The NHLBI Clinical Trial Pilot Studies (R34 Clinical Trial Optional) funding opportunity supports pilot studies aimed at addressing critical information gaps necessary to finalize protocols for Phase II-IV clinical trials. These pilot studies must produce results that are both scientifically necessary and sufficient to inform the design and execution of subsequent trials focused on the prevention, treatment, or management of heart, lung, blood, or sleep disorders. The R34 mechanism is not intended for protocol writing, infrastructure development, or purely mechanistic research but instead focuses on generating data to refine study populations, interventions, outcomes, statistical methods, and operational feasibility. Successful pilot studies should yield information that reduces uncertainties and minimizes protocol amendments during future full-scale clinical trials.

The program encourages diverse perspectives, requiring a plan for enhancing diverse perspectives (PEDP) as part of the application. This plan should outline strategies for fostering inclusivity, such as engaging underrepresented groups, collaborating with minority-serving institutions, and providing mentorship opportunities for early- and mid-career researchers. The PEDP will be evaluated as part of the peer review process and considered during funding decisions. Applications lacking a PEDP will be considered incomplete and withdrawn from review.

Eligible applicants include higher education institutions, nonprofit and for-profit organizations, state and local governments, tribal organizations, and other public entities. Foreign institutions are not eligible, though foreign components of U.S.-based institutions may participate. Applicant organizations may submit multiple applications, provided each is scientifically distinct. Investigators must ensure compliance with required registrations, including SAM, Grants.gov, and eRA Commons, before submission.

The funding opportunity allows budgets of up to $450,000 in direct costs over three years, with a maximum of $225,000 per year. The project period cannot exceed three years. Applications must include key attachments, such as a description of the future clinical trial, the PEDP, and documentation of FDA approval if applicable. Required registrations must be completed in advance, and applications must adhere strictly to the NIH application guidelines.

Proposals will be evaluated based on standard NIH review criteria, including significance, investigator qualifications, innovation, approach, and environment. Specific emphasis will be placed on how well the PEDP integrates diverse perspectives into the research design and implementation. Additionally, reviewers will assess the study design, feasibility, statistical methods, and plans for recruitment and retention of participants. The application must also address data management, safety monitoring, and ethical considerations.

Applications are accepted multiple times per year, aligning with standard NIH due dates. A letter of intent is recommended but not required. Funding decisions will be based on scientific merit, programmatic priorities, and the availability of funds. Successful applicants will be required to comply with NIH reporting requirements, including annual research performance progress reports and updates on PEDP implementation.