Single-Site Investigator-Initiated Clinical Trials (R61/R33 Clinical Trial Required) | PAR 22 189

Opportunity Information: Apply for PAR 22 189

The Single-Site Investigator-Initiated Clinical Trials (R61/R33 Clinical Trial Required) funding opportunity (PAR-22-189) is a National Institutes of Health grant program designed to support researchers who want to launch and carry out their own single-site clinical trial that fits within the mission of the National Heart, Lung, and Blood Institute (NHLBI). The focus is broad in terms of trial types, as long as the work qualifies under the NIH definition of a clinical trial (as referenced in NOT-OD-15-015) and is clearly aligned with NHLBI priorities. In practical terms, this means investigators can propose trials that evaluate therapeutic approaches, behavioral interventions, or prevention strategies, and the trial can be framed as an efficacy study, a comparative effectiveness study, a pragmatic trial, and/or an implementation research clinical trial. The unifying theme is that the study is investigator-initiated, conducted at a single site, and built around a rigorous plan that can realistically be executed.

A central feature of this opportunity is its two-phase, milestone-driven award structure using the R61/R33 mechanism. This bi-phasic design is intended to reduce risk and improve accountability by tying continued funding to progress against clearly defined milestones. The first phase (R61) generally functions as a planning, start-up, and early execution period where investigators finalize operational readiness, establish trial workflows, and demonstrate that key performance targets are achievable. The second phase (R33) supports the full conduct of the trial once the project has met the predefined go/no-go criteria. Because the mechanism is milestone-driven, the application needs to be written with an operational mindset, not just a compelling scientific question. Reviewers and program staff will expect a concrete set of measurable benchmarks that show whether the trial is on track, such as timelines for regulatory approvals, site readiness, recruitment pace, retention levels, data quality indicators, and other performance metrics.

The application is expected to do two things well at the same time: make a strong scientific case for why the clinical trial should be done, and present a complete operational blueprint for how it will be carried out. On the scientific side, the proposal should clearly lay out the rationale, the target population, the intervention(s), the comparator (if applicable), endpoints and outcome measures, and the overall design logic. On the operational side, the FOA explicitly highlights the need to address project management, recruitment and retention planning, performance milestones, the scientific conduct of the trial, and dissemination of results. In other words, applicants should show they can not only design a strong trial, but also run it effectively at a single site, keep participants engaged, protect human subjects, maintain data integrity, and report and share results in a responsible and timely way.

Although not mandatory, the multiple PD/PI model is strongly encouraged. The FOA also signals that applications will be strengthened by leadership that includes clinical trial methods expertise, particularly in biostatistics, trial design, and trial coordination. This is a practical cue about what NIH and NHLBI consider common failure points in clinical trials, such as underpowered designs, weak analytic plans, unrealistic recruitment assumptions, and insufficient operational infrastructure. Having a PD/PI (or co-leader) who can credibly cover those technical and managerial dimensions can improve the likelihood that the proposed milestones are realistic and that the trial can meet them.

Eligibility is broad and includes a wide range of organization types. In addition to standard categories like public and private institutions of higher education, nonprofits (with or without 501(c)(3) status), for-profit organizations (other than small businesses), small businesses, and various levels of government (state, county, city/township, special districts), the opportunity explicitly welcomes applications from many mission-relevant and community-rooted entities. These include 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, regional organizations, US territories or possessions, eligible federal agencies, and even non-US (foreign) entities. This breadth reflects an interest in expanding where clinical trial capacity exists and supporting studies that may be embedded in diverse real-world settings, provided the project remains single-site and meets the NHLBI mission alignment requirement.

Administratively, this is a discretionary grant program under NIH, categorized within health-related funding activities, and associated with CFDA numbers 93.233, 93.837, 93.838, 93.839, and 93.840. The opportunity lists an original closing date of 2025-09-11. The award ceiling and expected number of awards are not specified in the provided source data, which usually means applicants should consult the full FOA text and any linked NHLBI or NIH guidance for budget expectations, typical award sizes, and submission cycle details.

Overall, this FOA is best understood as support for a well-justified, tightly managed, single-site clinical trial where the investigators can demonstrate both scientific importance and execution readiness. Competitive applications will read like a combined scientific argument and operations manual: a clear clinical question that matters to heart, lung, blood, and sleep health; a defensible design and analysis plan; a realistic recruitment and retention strategy; a detailed project management approach with concrete milestones; and a credible plan for conducting the trial with high quality and then disseminating the findings so they can inform practice, policy, or future research.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Single-Site Investigator-Initiated Clinical Trials (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 2022-07-12.
• Applicants must submit their applications by 2025-09-11. (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 PAR 22 189

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