An Intergenerational Precision Medicine Research Program for the Study of Factor VIII Immunogenicity in Severe Hemophilia A: Hemophilia A Analytical Cohort Research Program (UG3/UH3 Clinical Trial Not Allowed) | RFA HL 22 004

Opportunity Information: Apply for RFA HL 22 004

This NIH funding opportunity (RFA-HL-22-004) supports the creation of a Hemophilia A Analytical Cohort Research Program, or HARP, focused on severe hemophilia A and the immunogenicity of factor VIII (FVIII). The central scientific problem behind the program is that some patients develop inhibitory antibodies (inhibitors) against infused FVIII, which can make standard replacement therapy less effective or ineffective. The FOA is set up to build an intergenerational precision-medicine resource that can help researchers understand why inhibitors develop by linking detailed clinical information across pregnancy, birth, and early childhood with high-quality, well-annotated biospecimens. The long-term goal is to enable future studies that can predict, prevent, or better manage FVIII inhibitor development.

The program is designed around building and supporting a cohort that begins as early as the antenatal period and continues through neonatal and pediatric follow-up. HARP is expected to work hand-in-hand with an already established consortium of clinical centers that will be responsible for identifying participants, recruiting and enrolling families, and conducting follow-up visits and assessments. In practice, that means HARP acts as the coordinating and technical backbone for a network that is actually seeing patients, while ensuring that data and specimens are collected consistently across sites, handled correctly, and curated so they can be used for rigorous research later.

A major deliverable under this FOA is the creation of a unique, shareable biospecimen repository tied to robust intergenerational clinical and demographic data. The emphasis on "intergenerational" is important: the program is not only interested in the child with severe hemophilia A, but also in capturing relevant information and samples that help interpret inherited and early-life factors that might shape immune responses to FVIII. To make that possible, HARP must provide strong data management systems, laboratory support, and biospecimen operations so that samples are processed, stored, tracked, and annotated in a way that preserves their scientific value and allows other investigators to use the resource in the future.

Beyond building infrastructure, HARP is also expected to develop and carry out hypothesis-driven research protocols that use the cohort data and biospecimens. In other words, this is not just a registry or biobank-building project. The awardee is expected to write and implement practical, scientifically grounded procedures for collecting longitudinal data and specimens, and to use some of those materials during the project period to answer well-defined research questions related to FVIII immunogenicity. The FOA highlights the need for biostatistics and data analytics support, along with laboratory expertise that can include multi-omics approaches, reflecting an expectation that modern, high-dimensional data types may be generated and analyzed as part of the program.

Structurally, the funding mechanism is a cooperative agreement using the UG3/UH3 phased award structure, and it is explicitly designated "Clinical Trial Not Allowed." The cooperative agreement format means NIH will have substantial programmatic involvement, and the phased structure generally implies an initial planning/start-up phase (UG3) with milestones that must be met before transitioning to an implementation phase (UH3). In this case, those milestones would typically align with standing up the coordination infrastructure, finalizing protocols, ensuring data and specimen pipelines are operational, and demonstrating readiness to support enrollment and longitudinal follow-up at scale, although the exact milestone expectations would be specified in the full FOA text and negotiations with NIH staff.

The scope of responsibilities for the HARP awardee is broad and operationally demanding. It includes overall project coordination and administration; development, standardization, and rollout of research protocols and operating procedures; centralized data coordination and management; biostatistics and analytic planning; laboratory operations that may include multi-omics assays; and biorepository management to ensure specimens remain usable and well-documented over time. Just as importantly, HARP is expected to collaborate closely with the participating clinical centers so that the cohort can be recruited and followed in a consistent, pragmatic way, and so that the resulting dataset and specimen collection are coherent across all sites rather than fragmented by local practices.

Eligibility for this opportunity is wide and includes many types of U.S.-based organizations, such as state and local governments, public and private institutions of higher education, nonprofit organizations (with or without 501(c)(3) status), for-profit organizations (other than small businesses), and small businesses. The FOA also explicitly calls out a range of institutions and groups as other eligible applicants, including Historically Black Colleges and Universities, Hispanic-serving institutions, Tribally Controlled Colleges and Universities, Alaska Native and Native Hawaiian Serving Institutions, and community- or faith-based organizations, among others. At the same time, non-domestic (non-U.S.) entities and foreign institutions are not eligible to apply, and non-domestic components of U.S. organizations are not eligible. However, foreign components are allowed as defined by NIH policy, meaning a U.S. applicant may incorporate certain international elements in the project if they meet NIH requirements and are appropriately justified.

Administratively, the opportunity is offered by the National Institutes of Health as a discretionary cooperative agreement in the health category (CFDA 93.839). The original closing date listed for the competition was October 19, 2021, and the opportunity record was created on September 9, 2021. Overall, the FOA is essentially a call to build a national-level coordination and analytics hub that can reliably support an early-life severe hemophilia A cohort, generate a deeply annotated intergenerational dataset and biospecimen resource, and carry out targeted, hypothesis-driven studies that move the field closer to understanding and ultimately reducing FVIII inhibitor risk.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "An Intergenerational Precision Medicine Research Program for the Study of Factor VIII Immunogenicity in Severe Hemophilia A: Hemophilia A Analytical Cohort Research Program (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): 93.839.
• This funding opportunity was created on 2021-09-09.
• Applicants must submit their applications by 2021-10-19. (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 HL 22 004

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