NIH Exploratory/Developmental Research Project Grant (Parent R21 Basic Experimental Studies with Humans Required) | PA 25 307

Opportunity Information: Apply for PA 25 307

The NIH Exploratory/Developmental Research Project Grant (Parent R21 Basic Experimental Studies with Humans Required), funding opportunity number PA 25-307, is an NIH grant mechanism designed to help researchers launch early-stage, high-potential projects that are still in the exploratory or developmental phase. The R21 is meant for ideas that may be bold or somewhat risky, where the payoff could be a major advance in understanding or capability. NIH positions this mechanism as a way to support work that could open new directions in biomedical, behavioral, or clinical research, including the creation or testing of novel techniques, agents, methodologies, models, or research applications. In practice, the R21 is often used to generate initial proof-of-concept data, refine an approach, or demonstrate feasibility so the work can later scale into a larger, more definitive project.

A defining feature of this specific Parent Notice of Funding Opportunity is that it is intended for basic science experimental studies involving humans that are still considered clinical trials under NIH rules. NIH describes these as prospective basic science studies involving human participants (as referenced in NOT-OD-18-212). To fit this category, the study must prospectively assign human participants to one or more conditions, meaning the investigators deliberately manipulate one or more independent variables (for example, assigning participants to different tasks, stimuli, exposures, or experimental conditions), and then measure biomedical or behavioral outcomes in humans. The key point is the purpose: the work is meant to understand fundamental aspects of biological or behavioral phenomena, not to test a specific intervention for a practical product-development or clinical-implementation goal. If the study is aimed at a specific application such as evaluating a treatment strategy, optimizing a care pathway, validating a diagnostic for immediate use, or building toward a commercializable product, NIH indicates that applicants should use a different funding opportunity announcement that is labeled Clinical Trials Required or Clinical Trial Optional, as appropriate.

Because this is a Parent R21, it is broadly available across NIH, but proposed projects must align with the programmatic interests and scientific mission of at least one participating NIH Institute or Center. That means applicants typically need to identify which NIH Institute or Center best matches the topic area (for example, based on disease area, population, organ system, behavioral domain, or foundational science focus) and ensure the application clearly fits that Institute or Center's priorities. This alignment is important because it influences where the application can be assigned for funding consideration.

Eligibility is intentionally broad and includes many organization types across the public, private, nonprofit, and academic sectors. Eligible applicants include state, county, city or township governments, and special district governments, as well as independent school districts. Higher education institutions are eligible, including public/state-controlled and private institutions. Tribal entities are included, such as federally recognized Native American tribal governments and other Native American tribal organizations, along with additional categories highlighted by NIH such as Tribally Controlled Colleges and Universities (TCCUs). Nonprofits may apply whether or not they have 501(c)(3) status, and for-profit organizations other than small businesses are eligible, in addition to small businesses. Public housing authorities and Indian housing authorities are also listed among eligible applicants. NIH also explicitly notes additional eligible applicant categories that include 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), faith-based or community-based organizations, eligible federal agencies, U.S. territories or possessions, regional organizations, and even non-U.S. entities (foreign organizations), reflecting NIH's broad openness to strong science wherever it can be appropriately conducted under NIH policy.

Administratively, this opportunity is run by the National Institutes of Health and is categorized as a discretionary grant program. It falls under health-related federal assistance program areas and is associated with multiple CFDA numbers (now commonly referenced as assistance listing numbers), including 93.173, 93.213, 93.233, 93.242, 93.273, 93.279, 93.361, 93.837, 93.838, 93.839, 93.840, 93.865, 93.866, and 93.867, reflecting how parent NIH funding opportunities can span many Institutes and Centers and program areas. The posted opportunity shows an original closing date of 2028-01-07, indicating a multi-year window during which standard NIH submission cycles and due dates typically apply under the parent announcement structure.

Overall, this FOA is best understood as NIH's main entry point for early-stage, hypothesis-generating or mechanism-probing experimental work in humans that still meets the formal NIH definition of a clinical trial, but remains fundamentally basic research in intent. It is aimed at research that manipulates conditions in human participants to learn how underlying biological or behavioral processes work, producing insights or methods that can later support more applied clinical research, translational development, or larger-scale studies under other NIH mechanisms.

• The National Institutes of Health in the education, health, income security and social services sector is offering a public funding opportunity titled "NIH Exploratory/Developmental Research Project Grant (Parent R21 Basic Experimental Studies with Humans Required)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.173, 93.213, 93.233, 93.242, 93.273, 93.279, 93.361, 93.837, 93.838, 93.839, 93.840, 93.865, 93.866, 93.867.
• This funding opportunity was created on 2024-12-18.
• Applicants must submit their applications by 2028-01-07.
• 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.

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