Rare Disease Cohorts in Heart, Lung, Blood and Sleep Disorders (UG3/UH3 Clinical Trial Not Allowed) | RFA HL 20 014

Opportunity Information: Apply for RFA HL 20 014

The NIH funding opportunity titled "Rare Disease Cohorts in Heart, Lung, Blood and Sleep Disorders (UG3/UH3 Clinical Trial Not Allowed)" (RFA-HL-20-014) supports the creation of research centers that build and follow longitudinal patient cohorts for rare diseases affecting the heart, lungs, blood, and sleep (often abbreviated HLBS). The central idea is to fund well-designed observational cohort studies for conditions that affect fewer than 200,000 people in the United States, using epidemiologic approaches that fit the realities of rare diseases, such as small sample sizes, geographic dispersion of patients, and clinical heterogeneity. Rather than supporting interventional trials directly, the program is meant to generate the kind of rigorous natural history, outcomes, and subgroup data that future interventional studies (including clinical trials) can rely on, and to strengthen the evidence base for improved diagnostics and for broader implementation of management guidelines.

A major emphasis of the FOA is deep, modern characterization of rare diseases so that researchers can move beyond broad labels and better explain why patients with what appears to be the same condition can have very different trajectories. Applicants are encouraged to incorporate genetics and deep phenotyping to define disease subtypes, clarify disease mechanisms, and distinguish patients who share a similar physical or morphological presentation but differ by underlying mutation, biology, or risk of complications. The opportunity specifically highlights integrating multiple data streams, including clinical measures, patient-reported outcomes (PROs), laboratory testing, imaging, environmental exposures, and various "-omics" layers, with data science methods that can support complex, multi-dimensional analyses. The expectation is that these cohorts will produce datasets capable of revealing genotype-phenotype relationships, capturing multisystem involvement, and supporting the development of predictive tools that help answer practical questions such as which patients are likely to respond to particular treatments and when intervention might be most beneficial.

The FOA also encourages innovative recruitment and follow-up methods that make rare disease research more inclusive and feasible, recognizing that many patients live far from specialty centers. Telemedicine and other remote participation strategies are explicitly called out as ways to enroll and retain participants who are geographically isolated, reducing access barriers and improving representativeness. Another notable feature is flexibility in how diseases can be grouped for study: investigators are allowed, and in some cases encouraged, to design cohorts that include related rare diseases, disorders, conditions, or syndromes together when they share pathogenesis, affected biochemical or cellular pathways, physiological features, or organ system involvement. The rationale is that studying related conditions side-by-side can accelerate discovery by enabling comparisons across a spectrum of related biology and clinical presentations, and by allowing insights from one disorder to inform another. The FOA gives an example in blood disorders, where a cohort could focus on hemoglobin disorders broadly rather than limiting enrollment to a single diagnosis like sickle cell disease or thalassemia.

From an administrative standpoint, this is a discretionary NIH opportunity using the cooperative agreement mechanism, meaning awardees should expect substantial NIH program involvement compared with a standard grant. The funding instrument is the UG3/UH3 phased cooperative agreement, which generally reflects a milestone-driven approach in which an initial phase supports planning and start-up activities and a subsequent phase supports full implementation, though the FOA emphasizes that clinical trials are not allowed under this announcement. The activity category is health, and the CFDA program numbers listed include 93.233 and 93.837 through 93.840, reflecting NHLBI-related authorities and related NIH funding lines. The original closing date listed for the opportunity was March 18, 2020, and while the source text does not provide an award ceiling or expected number of awards, the stated intent is to fund multiple research centers capable of establishing and maintaining robust cohorts.

Eligibility is broad and includes many types of U.S.-based organizations and governmental entities, such as state, county, city, and 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; tribally controlled colleges and universities; tribal organizations that are not federally recognized tribal governments; public housing authorities and Indian housing authorities; nonprofits with and without 501(c)(3) status (other than institutions of higher education); for-profit organizations (other than small businesses) and small businesses; and other eligible entities. The FOA also highlights inclusion of institutions and organizations that serve groups historically underrepresented in research infrastructure, including Historically Black Colleges and Universities (HBCUs), Hispanic-serving institutions, Alaska Native and Native Hawaiian-serving institutions, and Asian American Native American Pacific Islander-serving institutions (AANAPISIs), as well as faith-based or community-based organizations and regional organizations. Foreign institutions and non-U.S. entities are not eligible to apply, and non-domestic components of U.S. organizations are not eligible; however, foreign components are allowed under NIH policy, meaning a U.S. applicant may include certain well-justified international elements of the project when permitted by the NIH Grants Policy Statement.

Overall, the program is best understood as an infrastructure-and-evidence-building initiative for rare HLBS disorders: it aims to create high-quality, longitudinal observational cohorts that can define natural history, capture meaningful outcomes (including patient-reported measures), reveal biologically grounded subtypes, and produce integrative datasets that make future diagnostic development and clinical trials more targeted, feasible, and informative.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Rare Disease Cohorts in Heart, Lung, Blood and Sleep Disorders (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): 93.233, 93.837, 93.838, 93.839, 93.840.
• This funding opportunity was created on 2019-04-04.
• Applicants must submit their applications by 2020-03-18. (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 HL 20 014

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