First in Human and Early Stage Clinical Trials of Novel Investigational Drugs or Devices for Psychiatric Disorders (U01 Clinical Trial Required) | PAR 21 133

FAQs: NIH PAR-21-133 (U01) Early-Stage Clinical Trials for Psychiatric Drugs and Neuromodulatory Devices

What is PAR-21-133 trying to support?

PAR-21-133 supports milestone-driven, early stage clinical trials that test new investigational drugs and neuromodulatory devices for psychiatric disorders, particularly where current treatments are not adequate. The goal is practical and translational: produce key human data that can reduce development risk ("de-risk") and help a promising concept become ready for follow-on investment, larger trials, and potential FDA-approved treatments.

What funding mechanism does this opportunity use?

This opportunity uses the NIH cooperative agreement mechanism (U01). Under a cooperative agreement, NIH typically has substantial scientific involvement during the project, and the work is organized around clear milestones and go/no-go decision points.

What does "milestone-driven" mean in this FOA?

"Milestone-driven" means the project is expected to include clear deliverables and decision points, often described as go/no-go criteria. The intent is rapid learning and structured progress, rather than open-ended exploratory work.

What types of studies are in scope for investigational drugs?

For drugs, the FOA is centered on first-in-human (FIH) and early Phase II work, including Phase II or proof-of-concept studies in psychiatric populations when appropriate. These studies are expected to cover safety and tolerability along with pharmacological effects and mechanistic evidence.

What types of studies are in scope for neuromodulatory devices?

For devices, the FOA supports first-in-human studies plus early feasibility studies (EFS) for novel neuromodulatory technologies. These studies should prioritize safety and tolerability and also evaluate target engagement and early signals of efficacy.

Is this FOA limited to symptom-change outcomes?

No. For novel drugs in particular, the FOA expects more than symptom change. Applicants are expected to demonstrate target engagement and provide evidence that the intervention is reaching and affecting the intended biological target.

What does the FOA mean by "target engagement"?

Target engagement refers to evidence that the investigational drug or device is acting on the intended biological target. For drugs, the FOA notes that this should include evidence tied to brain exposure or other convincing measures showing the intervention reaches and affects the target.

What basic clinical development elements are expected for early drug studies?

Early drug studies are expected to characterize pharmacological effects and address core clinical development needs such as safety and tolerability, alongside target engagement.

What is expected in Phase II or proof-of-concept drug studies under this FOA?

For Phase II or proof-of-concept drug studies, the FOA expects evaluation of impact on clinically relevant physiological systems using functional measures, alongside clinical indicators of effect. The overall expectation is a clear connection between mechanism and outcomes.

What kinds of endpoints does the FOA emphasize for Phase II/proof-of-concept drug trials?

The FOA emphasizes endpoints that connect mechanism to outcomes: objective or functionally meaningful measures reflecting the biological system the drug is intended to influence, paired with clinical indicators suggesting patients may be improving in clinically meaningful ways.

Does the same "mechanism-to-outcomes" idea apply to devices?

Yes. Device projects are expected to evaluate target engagement and early signals of efficacy while prioritizing safety and tolerability, consistent with early feasibility work for neuromodulatory technologies.

What is the overall purpose of generating early human data in this program?

The purpose is to generate key human data that reduces scientific and development risk, making a promising drug or device concept more attractive for follow-on investment and larger trials that could ultimately support FDA-approved treatments.

Does the FOA encourage partnerships with industry?

Yes. A notable feature of this FOA is a strong push for collaboration between academic/biomedical researchers and biotechnology or industry partners to help prevent early development from stalling and to improve readiness for later-stage development.

Why does the FOA emphasize academic-industry collaboration?

The FOA points to common barriers in early psychiatric drug and device development that require coordinated expertise, including clinical trial execution, regulatory planning, manufacturing or device engineering, and commercialization pathways. Structured partnerships are encouraged to speed translation.

Who is eligible to apply?

The opportunity is open to a broad range of U.S. applicant organizations, including state and local governments, public and private institutions of higher education, nonprofits (with or without 501(c)(3) status), for-profit organizations (other than small businesses), small businesses, and eligible tribal governments and tribal organizations.

Are mission-focused and community-based institutions eligible?

Yes. The FOA explicitly highlights eligibility for several mission-focused institution types and community-based entities, including Historically Black Colleges and Universities (HBCUs), Hispanic-serving institutions, tribally controlled colleges and universities (TCCUs), Alaska Native and Native Hawaiian serving institutions, and faith-based or community-based organizations, among others.

Are foreign organizations or foreign components allowed?

No. Non-U.S. entities and foreign institutions are not eligible to apply. Non-U.S. components of U.S. organizations are not eligible, and foreign components are not allowed under NIH policy for this announcement.

What is the CFDA number and category for this opportunity?

The opportunity is listed as an NIH discretionary grant in the health category with CFDA 93.242.

When was this opportunity created and what closing date is listed?

The opportunity was created on 2021-03-02 and lists an original closing date of 2024-10-15.

Does the provided excerpt list an award ceiling or number of awards?

No. The excerpt does not specify an award ceiling or the expected number of awards.

What kinds of projects does the "de-risking" emphasis suggest NIH is looking for?

Based on the description, the program is geared toward well-structured projects with clear deliverables, rigorous early clinical endpoints (including target engagement), and a credible plan to move the intervention toward later-stage development if the data support it.

Is the FOA focused only on drugs, or only on devices?

It supports both: investigational drugs and neuromodulatory devices for psychiatric disorders, with study expectations tailored to early clinical stages for each modality (FIH/early Phase II for drugs; FIH/EFS for devices).

What is NIH's anticipated role during the project?

Because this is a U01 cooperative agreement, NIH typically has substantial scientific involvement, with an emphasis on milestones, go/no-go decision points, and rapid learning during the project.