Early Phase Clinical Trials for Therapeutics and/or Diagnostics for HLBS Disorders (R33 CT Required)
🏛 National Institutes of Health (HHS-NIH11)
✓ Free, no account · Source: Grants.gov · Last verified Jul 16, 2026
Can you apply?
This grant is for research organizations, academic institutions, and medical centers developing early-phase clinical trials for therapeutics and/or diagnostics targeting heart, lung, blood, and sleep (HLBS) disorders. Eligible applicants typically include NIH-eligible domestic and international institutions, though U.S. organizations are prioritized. The grant supports translational research moving promising preclinical findings toward human clinical testing. Activities funded include clinical trial design, patient recruitment and enrollment, safety monitoring, and preliminary efficacy assessments for novel HLBS treatments and diagnostic tools. The R33 mechanism requires prior R21 funding (R33 CT Required), meaning applicants must have successfully completed an R21 exploratory phase before applying for this advanced clinical trial grant.
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Program description
The objective of this funding opportunity is to support investigator-initiated, phase I clinical trials for diagnostic and therapeutic interventions for heart, lung, blood, and sleep (HLBS) disorders in adults and children. The proposed trial can be single or multisite.
Applicants applying for funding under this NOFO should be ready to initiate the clinical trial within the first quarter of the project period. Discussion, submission, and attainment of applicable regulatory (FDA, DSMB, IRB) approvals, and establishment of drug (and placebo, if applicable) supplies, and any necessary third-party agreements should be established by the time of award. If time and support for these and other pre-clinical and/or trial readiness activities are desired, applicants should consider the companion NOFO which utilizes an R61/R33 phased approach.
Who can apply
Eligible applicants
How to apply
Application links
Required documents
- SF-424 (R&R) Federal Application for Research
- R&R Subaward Budget Attachment (if applicable)
- Project Narrative (research strategy, significance, innovation, approach, including clinical trial protocol)
- Biographical Sketches for all key personnel (NIH format)
- References and Supporting Documents
- IRB Approval or Approval Pending documentation
- Letters of Support from clinical sites and institutional partners
- Data Safety Monitoring Plan
- Human Subjects Protection documentation
- Vertebrate Animal Use documentation (if applicable)
- Budget Justification
- Facilities and Resources documentation
Program contact
- 👤 National Institutes of Health
- 📧 grantsinfo@nih.gov
- 📞 301-402-2541
Funding track record
Recent awards under CFDA 93.838 from the last 3 years — real organizations that won funding through this same program.
Top 10 Largest Recent Awards
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$64,183,283
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$53,344,199
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$43,989,024
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$38,428,037
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$34,243,478
-
$27,859,190
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$26,861,834
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$26,624,924
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$26,063,829
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$25,153,102
Top States by Funding
- MA 14 awards $246.9M
- CA 15 awards $199.1M
- CO 8 awards $139.0M
- IL 7 awards $107.8M
- NC 4 awards $95.8M
Source: USAspending.gov — federal spending transparency. Data covers last 3 years.
Funding history
Annual funding for this program — Federal obligations (CFDA 93.838). How funding has trended year over year.
| 2024 | $760,925,134 | |
| 2025 | $789,408,855 |
FAQ
What is the R33 mechanism and why does it require prior R21 funding?
The R33 is a phased research grant designed to support advanced clinical trial work after successful completion of an exploratory R21 phase. The R21 establishes feasibility; the R33 then funds the expanded clinical testing. This grant explicitly requires R33 CT funding, meaning you must have an active or recently completed R21 award in the same research area.
What HLBS disorders qualify for this funding?
Eligible disorders include cardiovascular diseases, lung diseases, blood disorders, and sleep disorders under NHLBI's mission. Your research should target therapeutics or diagnostic tools for these conditions. Contact the specific NHLBI Division program officer to confirm your disease focus is within scope.
What activities can the grant fund?
This mechanism supports early-phase clinical trials, including trial design and protocol development, patient recruitment and informed consent, safety and efficacy monitoring, biomarker assessments, and preliminary outcome data collection. Preclinical laboratory work is not a primary focus; the emphasis is on human subject research.
How competitive is this grant and what is the typical funding range?
R33 CT grants are moderately competitive, with success rates typically in the 15-25% range for NIH clinical research. Award amounts typically range from $250,000 to $750,000 per year, depending on the scope and complexity of the proposed clinical trial. Budget should be justified by the trial's size and requirements.
What is the application deadline and when can I submit?
The application deadline is January 7, 2027. The application portal opens December 5, 2024, so you should begin preparation immediately to allow time for institutional approvals, IRB review, and application submission before the deadline.
💡 Tips for applicants
- Secure your R21 foundation first: Since this is R33 CT Required, ensure you have completed or have active R21 funding in the same research area. Your R33 application must explicitly reference the prior R21 award and explain how you've addressed initial feasibility findings.
- Develop a rigorous clinical trial protocol: Reviewers will scrutinize your trial design, patient population, inclusion/exclusion criteria, and sample size justification. Work closely with a biostatistician and clinical trial design expert to ensure your protocol is sound and feasible.
- Demonstrate patient recruitment and retention capacity: Show concrete evidence that you can enroll the proposed number of subjects. Include letters of support from clinical partners, patient registries, or patient advocacy organizations. Underestimated recruitment is a common reason for slow progress.
- Address safety and ethics upfront: Clearly outline safety monitoring plans, data safety monitoring board composition, adverse event reporting procedures, and IRB/ethics review status. Early-phase trials require robust safety infrastructure to gain reviewer confidence.
- Budget realistically for clinical trial infrastructure: Account for regulatory compliance, IRB submissions, informed consent processes, patient visit costs, data management systems, and safety monitoring. Undersized budgets that don't reflect actual trial costs will lower your competitiveness.
⚠️ Common mistakes
Many R33 CT applications fail because applicants lack a completed R21 phase or fail to clearly document how their R33 work advances beyond initial R21 findings. Additionally, overly ambitious trial designs with unrealistic recruitment timelines or insufficient safety monitoring plans are frequently rejected. Reviewers also penalize applications that don't adequately demonstrate institutional or clinical partner commitment to the trial's success.
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