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

Frequently Asked Questions (FAQs)

What is the NHLBI Early Phase Clinical Trials for Therapeutics and/or Diagnostics (R61/R33 Clinical Trial Required) opportunity?

This is a National Institutes of Health (NIH) funding opportunity from the National Heart, Lung, and Blood Institute (NHLBI) intended to support investigator-initiated Phase I clinical trials for new diagnostic or therapeutic interventions related to heart, lung, blood, and sleep (HLBS) disorders. It uses the R61/R33 phased award mechanism and requires that the application propose a clinical trial as defined by NIH.

What kinds of studies does this FOA support?

The program supports Phase I clinical trials that test novel therapeutics and/or diagnostics relevant to HLBS disorders. The proposed study must meet the NIH definition of a clinical trial and must clearly align with the NHLBI mission and priorities.

Are both adult and pediatric studies allowed?

Yes. The FOA supports studies in both adults and children.

Can the trial be single-site or multi-site?

Yes. The FOA allows either a single-site or multi-site structure, depending on what best fits the scientific objectives and the operational realities of the proposed work.

What is the R61/R33 mechanism and how does it work in this program?

This opportunity uses a two-stage, milestone-driven structure. The first stage (R61) supports early, preparatory activities needed to get the Phase I trial ready to launch. The second stage (R33) supports execution of the Phase I clinical trial itself. Transition from R61 to R33 depends on meeting predefined performance milestones.

What is the purpose of the R61 phase?

The R61 phase functions as an early, preparatory period focused on completing essential pre-trial activities required for operational readiness. Examples mentioned include stability testing, shipping and handling studies, and site training. More broadly, this phase is meant to finalize readiness so enrollment can begin safely and efficiently.

What is the purpose of the R33 phase?

The R33 phase supports the conduct of the Phase I clinical trial itself, after the project demonstrates readiness by meeting the milestones established for the R61 phase.

How does a project move from the R61 phase to the R33 phase?

Progression is milestone-based. The application is expected to define clear performance milestones and how success will be judged. Meeting those milestones is required to transition into the R33 phase.

What does “milestone-driven” mean in practical terms for applicants?

It means the application should treat operational planning and readiness as core elements of the project. Applicants should specify measurable milestones that reflect feasibility and trial readiness (and later trial progress), explain how milestones will be tracked, and define objective criteria for determining whether milestones have been met.

What scientific justification is expected for a Phase I human study?

Applications are expected to present a strong scientific rationale explaining why the intervention is ready to be tested in humans at the Phase I level.

What planning elements should be included to show the trial is executable?

The FOA emphasizes a comprehensive scientific and operational plan, including day-to-day project management, recruitment and retention approaches, milestone definitions and success criteria, and plans to ensure high-quality trial conduct.

What does the FOA say about recruitment and retention?

Applicants are expected to describe how participants will be recruited and retained as part of the operational plan for running the trial.

Does the FOA expect a statistical or biostatistics component on the team?

Yes. Applicants are encouraged to include biostatistics expertise, reflecting the expectation for rigorous clinical trial design and conduct.

Is the multiple PD/PI model required?

No. The multiple PD/PI model is not required, but it is strongly encouraged because early-phase trials often benefit from shared leadership across clinical, methodological, and product-focused domains.

What types of expertise does NHLBI expect on the project team?

The FOA signals that teams should be structured to handle early-phase trial complexity. It encourages inclusion of expertise in biostatistics, clinical trial design and coordination, and (when relevant) product manufacturing and formulation.

What does the FOA emphasize about trial quality and oversight?

The application should address how investigators will ensure high-quality trial conduct, including clear operational planning and management approaches suitable for early-phase clinical research.

Are applicants expected to share or disseminate results?

Yes. The FOA emphasizes dissemination of results. 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.

Is contacting NHLBI staff before submitting required?

It is strongly encouraged. The FOA highlights pre-application contact with the appropriate NHLBI Scientific/Research contact as a practical step to help ensure fit with program objectives and NHLBI priorities.

Why does the FOA encourage contacting an NHLBI Scientific/Research contact before applying?

Because clinical trial applications are complex and must align with NHLBI priorities and FOA expectations. NHLBI staff can help applicants interpret program goals, confirm fit, and identify common weaknesses such as underdeveloped milestone plans, incomplete operational readiness, or insufficient team expertise.

Who is eligible to apply?

Eligibility is broad and includes many U.S.-based organization types, including 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.

Are minority-serving institutions and community-based organizations eligible?

Yes. The FOA explicitly notes eligibility for a range of institution types commonly referenced in NIH programs, including Hispanic-serving institutions, HBCUs, TCCUs, Alaska Native and Native Hawaiian Serving Institutions, and AANAPISIs, as well as faith-based or community-based organizations and U.S. territories or possessions.

Can foreign institutions apply directly?

No. Foreign (non-U.S.) institutions are not eligible to apply directly under this opportunity.

Can a U.S. applicant include international collaborators or activities?

Yes. The FOA notes that non-domestic components of U.S. organizations may participate and that foreign components (as defined by NIH policy) are allowed. This can support collaborations, specialized assays, or recruitment strategies requiring international participation under a U.S.-led application.

What is the core focus area for interventions supported by this FOA?

The intervention must be related to heart, lung, blood, and sleep (HLBS) disorders and must align clearly with NHLBI mission and priorities. Applicants are encouraged to consult NHLBI resources and make that alignment explicit in the application.

What is the overall “best fit” profile for a competitive application described by the FOA?

Competitive applications are positioned as executable clinical trial blueprints: a clear justification for Phase I testing, a detailed operational and statistical plan, a realistic recruitment and retention strategy, well-defined milestones tied to readiness and progress, and a team with the expertise to manage both the scientific and logistical demands of early-phase clinical research.