Clinical Trial Readiness for Rare Diseases, Disorders, and Syndromes (R03 Clinical Trial Not Allowed) | PAR 22 100

Opportunity Information: Apply for PAR 22 100

The National Institutes of Health (NIH) funding opportunity titled "Clinical Trial Readiness for Rare Diseases, Disorders, and Syndromes (R03 Clinical Trial Not Allowed)" (Funding Opportunity Number PAR-22-100) supports short, focused clinical research projects that help rare disease programs get ready for future clinical trials, without actually running a clinical trial under this award. The core idea is to tackle practical, high-impact gaps that often slow rare disease development programs down right before the trial stage. NIH is looking for projects that make it easier to move promising therapeutics or diagnostics toward trials efficiently and responsibly, and that improve the odds that those eventual trials will produce clear, interpretable results.

The emphasis is on "clinical trial readiness," meaning work that strengthens the foundations needed to design and execute a good trial later. In practice, this commonly includes developing, refining, and testing biomarkers that can be measured reliably and that track disease biology or treatment response. It also includes developing and evaluating clinical outcome assessment measures, such as clinician-reported outcomes, patient-reported outcomes, performance outcomes, or other endpoints that can serve as meaningful and defensible measures of benefit. Another major area is natural history and disease characterization work: carefully defining how a rare disease presents, how it progresses over time, what the major sources of variability are across patients, and what time windows and milestones matter most. That kind of information is often essential for choosing endpoints, determining trial duration, estimating sample sizes, and selecting the right patient population and inclusion criteria.

Because this is an R03 mechanism, applicants should generally think in terms of discrete, well-scoped projects rather than large multi-year programs. While the announcement does not list an award ceiling or expected number of awards in the provided text, the R03 format typically aligns with smaller budgets and shorter timelines compared to larger NIH grants, and it is usually best suited for tightly defined deliverables (for example, validating a candidate biomarker assay in a small cohort, piloting the feasibility and measurement properties of an outcome measure, or generating key natural history data elements needed to design a later trial).

A key restriction is embedded in the title: "Clinical Trial Not Allowed." That means the funded work should not be an interventional clinical trial that prospectively assigns human participants to receive an experimental treatment to evaluate health outcomes. Instead, the program supports preparatory clinical studies that may involve human participants and clinical data collection, but are aimed at readiness activities such as endpoint development, biomarker qualification groundwork, observational studies, or other clinical research that de-risks and informs subsequent trial planning. The practical takeaway is that applicants should frame their aims around tools, measures, and disease understanding that enable trials, rather than testing an intervention for efficacy.

Eligibility is broad and includes many types of U.S.-based organizations and government entities. Eligible applicants listed in the source include state, county, city or township 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 Native American tribal organizations that are not federally recognized. Nonprofit organizations are eligible whether or not they hold 501(c)(3) status (as long as they are not institutions of higher education), and for-profit organizations are also eligible (excluding small businesses in that category, since small businesses are separately included as eligible). Small businesses are explicitly eligible as well. The FOA also highlights additional eligible applicants 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.

On foreign participation, the rules are specific. Non-domestic (non-U.S.) entities and non-domestic (non-U.S.) institutions are not eligible to apply directly, and non-domestic components of U.S. organizations are not eligible to apply. However, "foreign components" are allowed as defined by the NIH Grants Policy Statement. In other words, a U.S. applicant organization can include certain international elements in the project (for example, a defined collaboration, data collection site, or specialized analysis) if it meets NIH's definition and requirements for a foreign component, but a foreign institution cannot be the applicant organization.

From an administrative standpoint, this is a discretionary grant in the health area, administered by NIH, and is associated with CFDA numbers 93.350 and 93.865. The original closing date shown in the source data is 2023-04-13, and the FOA creation date is 2022-02-03. Applicants considering similar opportunities should verify current deadlines and any updated NIH notices, since submission dates and policies can change through reissues or updates even when the scientific goals remain similar.

Overall, the FOA is best understood as support for the clinical groundwork that makes rare disease trials possible and more likely to succeed: stronger biomarkers, better endpoints, clearer natural history, and better-informed trial designs for candidate therapeutics or diagnostics that are nearing the point where a trial would be the next step.

• The National Institutes of Health in the health, income security and social services sector is offering a public funding opportunity titled "Clinical Trial Readiness for Rare Diseases, Disorders, and Syndromes (R03 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): 93.350, 93.865.
• This funding opportunity was created on 2022-02-03.
• Applicants must submit their applications by 2023-04-13. (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.

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