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

Frequently Asked Questions (FAQs)

1) What is this funding opportunity?

This is an FDA-issued funding opportunity supporting R01 grant applications for efficient and innovative natural history studies in rare diseases and rare conditions where important unmet needs remain. The intent is to generate natural history data that are strong enough to directly support medical product development.

2) What is the official funding opportunity title and number?

The 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 opportunity number is RFA-FD-25-017.

3) Who is the sponsoring agency?

The sponsoring agency is the U.S. Food and Drug Administration (FDA).

4) What type of grant mechanism is being used?

The opportunity supports R01 grant applications and is listed as a discretionary grant with a grant funding instrument.

5) What does "Clinical Trials Optional" mean for this NOFO?

"Clinical Trials Optional" indicates applicants may propose work that includes clinical trial-like elements if appropriate. However, the emphasis is on natural history research rather than interventional efficacy testing.

6) What is the main goal of the funded studies?

The central goal is to generate natural history data that are usable and interpretable for understanding disease progression, defining meaningful clinical outcomes, and reducing uncertainty that slows therapy development.

7) What kinds of knowledge gaps is FDA trying to address?

FDA is looking for studies that fill critical knowledge gaps that block progress in rare disease research and development. Examples described include clarifying how a disease begins and changes over time, identifying differences among patient subgroups, mapping the range of severity and clinical variability, and defining clinically meaningful milestones.

8) What types of outputs or deliverables does FDA appear to expect?

Based on the description, expected outputs include high-quality natural history datasets and insights that can be used for medical product development, such as interpretable descriptions of disease progression and information useful for defining meaningful clinical outcomes.

9) How can natural history studies funded under this NOFO support product development?

The announcement highlights that natural history studies can support discovery or validation of endpoints, development of disease staging systems, and selection of biomarkers or other measures that could serve as drug development tools. FDA also anticipates funded work could enable better trial design, inform dose selection strategies, support endpoint justification, and strengthen the overall evidence base used to evaluate new therapies.

10) Is the focus limited to one rare disease, or can studies span multiple disorders?

The expected impact described is broad. An application can be compelling if it transforms understanding of a specific rare disease, or if it produces insights that apply across multiple rare diseases that share similar underlying biology or pathophysiology.

11) What does FDA mean by "high quality and interpretable data elements"?

The NOFO emphasis 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.

12) Is this opportunity a new program or a reissue?

It is a reissue of an earlier solicitation, referenced as RFA-FD-22-001.

13) What is the award ceiling shown in the notice?

The notice shows an award ceiling of $600,000.

14) When was this opportunity posted, and what is the closing date shown?

The posting (creation) date listed is July 11, 2025. The original closing date is February 8, 2028.

15) How many awards will FDA make?

The source text does not specify the number of expected awards (the field appears present but not populated). Applicants would typically consult the full NOFO for details such as the number of anticipated awards.

16) What is the CFDA/Assistance Listing number?

The CFDA/Assistance Listing number provided is 93.103.

17) What is the listed activity area, and does it limit the science?

The opportunity is tagged to an activity area described as agriculture/consumer protection/food and nutrition. The description notes this reflects FDA program classification rather than limiting the scientific topics to nutrition.

18) Who is eligible to apply?

Eligibility is broad and includes higher education institutions (public/state-controlled and private), nonprofit organizations (with and without 501(c)(3) status), and for-profit organizations (including small businesses and other for-profits).

19) Are government entities eligible?

Yes. Eligible applicants include local governments, counties, cities or townships, special district governments, state governments, U.S. territorial governments, and federal government entities.

20) Are K-12 or housing-related public entities eligible?

Yes. The eligibility list includes independent school districts and public housing authorities/Indian housing authorities.

21) Are tribal entities eligible?

Yes. The eligibility list includes federally recognized tribal governments, non-federally recognized tribal governments, and other Native American tribal organizations.

22) Are faith-based, community-based, or regional organizations eligible?

Yes. Faith-based and community-based organizations and regional organizations are explicitly included.

23) Are non-U.S. (foreign) organizations allowed to apply?

Yes. International participation is allowed. Non-U.S. entities (foreign organizations) are eligible to apply.

24) Can a U.S. organization include non-U.S. components or foreign sites?

Yes. Non-domestic components of U.S. organizations may participate, and foreign components (as defined in the NIH Grants Policy Statement) are permitted.

25) Why does the NOFO emphasize international participation for rare diseases?

The description notes this matters because rare disease patient populations may be geographically dispersed. International sites or partners can be essential for achieving adequate sample sizes, capturing genetic diversity, and observing disease trajectories over time.

26) What types of studies are most aligned with the stated purpose?

Based on the stated purpose, the strongest proposals would be expected to emphasize efficiency, innovation, data quality, and clear relevance to downstream medical product development rather than purely descriptive epidemiology.

27) Does the provided notice include details like project period, budget period, or review criteria?

The source text indicates those details are not specified there and suggests applicants typically consult the full NOFO for items such as budget period, project period, review criteria, and the number of expected awards.

28) What is the ultimate impact FDA is looking for?

The ultimate endpoint highlighted is facilitating rare disease product development by removing major barriers that hold the field back, either through transforming understanding of a specific rare disease or producing a framework and insights that can be leveraged across related disorders.