First in Human and Early Stage Clinical Trials of Novel Investigational Drugs or Neuromodulatory Device-based Interventions for Psychiatric Disorders (U01 Clinical Trial Required) | PAR 25 180

FAQs: NIH PAR-25-180 (U01) Early Stage Clinical Trials for Psychiatric Disorders

1) What is PAR-25-180 trying to fund?

PAR-25-180 is an NIH Notice of Funding Opportunity that supports milestone-driven, early stage clinical trials focused on psychiatric disorders where there are major unmet treatment needs. The intent is practical and development-focused: generate strong early human evidence that reduces uncertainty ("de-risks" the program) and helps promising interventions move toward follow-on funding and, ultimately, FDA-approved treatment options.

2) What types of interventions are supported?

The opportunity supports (1) new investigational drugs and (2) novel neuromodulatory device-based interventions. It also allows device approaches and combination treatment strategies when appropriate, reflecting that some psychiatric conditions may benefit from multimodal interventions.

3) What stage of clinical research is the NOFO focused on?

The NOFO emphasizes first-in-human (FIH) and other early clinical studies. It also addresses Phase II-enabling work and Phase II/proof-of-concept (PoC) contexts, with an emphasis on generating interpretable, actionable early signals rather than purely exploratory results.

4) Are both adult and pediatric studies allowed?

Yes. The NOFO specifically notes a major focus on first-in-human and other early clinical studies in both adult and pediatric populations.

5) What does "milestone-driven" mean in this program?

This program is structured around clearly defined milestones and go/no-go decision points. The goal is rapid learning that can guide subsequent development, meaning projects are expected to produce concrete results that support a clear decision about whether to proceed to the next development step.

6) What is the award mechanism, and why does it matter?

The award mechanism is a U01 cooperative agreement. In a cooperative agreement, NIH staff typically have substantial scientific and programmatic involvement during the project period. The program design highlights close coordination, milestone tracking, and decision-making aligned with development goals.

7) What kind of data is NIH looking for from early drug trials?

For novel drugs, supported early trials are expected to go beyond symptom change. First-in-human and Phase II-enabling work must include evidence of target engagement, such as demonstrating brain exposure or other indicators that the intervention is reaching and affecting the intended biological target in the central nervous system. Applications are expected to evaluate pharmacologic effects along with basic clinical safety and tolerability, producing the kind of dataset needed to determine readiness for larger Phase II or PoC studies.

8) What does "target engagement" mean in this NOFO?

In this NOFO, target engagement refers to evidence that the investigational intervention is reaching and affecting its intended biological target in humans. For drugs, the NOFO provides examples such as demonstrating brain exposure or other indicators that the target is being engaged within the central nervous system.

9) What is emphasized for Phase II/PoC-style drug studies under this opportunity?

In Phase II/PoC contexts, the NOFO emphasizes measuring the drug's impact on clinically relevant physiological systems using functional measures, while also tracking clinical indicators of effect. The goal is to produce early signals that are interpretable and actionable.

10) Are neuromodulatory devices eligible, and what kinds of device studies are supported?

Yes. The NOFO explicitly supports device-based interventions, including first-in-human studies and early feasibility studies (EFS) of novel neuromodulatory devices.

11) What is NIH expecting from early device studies?

For devices, the expectations are translational and milestone-oriented: demonstrate credible target engagement, characterize safety and tolerability, and generate early evidence related to efficacy.

12) Can a project include combination treatment strategies?

Yes. The NOFO allows device approaches and combination treatment strategies where appropriate.

13) What are the main development risks the NOFO wants projects to address?

Across both drugs and devices, the NOFO aims to quickly build a high-quality early clinical package that answers common downstream blockers, including: whether the mechanism is engaged in humans, whether there is a measurable functional effect consistent with the proposed biology, and whether the risk profile appears acceptable.

14) Why does the NOFO emphasize academic and industry/biotech partnerships?

A defining feature of the NOFO is its emphasis on collaborative partnerships between academic biomedical researchers and biotechnology or industry researchers. The program is designed to move beyond purely academic clinical experimentation and into development-oriented teamwork that can support manufacturing, regulatory planning, clinical operations, and eventual commercialization pathways.

15) What kinds of practical development considerations does NIH appear to care about?

Based on the NOFO description, applications should be positioned to move efficiently along a development pipeline. The NOFO calls out practical requirements such as investigational product handling, device engineering controls, and assembling data packages that later-stage funders and investors typically expect.

16) Who is eligible to apply?

Eligibility is broad within the United States. Eligible applicants include (as listed in the opportunity description): state, county, and local governments; public and private institutions of higher education; federally recognized tribal governments and other tribal organizations; public housing authorities; nonprofits (both 501(c)(3) and non-501(c)(3)); for-profit organizations (other than small businesses); and small businesses. The NOFO also highlights additional eligible categories such as HBCUs, Hispanic-serving institutions, AANAPISIs, Tribal Colleges and Universities, Alaska Native and Native Hawaiian-serving institutions, faith-based or community-based organizations, eligible federal agencies, and U.S. territories or possessions.

17) Are foreign organizations eligible to apply?

No. The NOFO clearly excludes non-U.S. entities: foreign organizations are not eligible to apply, non-domestic components of U.S. organizations are not eligible, and foreign components (as defined by NIH policy) are not allowed.

18) Which federal agency is issuing this opportunity?

The opportunity is issued by the National Institutes of Health (NIH).

19) What is the CFDA (assistance listing) number mentioned?

The listing notes CFDA 93.242 as the activity category associated with this health-related opportunity.

20) When is the closing date?

The original closing date listed for this opportunity is October 15, 2027.

21) Is there an award ceiling or a stated number of expected awards?

Not in the information provided. The listing states that an award ceiling and the expected number of awards are not specified.

22) What is the overall "success" output NIH wants at the end of these studies?

The described end goal is a convincing, development-quality early human dataset that reduces uncertainty and helps determine whether the intervention is ready for the next step (such as larger Phase II or PoC work), supporting progress toward eventual FDA-approved treatment options for psychiatric disorders.