Developmental Mechanisms of Human Structural Birth Defects (P01 Clinical Trial Not Allowed)) | RFA HD 21 013

Opportunity Information: Apply for RFA HD 21 013

The NIH funding opportunity titled "Developmental Mechanisms of Human Structural Birth Defects (P01 Clinical Trial Not Allowed)" (RFA-HD-21-013) is designed to support large, coordinated program project grants that bring multiple disciplines together to explain how major structural birth defects arise during development. The central goal is to generate a deeper, mechanistic understanding of the developmental biology and genetic causes behind significant congenital malformations by deliberately integrating basic science, translational research, and clinically oriented studies within one tightly connected program.

A key feature of this FOA is its emphasis on true synergy across projects rather than a loose collection of related studies. To control costs and keep the program focused, each P01 application is limited to exactly three component research projects plus the necessary shared cores. The three projects are expected to be interactive and mutually reinforcing, with a common central theme, focus, or objective. This theme must be anchored to one specific major developmental defect or malformation, and that defect must be meaningfully comparable between humans and an animal model in a way that is genotypic, mechanistic, biologic, phenotypic, or otherwise homologous. In practice, NIH is looking for projects where findings from model systems and human studies can directly inform one another, building a coherent story about causation and developmental pathways rather than producing parallel but disconnected results.

The scientific structure is also intentionally balanced. At least one of the three component projects must be basic research using an animal model system, and at least one must be clinical or translational in nature. The FOA allows flexibility in the choice of model organism, including both mammalian and non-mammalian models, as long as the model is genuinely useful for addressing the shared objective and the human condition being studied. Across the three projects, the work should converge on shared developmental biology, such as a common gene, pathway, process, mechanism, or phenotype relevant to the malformation of interest. This requirement pushes teams to align around a unifying hypothesis and a shared mechanistic framework, making it easier for cores, data resources, and experimental insights to be efficiently shared.

Administratively, this opportunity is offered as a discretionary NIH grant in the health-related assistance category (CFDA 93.865). It is explicitly labeled "Clinical Trial Not Allowed," which means applicants should not propose NIH-defined clinical trials under this FOA. While clinical and translational projects are required as part of the overall program, they must be structured in a way that stays outside the NIH definition of a clinical trial (for example, observational human studies, analyses of patient-derived samples, natural history efforts, genomics and functional validation pipelines, or other translational approaches that do not involve prospective assignment to an intervention and evaluation of a health-related outcome).

Eligibility is broad and includes many types of U.S.-based organizations and governmental units, such as state, county, and local 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; tribal organizations that are not federally recognized; public housing authorities/Indian housing authorities; nonprofits with and without 501(c)(3) status; for-profit organizations (other than small businesses); small businesses; and additional unspecified eligible entities. The FOA also highlights inclusion of a range of institution types often emphasized in federal funding, including Alaska Native and Native Hawaiian Serving Institutions, AANAPISIs, Hispanic-serving Institutions, Historically Black Colleges and Universities, Tribally Controlled Colleges and Universities, eligible federal agencies, faith-based or community-based organizations, regional organizations, and U.S. territories or possessions.

At the same time, there are clear limits related to foreign participation. Non-domestic (non-U.S.) entities (foreign organizations and foreign institutions) are not eligible to apply as the applicant organization, and non-domestic components of U.S. organizations are also not eligible to apply. However, foreign components are allowed under NIH policy as defined in the NIH Grants Policy Statement, meaning a U.S. applicant may include certain well-justified foreign collaborations or elements if they meet NIH rules and are scientifically necessary.

The FOA was created on December 17, 2019, and the original closing date listed is June 30, 2020. Overall, the opportunity is aimed at teams that can build a tightly integrated, three-project program focused on a specific structural birth defect, using animal-model developmental biology alongside human clinical or translational work to uncover shared mechanisms and genetic drivers in a way that produces more than the sum of its parts.

• The National Institutes of Health in the health, income security and social services sector is offering a public funding opportunity titled "Developmental Mechanisms of Human Structural Birth Defects (P01 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): 93.865.
• This funding opportunity was created on 2019-12-17.
• Applicants must submit their applications by 2020-06-30. (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 HD 21 013

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