The National Institutes of Health (NIH) is planning a suite of five cross-institute trial Notices of Funding Opportunity (NOFOs) that it says would give investigators one set of instructions per trial type.
Dr. Marta Čeko of the NCCIH Division of Intramural Research prepares a participant for a CAT scan in an NCCIH study on pain. Credit: National Center for Complementary and Integrative Health, National Institutes of Health
On Nov. 10, NIH said its institutes are jointly building broad clinical trial NOFOs organized by trial type. Historically, many institutes wrote their own trial NOFOs with their own instructions and review criteria.
The new model is one shared NOFO per trial type: feasibility, early to definitive, multisite, pragmatic and implementation, and network trials. For example, a feasibility trial would go through the same NOFO whether it is for a heart, neurology or other study. NIH says institutes will signal their priorities through institute, center and office (ICO) profile pages, strategic plans and Highlighted Topics instead of NOFOs, which is how institutes have traditionally indicated which diseases and research areas they wanted.
The change follows NIH’s consolidation of career development (K) awards, the reclassification of basic experimental studies with humans and a cut in active NOFOs from more than 800 at the start of 2025 to fewer than 500 by year’s end.
NIH intends the new NOFOs to apply across institutes and sit alongside the parent announcements for clinical trial research project grants (R01) and exploratory/developmental grants (R21), meaning investigators can still submit trials through those existing broad announcements instead of one of the new trial-type NOFOs. NIH said it will roll the new NOFOs out in phases.
A National Heart, Lung, and Blood Institute (NHLBI) official presented the trial suite in May at the Society for Clinical Trials meeting. The slides said NIH might publish the new NOFOs in late 2026 or early 2027. As of Nov. 12, none have been posted.
NIH said the changes will make it easier for investigators to find the right NOFO, provide consistent instructions for similar trial types, strengthen methodological rigor, make co-funding across institutes easier and improve internal tracking of trials.
NIH said institutes will still be able to issue their own targeted trial NOFOs when there is a programmatic need, though it did not say how it would decide when that need exists.
Critics warn of lost funding signals
While NIH says the trial suite, along with other recent changes, will simplify processes that differ across institutes, some critics of NIH’s broader NOFO cuts have raised concerns about under-studied areas, early-career investigators and smaller institutions.
Elizabeth Ginexi, a former NIH program officer, argued that fewer NOFOs could mean less protection for under-studied areas.
“When you eliminate targeted NOFOs, you eliminate the funding signal for exactly those areas of science that would otherwise be overlooked,” she wrote in a Substack post.
Granted AI said, “Early-career researchers without established program-officer relationships, or investigators new to NIH from non-NIH-funded fields, will have a harder time finding the right submission home for their work.” Granted AI also wrote that the shift is not “necessarily bad” for an application’s chances.
No outside groups have publicly backed the changes, but two NIH institutes already use a similar model. The National Center for Complementary and Integrative Health (NCCIH) moved most of its trials to a trial-type system in 2017, and NHLBI funded 218 investigator-initiated trials through a similar set of NOFOs from fiscal 2017 to 2024.
Filed Under: clinical trials, Drug Discovery, Regulatory affairs
