Multi-disciplinary Machine-assisted, Genomic Analysis and Clinical Approaches to Shortening the Rare Diseases Diagnostic Odyssey (UG3/UH3 Clinical Trial Not Allowed) | RFA TR 20 030

Opportunity Information: Apply for RFA TR 20 030

This NIH funding opportunity (RFA-TR-20-030) supports the development of new, multidisciplinary diagnostic strategies aimed at shortening the "diagnostic odyssey" experienced by people with rare diseases. The central idea is to bring together machine-assisted methods (such as computational decision support or algorithmic phenotype matching), genomic analysis (for example, sequencing-based approaches and variant interpretation), and clinical consultation into practical diagnostic workflows. The emphasis is not simply on creating sophisticated tools for specialty centers, but on designing approaches that can realistically be adopted by front-line clinicians in primary care or secondary care settings. In other words, the work needs to translate into something that fits into everyday clinical practice, can be integrated into standard workflows, and can help providers recognize and diagnose rare diseases earlier and more reliably.

The award uses a cooperative agreement mechanism (UG3/UH3), which typically reflects a milestone-driven, phased approach where early development and feasibility work transitions into a later implementation or expansion phase, with substantial programmatic involvement from NIH. The activity category is health, and the associated CFDA number is 93.350. The FOA is explicitly labeled "Clinical Trial Not Allowed," meaning the proposed research cannot be structured as a clinical trial as defined by NIH policy. Applicants can still do rigorous clinical research and evaluation, but they must avoid study designs that meet NIH's definition of a clinical trial (for example, prospective assignment to an intervention to assess health-related outcomes). In practice, this often steers projects toward tool development, workflow integration, retrospective analyses, observational validation, clinical decision-support prototyping, and other non-trial evaluation strategies.

From a technical and practical standpoint, the FOA prioritizes diagnostic strategies that combine three pillars: (1) machine assistance, which could include automated extraction of phenotypes from clinical notes, algorithmic triage, probabilistic differential diagnosis systems, or intelligent matching to known rare disease patterns; (2) genomic analysis, such as genome or exome sequencing pipelines, variant prioritization, and interpretation methods that connect genotype to phenotype; and (3) clinical consultation, meaning the approach should incorporate expert input or structured consult pathways in a way that is feasible outside major tertiary centers. A key requirement is implementability at the primary or secondary care level, which implies attention to usability, training burden, time constraints in routine visits, compatibility with electronic health records, and clear outputs that help clinicians decide what to do next (for example, what test to order, when to refer, and how to interpret results). The overarching goal is earlier recognition and diagnosis, reducing time, cost, and patient harm associated with prolonged diagnostic uncertainty.

Eligibility is broad and includes many types of U.S.-based organizations and governments. Eligible applicants listed include state, county, and 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; public housing authorities/Indian housing authorities; Native American tribal organizations other than federally recognized tribal governments; nonprofits with or without 501(c)(3) status (other than institutions of higher education); for-profit organizations other than small businesses; small businesses; and other organizations. The FOA also highlights additional eligible applicant categories such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISI), 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, Indian/Native American tribal governments that are not federally recognized, and U.S. territories or possessions.

At the same time, the FOA places clear limits on foreign participation. Non-domestic (non-U.S.) entities and non-domestic (non-U.S.) institutions are not eligible to apply as applicant organizations, and non-domestic components of U.S. organizations are not eligible to apply. However, "foreign components" as defined by the NIH Grants Policy Statement are allowed, which generally means a U.S. applicant can include certain foreign collaborations or elements when they meet NIH policy requirements and are justified scientifically, even though a foreign institution cannot be the primary applicant.

Administratively, the opportunity was created on 2020-08-28 and had an original closing date of 2020-11-12. It is categorized as discretionary funding, using the cooperative agreement funding instrument type. The provided source data does not specify an award ceiling or the expected number of awards in the excerpt, so those details would ordinarily need to be confirmed in the full FOA document or NIH guide notice. Overall, the program is aimed at accelerating real-world, front-line-ready diagnostic approaches that blend computational tools, genomic testing and interpretation, and clinically grounded consultation pathways, with the practical objective of helping patients with rare diseases reach accurate diagnoses sooner.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Multi-disciplinary Machine-assisted, Genomic Analysis and Clinical Approaches to Shortening the Rare Diseases Diagnostic Odyssey (UG3/UH3 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.
• This funding opportunity was created on 2020-08-28.
• Applicants must submit their applications by 2020-11-12. (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.

Apply for RFA TR 20 030

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