NHLBI Early Phase Clinical Trials for Therapeutics and/or Diagnostics (R61/R33 Clinical Trial Required) | PAR 18 683

Opportunity Information: Apply for PAR 18 683

The NHLBI Early Phase Clinical Trials for Therapeutics and/or Diagnostics (R61/R33 Clinical Trial Required), PAR 18-683, is a National Institutes of Health grant opportunity designed to fund investigator-initiated Phase I clinical trials that test new diagnostic or therapeutic interventions related to heart, lung, blood, and sleep (HLBS) disorders. The program supports studies in both adults and children, and it allows either single-site or multi-site trial structures depending on what best fits the science and the operational realities of the proposed work. A central requirement is that the proposed study must meet the NIH definition of a clinical trial and must clearly align with the NHLBI mission and priorities, with applicants encouraged to consult NHLBI resources to make that alignment explicit.

A defining feature of this opportunity is its two-stage, milestone-driven award structure using the R61/R33 mechanism. The first phase (R61) functions as an early, preparatory period to complete essential pre-trial activities that are often critical for a successful Phase I launch. Examples highlighted in the announcement include stability testing, shipping and handling studies, and site training, but in practice this phase is meant to finalize the operational readiness needed to begin enrolling participants safely and efficiently. Progression to the second phase (R33), which supports execution of the clinical trial itself, is dependent on meeting clearly defined performance milestones. This milestone-based approach reflects the program’s emphasis on feasibility, readiness, and accountable trial conduct, and it signals that applicants should treat operational planning as a core scientific component rather than an administrative afterthought.

Applications are expected to present a strong scientific rationale for why the proposed intervention should be tested in humans at the Phase I level, along with a comprehensive scientific and operational plan for running the trial. That plan should address how the project will be managed day-to-day, how participants will be recruited and retained, what milestones will be used to track progress and readiness (and how success will be judged), and how the investigators will ensure high-quality trial conduct. The FOA also emphasizes dissemination of results, indicating that investigators should describe how findings will be communicated to the scientific community and other stakeholders, consistent with expectations for transparency and impact in clinical research.

Team structure and expertise are treated as particularly important because early-phase trials are complex and resource-intensive. While not required, the multiple PD/PI model is strongly encouraged, reflecting the reality that Phase I trials often benefit from shared leadership across clinical, methodological, and product-focused domains. Applicants are encouraged to assemble teams that include biostatistics expertise, clinical trial design and coordination capability, and, when relevant, product manufacturing and formulation experience. This expectation signals that NHLBI is looking for proposals that combine clinical insight with rigorous trial methodology and practical readiness to handle the investigational product or diagnostic under real-world clinical conditions.

The FOA strongly encourages potential applicants to contact the appropriate NHLBI Scientific/Research contact before submitting an application. This is presented as a practical step given the complexity of clinical trial applications and the need to ensure the proposed work fits the FOA’s objectives. NHLBI staff can help applicants interpret program goals, confirm fit with NHLBI priorities, and potentially identify common issues that weaken clinical trial applications, such as underdeveloped milestone plans, incomplete operational readiness, or insufficient expertise on the team.

Eligibility is broad and includes many types of U.S.-based organizations: state, county, and local governments; special district governments; independent school districts; public and private institutions of higher education; federally recognized Native American tribal governments; tribal organizations that are not federally recognized; public housing authorities; nonprofits with and without 501(c)(3) status; for-profit organizations (other than small businesses); and small businesses. The announcement also explicitly notes eligibility for a range of institution types often highlighted in NIH programs, including Hispanic-serving institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, and Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), as well as faith-based or community-based organizations and U.S. territories or possessions. Foreign institutions (non-U.S. entities) are not eligible to apply directly, but non-domestic components of U.S. organizations may participate, and foreign components as defined by NIH policy are allowed, which can be important for collaborations, specialized assays, or recruitment strategies that require international participation under a U.S.-led application.

In short, this NHLBI opportunity funds early human testing of promising HLBS-related therapeutics and diagnostics, with a built-in, two-phase structure that first supports final trial preparation and then supports the Phase I clinical trial once predefined milestones are met. Competitive applications will read like executable clinical trial blueprints: a clear justification for moving into Phase I, a detailed operational and statistical plan, a realistic recruitment and retention strategy, and a team that clearly demonstrates it can manage both the scientific and logistical demands of early-phase clinical research.

• 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.
• This funding opportunity was created on 2018-02-27.
• Applicants must submit their applications by 2021-01-07. (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.

Apply for PAR 18 683

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