Reissue of RFA-FD-22-001 – Efficient and Innovative Natural History Studies Addressing Unmet Needs in Rare Diseases (R01 Clinical Trials Optional)
🏛 Food and Drug Administration (HHS-FDA)
✓ Free, no account · Source: Grants.gov · Last verified Jul 16, 2026
Can you apply?
This grant is for researchers and institutions studying rare diseases through natural history research that can inform FDA regulatory decisions. Eligible applicants include academic medical centers, research institutions, nonprofit organizations, and small businesses with established research capacity. The program supports observational studies, longitudinal cohorts, and registry-based research that characterizes disease progression, clinical outcomes, and natural history in rare disease populations. Clinical trials are optional but supported. Funding is available to U.S. and foreign institutions, though U.S. entities are prioritized. The grant specifically aims to address knowledge gaps that delay drug development and regulatory approval for rare disease treatments, focusing on studies that generate evidence useful to the FDA and the rare disease community.
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Program description
The purpose of this notice of funding opportunity (NOFO) is to support efficient and innovative natural history studies that advance medical product development in rare diseases/conditions with unmet needs. Through the support of natural history studies with high quality and interpretable data elements, FDA expects to address critical knowledge gaps, remove major barriers to progress in the field, exert a significant and broad impact on a specific rare disease or multiple rare diseases with similar pathophysiology, and facilitate rare disease product development.
Who can apply
Eligible applicants
How to apply
Application links
Required documents
- NIH/SF-424 (R&R) application form
- Project narrative (specific aims, significance, innovation, approach, timeline)
- Detailed budget and budget justification
- Biosketches of key personnel (NIH format)
- Letters of support from participating institutions, registries, and clinical sites
- Data management and sharing plan
- IRB approval or evidence of institutional review process
- Preliminary data and feasibility documentation
- Letters of commitment from patient advocacy organizations or disease registries
- Research timeline with recruitment and follow-up milestones
Program contact
- 👤 Stephanie Bogan Grantor
- 📧 Kimberly.Pendleton@fda.hhs.gov
- 📞 3018276802
Funding track record
Recent awards under CFDA 93.103 from the last 3 years — real organizations that won funding through this same program.
Top 10 Largest Recent Awards
-
$121,795,918
-
$76,105,626
-
$50,217,964
-
$47,940,304
-
$36,000,000
-
$35,573,997
-
$35,391,995
-
$30,732,300
-
$23,332,999
-
$21,347,288
Top States by Funding
- AZ 3 awards $131.4M
- MD 7 awards $108.7M
- CA 9 awards $106.5M
- VA 5 awards $96.6M
- PA 10 awards $77.4M
Source: USAspending.gov — federal spending transparency. Data covers last 3 years.
Funding history
Annual funding for this program — Federal obligations (CFDA 93.103). How funding has trended year over year.
| 2016 | $170,482,435 | |
| 2017 est. | $208,900,832 | |
| 2018 | $173,077,408 | |
| 2019 | $198,507,896 | |
| 2020 | $212,448,590 | |
| 2021 | $218,918,739 | |
| 2022 est. | $255,910,458 | |
| 2023 est. | $246,894,600 |
FAQ
What types of research are eligible under this grant?
Primarily natural history studies, observational cohorts, and disease registries that characterize rare disease progression and outcomes. Clinical trials are optional but can be included. Registry expansion and data harmonization projects are also supported.
Who can apply for this grant?
Academic institutions, research centers, nonprofit research organizations, small businesses, and medical centers with research capacity. Both U.S. and foreign institutions may apply, though U.S. entities are prioritized.
What is the typical funding range?
R01 grants typically award $250,000–$500,000+ in direct costs annually, though actual amounts vary. This reissue may have specific budget guidance in the funding opportunity announcement.
How competitive is this grant?
Very competitive. FDA research funding is highly selective. Applications must demonstrate scientific rigor, clear clinical impact, and direct relevance to regulatory decision-making or patient outcomes in rare diseases.
When is the application deadline?
The deadline for this reissue is February 8, 2028, with applications opening July 11, 2025. Check the FOA for any rolling deadlines or submission windows.
💡 Tips for applicants
- Emphasize how your natural history data will directly inform FDA regulatory pathways or accelerate rare disease drug development. Show clear unmet evidence gaps.
- Build strong institutional partnerships with patient advocacy groups, disease registries, and clinical sites to ensure robust recruitment and data quality across diverse populations.
- Use standardized, harmonized data definitions and endpoints aligned with FDA guidance documents; this increases scientific credibility and regulatory utility.
- Include a detailed statistical analysis plan upfront and demonstrate feasibility through preliminary data or letters of commitment from participating sites.
- Focus on patient-centered outcomes and long-term follow-up capacity; natural history studies require sustained commitment and strong data management infrastructure to be competitive.
⚠️ Common mistakes
Applications often fail by proposing exploratory or pilot studies that lack sufficient preliminary data or clear scientific rigor. Another common pitfall is failing to articulate how the natural history data will meaningfully advance FDA decision-making or clinical practice—reviewers expect explicit regulatory relevance and clinical impact. Poor data harmonization, incomplete recruitment plans, or insufficient institutional support for long-term follow-up also weaken applications; the FDA prioritizes sustainable, high-quality cohorts over short-term observational efforts.
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