NHLBI Early Phase Clinical Trials for Therapeutics and/or Diagnostics (R61/R33 Clinical Trial Required) | PAR 21 119

Opportunity Information: Apply for PAR 21 119

The NHLBI Early Phase Clinical Trials for Therapeutics and/or Diagnostics (R61/R33 Clinical Trial Required) funding opportunity (PAR-21-119) is an NIH grant program designed to move promising heart, lung, blood, and sleep (HLBS) innovations into first-in-human testing. Its central goal is to support investigator-initiated Phase I clinical trials for both therapeutic and diagnostic interventions, with relevance to adults and/or children. The program is built for projects that are ready to transition from late preclinical development into a tightly planned early clinical study, and it recognizes that many otherwise strong Phase I concepts stall because final preparatory work (like manufacturing readiness, stability confirmation, or site readiness) is not fully supported elsewhere.

A key feature of this FOA is its two-stage, milestone-driven structure using the R61/R33 mechanism. The R61 phase functions as a time-limited “launch” period intended to complete essential final pre-trial tasks that directly enable the proposed Phase I clinical trial. The FOA is explicit that R61 activities must be tied to the specific therapeutic or diagnostic being advanced and must be necessary preparation for clinical trial execution. Examples highlighted in the opportunity include stability testing, shipping and handling studies (often critical for biologics, cell-based products, devices, or temperature-sensitive diagnostics), and site training activities that ensure protocol consistency and participant safety. In other words, the R61 phase is not meant for broad exploratory research; it is meant to remove the last practical barriers to starting the clinical trial.

The second stage, the R33 phase, supports the actual start-up and implementation of the Phase I clinical trial. This can include the operational components required to run an early-stage study, such as initiating sites, enrolling participants, collecting and managing clinical data, carrying out safety monitoring, and completing the planned trial activities. The trial itself may be structured as a single-site or a multi-site study, giving applicants flexibility based on recruitment needs, specialized clinical capabilities, or the complexity of the intervention/diagnostic and required assessments. Because the overall award is milestone-based, progression from the R61 phase into the R33 phase is expected to depend on meeting predefined readiness criteria, which encourages realistic planning and clear go/no-go decision points.

In terms of who can apply, eligibility is broad and includes many types of U.S.-based organizations. Eligible applicants listed in the source include 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 other than federally recognized tribal governments; public housing authorities/Indian housing authorities; nonprofit organizations (with or without 501(c)(3) status, excluding institutions of higher education); for-profit organizations (other than small businesses); small businesses; and other organizations. The FOA also calls out additional eligible applicant types such as Historically Black Colleges and Universities (HBCUs), Hispanic-serving Institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, and Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), along with faith-based or community-based organizations, eligible federal agencies, regional organizations, and U.S. territories or possessions.

Foreign eligibility is more limited and nuanced. Non-domestic (non-U.S.) entities and foreign institutions are not eligible to apply as applicant organizations. However, non-domestic components of U.S. organizations are eligible, and “foreign components” are allowed as defined by the NIH Grants Policy Statement, meaning that certain parts of the work can be performed outside the U.S. when justified and appropriately structured under NIH rules, even though the primary applicant organization must be domestic.

Administrative details from the listing indicate this is a discretionary grant program under NIH, categorized under health, with CFDA numbers including 93.233 and 93.837 through 93.840. The opportunity was created on 2021-01-15, and the listing notes an original closing date of 2024-01-07. The award ceiling and expected number of awards are not specified in the provided source excerpt, which usually means applicants need to consult the full FOA text and any related NHLBI funding policy pages for budget guidance, project period constraints, and the most current submission dates or reissue status.

Overall, this FOA is best suited for teams that already have a well-defined therapeutic or diagnostic candidate and a Phase I clinical trial concept that is close to execution, but still needs targeted, last-step preclinical and operational work to ensure the study can begin safely and smoothly. The structure is meant to reduce the common gap between “almost ready” development and an actual first-in-human trial by funding both final preparation (R61) and trial implementation (R33) in one connected, milestone-governed pathway.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "NHLBI Early Phase Clinical Trials for Therapeutics and/or Diagnostics (R61/R33 Clinical Trial Required)" 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 2021-01-15.
• Applicants must submit their applications by 2024-01-07. (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.

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