Single-Site Investigator-Initiated Clinical Trials (R61/R33 Clinical Trial Required) | PAR 19 328

Opportunity Information: Apply for PAR 19 328

The Single-Site Investigator-Initiated Clinical Trials (R61/R33 Clinical Trial Required) opportunity, listed as PAR 19-328, is a National Institutes of Health grant program administered through the National Heart, Lung, and Blood Institute (NHLBI). Its main purpose is to support researchers who want to design and run their own single-site clinical trials that align with NHLBI's mission areas, meaning heart, lung, blood, and sleep-related conditions and the prevention, diagnosis, and treatment approaches connected to those fields. The FOA is specifically aimed at clinical trials that meet the NIH definition of a clinical trial and that are Phase II or later, so it is not intended for early exploratory human studies or small pilot trials that do not fit that definition.

The scope of trials supported is fairly broad as long as they are scientifically strong and clearly relevant to NHLBI priorities. The FOA allows efficacy trials (whether an intervention works under controlled conditions), comparative effectiveness trials (how one intervention performs compared to another in real-world choices), pragmatic trials (designed to reflect routine practice settings), and implementation research trials (testing strategies for adopting or integrating evidence-based interventions into real settings). Interventions can be therapeutic, behavioral, and/or preventive, which means applicants are not limited to drugs or devices; lifestyle, behavioral health, care delivery, or prevention strategies can also qualify if the study design is a true clinical trial and fits NHLBI interests.

A key feature of this program is the two-phase, milestone-driven funding structure using the R61/R33 mechanism. The R61 phase is generally used to support early, time-limited activities required to launch a trial successfully, such as finalizing protocols, establishing operational infrastructure, completing key regulatory steps, setting up data systems, or meeting recruitment-readiness benchmarks. The R33 phase supports the actual execution of the clinical trial once predefined milestones are met. Because the award is milestone-based, reviewers and program staff will expect applicants to define clear, measurable performance milestones and explain how progress will be tracked. The practical takeaway is that the application has to show not only that the science is compelling, but also that the team can execute the trial efficiently and that there are objective decision points for moving from the start-up period into full trial conduct.

Applications are expected to be comprehensive and operationally detailed. Beyond the scientific rationale and the clinical question, NHLBI anticipates a full operational plan for conducting the trial at a single site, including project management structures, participant recruitment and retention strategies, plans for trial coordination, and a description of how the study will maintain high-quality scientific conduct. That includes considerations like data collection and quality control, oversight and monitoring appropriate to risk, and plans to disseminate results. In other words, this is not just a "concept" submission; it is meant to look like a ready-to-run clinical trial package with realistic timelines and a clear management approach.

The FOA strongly encourages, but does not require, a multiple PD/PI model. This reflects how complicated trials can be and how often they require leadership that spans clinical expertise, operations, and quantitative methods. Applicants are encouraged to include a PD/PI with strong experience in biostatistics, clinical trial design, and coordination, signaling that NHLBI wants to see rigorous design choices (endpoints, power, randomization, analysis plans, handling missing data, etc.) paired with credible trial management. Even when there is a single PD/PI, the expectation is that the investigator team includes the necessary expertise to design and run a Phase II-plus clinical trial responsibly.

Because of the complexity and the NHLBI-specific fit requirements, prospective applicants are strongly encouraged to contact the appropriate NIH Scientific/Research contact before submitting. This is positioned as a practical step to help applicants confirm alignment with the FOA, clarify expectations for milestones and trial readiness, and avoid common mismatches that lead to poor review outcomes (for example, proposing a study that is not truly a clinical trial per NIH policy, proposing a multi-site design under a single-site FOA, or proposing a topic outside NHLBI's mission).

Eligibility is broad and includes many organization types across government, academia, nonprofit, and industry. Eligible applicants include state, county, city/township, and special district governments; independent school districts; public and private institutions of higher education; federally recognized tribal governments and other tribal organizations; public housing authorities; nonprofits with and without 501(c)(3) status; for-profit organizations (other than small businesses) as well as small businesses; and other entities. The FOA also explicitly highlights additional eligible categories such as Alaska Native and Native Hawaiian Serving Institutions, Hispanic-serving institutions, Historically Black Colleges and Universities, Tribally Controlled Colleges and Universities, Asian American Native American Pacific Islander Serving Institutions, faith-based or community-based organizations, U.S. territories or possessions, eligible federal agencies, and even non-U.S. (foreign) organizations and regional organizations. This broad eligibility suggests NHLBI is open to a wide range of applicant institutions as long as they can conduct a compliant, high-quality single-site Phase II or later trial and meet NIH requirements.

From the listing details, this is a discretionary grant in the health funding category, tied to CFDA numbers 93.233 and 93.837 through 93.840, which correspond to NIH/NHLBI-related assistance programs. The FOA was created on 2019-08-05, and the listing shows an original closing date of 2022-09-08. The award ceiling and expected number of awards are not specified in the provided source data, which typically means applicants need to consult the full FOA and current NHLBI guidance for budget expectations, allowable costs, and any institute-specific limits or preferences.

Overall, the program is best understood as a structured pathway for a well-developed, investigator-initiated, single-site clinical trial that is ready to move from start-up into execution using a milestone-based approach. Successful applications will read like a carefully engineered clinical trial plan: a compelling and NHLBI-relevant question, a defensible Phase II-plus design, a strong operational and recruitment strategy, clear milestones for the transition between phases, and a team with the statistical, clinical, and coordination expertise to deliver results and disseminate them in a way that advances practice and policy.

• 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 2019-08-05.
• Applicants must submit their applications by 2022-09-08. (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 19 328

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