Reissue of RFA-FD-22-001 - Efficient and Innovative Natural History Studies Addressing Unmet Needs in Rare Diseases (R01 Clinical Trials Optional) | RFA FD 25 017

Opportunity Information: Apply for RFA FD 25 017

This funding opportunity, issued by the U.S. Food and Drug Administration (FDA), supports R01 grant applications for efficient and innovative natural history studies in rare diseases and rare conditions where important unmet needs remain. The central goal is to generate natural history data that are strong enough to directly help medical product development, meaning the study outputs should be usable and interpretable for understanding disease progression, defining meaningful clinical outcomes, and reducing uncertainty that slows down therapy development. The NOFO is a reissue of an earlier solicitation (RFA-FD-22-001) and is labeled as "Clinical Trials Optional," which signals that applicants may propose work that includes clinical trial-like elements if appropriate, but the emphasis is on natural history research rather than interventional efficacy testing.

At a practical level, FDA is looking for studies that fill critical knowledge gaps that currently block progress in rare disease research and development. This often includes clarifying how a disease typically begins and changes over time, identifying differences among patient subgroups, mapping the range of severity and clinical variability, and defining milestones that matter clinically. Natural history studies can also support the discovery or validation of endpoints, the development of disease staging systems, and the selection of biomarkers or other measures that could serve as drug development tools. The NOFO stresses "high quality and interpretable data elements," which implies an expectation for rigorous study design, well-defined data standards, consistent measurement approaches, and datasets that can be confidently analyzed and compared across sites and over time.

The expected impact described in the announcement is broad and product-development oriented. FDA anticipates that successful projects will remove major barriers that hold the field back, either by transforming understanding of a specific rare disease or by producing insights that apply across multiple rare diseases that share similar underlying biology or pathophysiology. In other words, an application can be compelling if it focuses deeply on one condition and meaningfully changes what is known, or if it creates a natural history framework that can be leveraged across a family of related disorders. The ultimate endpoint FDA highlights is facilitating rare disease product development, which can include enabling better trial design, informing dose selection strategies, supporting endpoint justification, and improving the overall evidence base used to evaluate new therapies.

The opportunity is listed under the discretionary grant category, with a grant funding instrument and an activity area tagged to agriculture/consumer protection/food and nutrition (reflecting FDA program classification rather than limiting the scientific topics to nutrition). The CFDA/Assistance Listing number provided is 93.103. The opportunity number is RFA-FD-25-017, and the funding opportunity title is "Reissue of RFA-FD-22-001 - Efficient and Innovative Natural History Studies Addressing Unmet Needs in Rare Diseases (R01 Clinical Trials Optional)." The notice shows an award ceiling of $600,000, and the original closing date is February 8, 2028. The posting (creation) date listed is July 11, 2025. The source text does not specify the exact number of expected awards (the field appears present but not populated), so applicants would typically consult the full NOFO for details such as budget period, project period, review criteria, and the number of awards anticipated.

Eligibility is intentionally broad and includes most common research-performing and community-serving entity types. Eligible applicants include higher education institutions (public/state-controlled and private), nonprofit organizations (both with and without 501(c)(3) status), and for-profit organizations (including small businesses and other for-profits). Government entities at multiple levels are eligible as well, including local governments, counties, cities or townships, special district governments, state governments, U.S. territorial governments, and federal government entities. The eligibility list also includes independent school districts, public housing authorities/Indian housing authorities, and a wide range of tribal entities, including federally recognized tribal governments, non-federally recognized tribal governments, and other Native American tribal organizations. Faith-based and community-based organizations and regional organizations are also explicitly included.

International participation is allowed. Non-U.S. entities (foreign organizations) are eligible to apply, and non-domestic components of U.S. organizations may participate. In addition, foreign components, as defined in the NIH Grants Policy Statement, are permitted. This matters for rare diseases in particular because patient populations may be geographically dispersed, and the ability to include international sites or partners can be essential for achieving adequate sample sizes, capturing genetic diversity, and observing disease trajectories over time.

Overall, this NOFO is aimed at building the kind of reliable, well-structured natural history evidence that rare disease stakeholders need but often lack: evidence that describes the disease with enough precision to support regulatory-grade decision-making and to accelerate the development and evaluation of new diagnostics, devices, or therapeutics. The strongest proposals, based on the stated purpose, would be expected to emphasize efficiency, innovation, data quality, and clear relevance to downstream medical product development rather than purely descriptive epidemiology.

• The Food and Drug Administration in the agriculture, consumer protection, food and nutrition sector is offering a public funding opportunity titled "Reissue of RFA-FD-22-001 - Efficient and Innovative Natural History Studies Addressing Unmet Needs in Rare Diseases (R01 Clinical Trials Optional)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.103.
• This funding opportunity was created on 2025-07-11.
• Applicants must submit their applications by 2028-02-08.
• Each selected applicant is eligible to receive up to $600,000.00 in funding.
• Eligible applicants include: Others.

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