Effect of the 2025 National Institutes of Health grants disruption on first-time and mechanism-first principal investigators: a cohort study of 80,976 active awards
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Objective
To estimate the adjusted relative risk (RR) of administrative grant disruption faced by first-time and mechanism-first principal investigators (PIs) during the 2025 National Institutes of Health (NIH) grant disruptions.
Design
Retrospective cohort study linking NIH RePORTER data to a publicly curated registry of grants disrupted in 2025.
Setting
All NIH active research grants in fiscal years 2024 to 2025.
Participants
80,976 active projects: 4,961 disrupted during the wave that peaked in May 2025, 76,015 non-disrupted controls.
Main outcome measures
Adjusted RR of disruption by two pre-specified first-time PI constructs: absolute first-time PI (no prior NIH grant) and mechanism-first PI (no prior NIH grant with the same activity code). Modified Poisson regression with institution-clustered standard errors adjusted for project, institutional, and geographic covariates. A pre-specified fiscal year 2024 common-anchor analysis addressed year-of-disruption confounding.
Results
Of 4,961 disrupted grants, 237 (4.8%) had an absolute first-time PI and 396 (8.0%) had a mechanism-first PI. After adjustment, absolute first-time PIs faced 77% elevated risk of disruption (RR 1.77, 95% CI 1.34 to 2.32) and mechanism-first PIs faced 57% elevated risk (RR 1.57, 1.16 to 2.11). Under the common-anchor analysis, the absolute first-time effect attenuated to RR 1.22 (0.95 to 1.58); the mechanism-first effect persisted (RR 1.48, 1.07 to 2.06). The elevated risk was concentrated in research-mechanism grants (RR 1.78, 1.26 to 2.52) and was robust across 8 of 9 pre-specified sensitivity analyses. The Track A start-time construct, which asks whether the disrupted project was the PI’s debut grant, yielded null estimates (RR 0.98, 0.93 to 1.04), with any effect concentrated entirely in newly started projects.
Conclusions
First-time and mechanism-first PIs faced disproportionately elevated risk of disruption during the 2025 NIH wave, concentrated in research-mechanism grants and robust to year-confounding-free identification. The relevant exposure was being early-career at the moment of administrative action, not at project initiation. The findings have direct implications for workforce equity in US biomedical research.
Key messages
What is already known on this topic
The 2025 National Institutes of Health grant disruption wave affected approximately 5,500 active awards across termination, freezing, and reinstatement statuses, with documented disproportionate impact on certain research areas, organisational types, and geographic regions.
Whether the wave disproportionately affected investigators at specific career stages, particularly first-time principal investigators (PI), has not been formally analyzed using adjusted estimates from the full NIH grant universe.
Methodological choices in defining first-time PI status, including the distinction between start-time and index-time exposures and the confounding role of project lifecycle stage, have not been systematically addressed in workforce analyses of the 2025 disruption.
What this study adds
After adjustment for mechanism, NIH institute, log cost, project age, support year, application type, institution type, and US region, absolute first-time PIs faced a 77% elevated relative risk of disruption (RR 1.77, 95% CI 1.34 to 2.32), and mechanism-first PIs faced a 57% elevated risk (RR 1.57, 1.16 to 2.11).
The signal persists in a pre-specified fiscal year 2024 common-anchor analysis designed to eliminate year-of-disruption confounding, with a mechanism-first relative risk of 1.48 (1.07 to 2.06).
The elevated risk is concentrated in research-mechanism grants and is robust across eight of nine pre-specified sensitivity analyses, indicating that administrative disruption fell disproportionately on the most vulnerable career stage in the biomedical research workforce.
The risk reflects PI status at the calendar moment of disruption (index-time), not at project initiation (start-time), a distinction with direct implications for how workforce vulnerability is operationalised in future analyses of funding shocks.
