Orphan Products Natural History Studies Grants Program

Efficient and Innovative Natural History Studies Addressing Unmet Needs in Rare Diseases

Funds natural-history studies that improve preparedness for rare disease trial pathways.

The FDA OOPD Natural History Studies Grants Program, active since 2016, funds well-designed, protocol-driven natural history studies that address critical knowledge gaps in rare disease medical product development. The program operates under the R01 mechanism through NOFO RFA-FD-25-017. Studies must generate high-quality, interpretable data elements that remove major barriers to clinical trial readiness and exert significant impact on one or more rare diseases or conditions with unmet needs. The program supports studies that facilitate the development of safe and effective medical products by building the evidentiary foundation FDA requires before clinical trials can proceed efficiently. The February 10, 2026 receipt date has passed; the next and final receipt date under this NOFO is February 8, 2028.

Eligibility mirrors the Clinical Trials Grants Program: any domestic or foreign, public or private, for-profit or nonprofit entity may apply, with federal agencies explicitly excluded. Studies must be protocol-driven with a clearly articulated product-development rationale — purely observational epidemiological studies without a product development context are unlikely to qualify. The rare disease threshold of fewer than 200,000 U.S. patients applies. Applications are submitted via grants.gov under FOA RFA-FD-25-017.

Competitive proposals for the February 2028 cycle should demonstrate that the proposed natural history study addresses a specific, documented knowledge gap blocking progress toward a clinical trial, that the data elements to be collected are interpretable and directly useful to product developers and regulators, and that the study design is efficient and innovative. Applicants who did not submit in the February 2026 cycle have until February 2028 to develop and refine their study protocols. Engagement with patient advocacy groups and rare disease researchers during protocol design strengthens applications by documenting community-defined research priorities and recruitment feasibility.