The **NHLBI Early Phase Clinical Trials for Therapeutics and/or Diagnostics for HLBS Disorders (R33 CT Required)** supports investigator-initiated Phase I clinical trials for diagnostic and therapeutic interventions aimed at heart, lung, blood, and sleep (HLBS) disorders in adults and children. This funding opportunity, issued by the **National Heart, Lung, and Blood Institute (NHLBI)**, focuses on early translational research to assess the safety and feasibility of interventions. Applicants are expected to have all regulatory approvals, drug/placebo supplies, and third-party agreements in place by the time of award, as the trial must begin within the first quarter of the project period.

The program specifically targets **Phase I clinical trials**, including bridging studies that generate clinical data allowing the extrapolation of results from one population, such as adults, to a new population, like pediatrics. The primary goal of these trials is to assess safety, while secondary objectives may include determining optimal dosing, pharmacokinetics, and pharmacodynamic responses, as well as validating biomarkers and functional measures for subsequent trials. Trials must demonstrate relevance to NHLBI's mission and address an unmet medical need or critical research gap. Mechanistic or animal studies are not eligible, and applications must align with NIH’s clinical trial definition.

Applications must include milestone-driven objectives for the **R33 mechanism**, which can support projects for up to three years with a budget not exceeding **$1,515,000 in direct costs per year**. The milestones must be measurable, time-bound, and clearly relevant to achieving study goals, including progress tracking for patient enrollment and data collection. A well-developed **Project Management Plan** is mandatory, detailing how the study will achieve its objectives on time and on budget, including contingencies for delays. Applications will be reviewed based on significance, innovation, study design, and the qualifications of the project team.

Eligible applicants include higher education institutions, nonprofits, for-profit organizations, local governments, tribal organizations, and federal agencies. Foreign institutions are not eligible, though foreign components of U.S.-based projects are allowed. Applicants must meet all NIH registration requirements, including **SAM.gov**, **Grants.gov**, and **eRA Commons**. Letters of intent are encouraged 30 days before application deadlines, which adhere to standard NIH submission cycles: **June 4, October 2, and February 3 annually**.

Applications must comply with the NIH Data Management and Sharing Policy and include detailed plans for data management, quality control, and dissemination. Specific requirements include recruitment strategies for diverse populations, adverse event monitoring, FDA regulatory status for interventions, and contingency plans for enrollment shortfalls. Applications proposing multi-site studies must demonstrate the capacity to coordinate multiple centers efficiently.

Review criteria emphasize the project’s significance, rationale, and potential to advance Phase II trials. Additional considerations include the robustness of the study design, statistical analysis, project management plans, and institutional support. NHLBI will evaluate applications based on scientific merit, program relevance, and the availability of funds. Post-award, recipients must adhere to NIH clinical trial reporting requirements, including registration and results submission to **ClinicalTrials.gov**.

Applicants are strongly encouraged to contact NHLBI program officials, such as Dr. Sumita Khatri, Dr. Daniel Frank, or Dr. Emily Tinsley, at least 12 weeks before submission to ensure alignment with NHLBI priorities. The program emphasizes diversity in research teams, innovation, and addressing critical gaps in HLBS clinical research.