2024-01-07. (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 21 103

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