Multi-disciplinary Machine-assisted, Genomic Analysis and Clinical Approaches to Shortening the Rare Diseases Diagnostic Odyssey (UG3/UH3 Clinical Trial Optional) | RFA TR 21 008

Opportunity Information: Apply for RFA TR 21 008

The NIH funding opportunity titled "Multi-disciplinary Machine-assisted, Genomic Analysis and Clinical Approaches to Shortening the Rare Diseases Diagnostic Odyssey (UG3/UH3 Clinical Trial Optional)" (RFA-TR-21-008) supports projects aimed at reducing the long, often frustrating time it takes for many people with rare diseases to receive an accurate diagnosis. The core idea is to fund diagnostic strategies that do not rely solely on highly specialized rare-disease centers, but instead can be used much earlier in the care pathway where most patients actually show up first: primary care and secondary care. The FOA emphasizes practical, workflow-friendly approaches that front-line healthcare providers can adopt without having to completely restructure their clinical operations, with the goal of making advanced diagnostic insight available sooner and more consistently.

A central requirement is that proposed strategies must be multi-disciplinary and combine three main elements: machine-assisted methods (such as algorithmic decision support, automated phenotype extraction, or other computational tools), genomic analysis (for example, sequencing-based testing and variant interpretation approaches), and clinical consultation (meaning expert clinical input that helps translate data into actionable diagnostic direction). In other words, the NIH is looking for integrated diagnostic systems, not isolated tools. Successful applications would typically demonstrate how these components work together in a real clinical setting to improve the speed and accuracy of diagnosis, while also being feasible for everyday clinicians to use.

The award mechanism is a cooperative agreement using the UG3/UH3 structure, which commonly reflects a phased approach. In many NIH programs, UG3 supports an initial milestone-driven planning, feasibility, or early development period, and UH3 supports a subsequent implementation or expansion phase if predefined milestones are met. The announcement notes "Clinical Trial Optional," meaning applicants may propose a clinical trial if it makes sense for evaluating the diagnostic strategy, but a clinical trial is not strictly required. As a cooperative agreement, awardees should also expect substantial NIH involvement compared with a standard grant, typically through programmatic collaboration, milestone oversight, and shared governance expectations.

This is a discretionary health-related funding opportunity under CFDA 93.350 and is administered by the National Institutes of Health. The original application closing date listed for this FOA was April 19, 2021, and the FOA was created on January 15, 2021. The source information provided does not specify an award ceiling or the expected number of awards, so applicants would normally rely on the full FOA text and any associated NIH notices for budget ranges, project periods, and anticipated funding levels.

Eligibility is broad and includes many types of U.S.-based organizations and government entities. Eligible applicants include state, county, city or township governments, special district governments, and independent school districts; public and state-controlled institutions of higher education as well as private institutions of higher education; federally recognized Native American tribal governments, tribal organizations that are not federally recognized, and tribally related housing authorities; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status (as long as they are not institutions of higher education in that classification); for-profit organizations other than small businesses, along with small businesses; and other entities as allowed by NIH policy. The FOA also explicitly highlights additional eligible applicant categories such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, regional organizations, eligible federal agencies, and U.S. territories or possessions.

At the same time, the FOA draws clear boundaries around foreign participation. Non-domestic (non-U.S.) entities and foreign institutions are not eligible to apply as applicants. Non-domestic components of U.S. organizations are also not eligible to apply. However, "foreign components" as defined in the NIH Grants Policy Statement are allowed, which generally means a U.S. applicant may include certain well-justified international elements (such as collaborations, patient cohorts, specialized analyses, or data resources) if they are permitted under NIH rules and are essential to the project. This distinction is important for teams that want to incorporate international expertise or datasets while keeping the primary applicant organization U.S.-based and compliant with NIH eligibility requirements.

Overall, the opportunity is focused on building and testing real-world diagnostic approaches that bring sophisticated computational support, genomic testing/interpretation, and clinical expertise into the places where patients most commonly receive care. The intended impact is to shorten the rare-disease diagnostic odyssey by enabling earlier suspicion, more targeted testing, better interpretation of genomic findings in the context of patient presentation, and smoother integration into routine clinical workflows used by front-line providers.

• 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 Optional)" 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 2021-01-15.
• Applicants must submit their applications by 2021-04-19. (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 21 008

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