Single-Site Investigator-Initiated Clinical Trials (R61/R33 Clinical Trial Required) | PAR 25 028

Opportunity Information: Apply for PAR 25 028

The Single-Site Investigator-Initiated Clinical Trials (R61/R33 Clinical Trial Required) funding opportunity (PAR 25-028) is a National Institutes of Health (NIH) grant designed to help investigators both develop and carry out a single-site clinical trial that aligns with the mission of the National Heart, Lung, and Blood Institute (NHLBI). The program is meant for investigator-initiated studies, meaning the research question and trial design are proposed by the applicant rather than dictated by the government. The clinical trial must meet the NIH definition of a clinical trial (as referenced in NOT-OD-15-015) and must be relevant to NHLBI priorities, which generally cover heart, lung, blood, and sleep-related conditions and the prevention and treatment strategies connected to them.

This NOFO is broad in the kinds of single-site trials it will support. It explicitly includes efficacy trials (testing whether an intervention works under more controlled conditions), comparative effectiveness trials (comparing two or more approaches to determine which works best in real-world practice), pragmatic trials (designed to reflect routine clinical care and typical patient populations), and implementation research trials (focused on how to adopt, integrate, and sustain evidence-based interventions in real settings). The interventions under study can be therapeutic, behavioral, and/or prevention strategies, which gives applicants flexibility to propose drug, device, lifestyle, clinical practice, or community-informed approaches, as long as the study is structured as a clinical trial and fits NHLBI’s research mission.

A central feature of this opportunity is the bi-phasic, milestone-driven R61/R33 award structure. In practice, this means the project is expected to move in two stages: an initial phase focused on finalizing trial readiness (such as completing key startup activities and meeting predefined performance targets), followed by a second phase that supports the full execution of the trial once those milestones are successfully met. This structure is intended to reduce risk and ensure the trial is feasible and well-managed before committing to the later, more resource-intensive portions of the study. Applicants should plan for clear, measurable milestones and be prepared for the possibility that progression to the second phase depends on meeting them.

The application is expected to do more than argue that the study question is important. It must present a strong scientific rationale for the trial and lay out a complete scientific and operational plan that shows the trial can actually be implemented at a single site. Reviewers will be looking for credible project management plans, realistic recruitment and retention strategies, and thoughtful approaches to conducting the trial with high scientific and ethical standards. Applicants should also address how performance will be monitored against milestones, how data and safety oversight will be handled as appropriate for the study’s risk level, and how results will be communicated and disseminated so the findings can inform practice, policy, or future research.

Team structure is another emphasis. While not mandatory, the multiple PD/PI model is strongly encouraged, reflecting how clinical trials often require leadership across clinical expertise, operations, and quantitative methods. The NOFO also encourages including a PD/PI with expertise in biostatistics, clinical trial design, and trial coordination, signaling that NHLBI expects applicants to demonstrate strong methodological and operational competence, not just clinical insight. This can be satisfied through a co-leadership arrangement or a leadership team in which statistical and trial operations expertise is clearly integrated into decision-making.

Eligibility is wide and includes many organization types that commonly conduct clinical research. Eligible applicants include state, county, city, and township 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 and other tribal organizations; public housing authorities/Indian housing authorities; nonprofits (both 501(c)(3) and non-501(c)(3), excluding higher education in those categories); for-profit organizations (other than small businesses); and small businesses. The NOFO also highlights additional eligible groups such as Historically Black Colleges and Universities (HBCUs), Hispanic-serving institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISISs), faith-based or community-based organizations, eligible federal agencies, regional organizations, U.S. territories or possessions, and non-U.S. entities (foreign organizations). This breadth signals an intent to support capable trial teams across many settings, including institutions and communities that are often central to equitable recruitment and real-world implementation.

Administratively, this is a discretionary grant in the health funding category and is associated with CFDA numbers 93.233, 93.837, 93.838, 93.839, and 93.840. The sponsoring agency is NIH, and the original closing date listed is September 11, 2025. The award ceiling and expected number of awards are not specified in the provided source data, so applicants typically need to consult the full NOFO text for budget guidance, project period limits, and any institute-specific constraints.

Overall, PAR 25-028 is aimed at investigators who have a well-justified clinical question and are prepared to run a rigorously designed, single-site clinical trial with strong operational execution. The funding mechanism rewards careful planning, clear milestones, and a management structure that can recruit participants, retain them, complete the trial on time, and produce results that can be disseminated and used by the scientific and clinical communities in areas relevant to NHLBI’s mission.

• 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 2024-12-11.
• 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 25 028

[Watch] Creating a grant proposal using the step-by-step wizard inside the applicant portal: