Exploratory Clinical Trials of Novel Interventions for Mental Disorders (R21/R33) | Apply Online

Frequently Asked Questions (FAQs)

What is the Exploratory Clinical Trials of Novel Interventions for Mental Disorders (R21/R33) opportunity?

This opportunity (Funding Opportunity Number RFA-MH-16-405) is an NIH discretionary grant program that supports early-stage clinical testing of promising new interventions for mental disorders. It is designed to help move interventions from basic science concepts into carefully structured pilot clinical trials.

What is the main purpose of this FOA?

The main purpose is to generate strong, decision-quality evidence that supports clear go/no-go decisions about whether an intervention should advance to further development or larger-scale testing. The FOA is built to produce high scientific value results regardless of whether findings are positive, negative, or null, as long as the study convincingly answers key mechanistic questions.

What does an "experimental therapeutics" approach mean in this announcement?

An "experimental therapeutics" approach means applicants are expected to test more than whether an intervention appears to help. Projects must also test whether the intervention engages and changes a clearly defined therapeutic target that is tied to mechanisms of mental disorders, and then relate that target engagement to functional or clinical outcomes.

Does this FOA require that applicants identify a therapeutic target?

Yes. A central expectation is that applicants define a clear therapeutic target and design the trial to measure it reliably, demonstrate that the intervention changes it in the intended direction, and then connect that target change to meaningful outcomes.

Are negative or null trial results considered useful under this FOA?

Yes. The FOA emphasizes that results should have high scientific value regardless of outcome. A negative or null result is still considered informative if the study convincingly determines whether the target was engaged and whether target engagement relates to functional or clinical change.

What kinds of interventions are considered responsive to this FOA?

A wide range of intervention types may be responsive because the FOA focuses on novelty and mechanism rather than a single modality. Examples listed include behavioral, pharmacological, biologics-based, cognitive, device-based, interpersonal, physiological, and combined or multimodal approaches.

Does the FOA focus on adults, children, or both?

Both. The program explicitly covers adults and children and emphasizes mental disorders broadly rather than restricting to a single diagnosis area.

Is this opportunity limited to one specific mental disorder or diagnosis area?

No. The FOA emphasizes mental disorders broadly and does not restrict the program to a single diagnosis area. The key requirement is that the proposed clinical trial efficiently evaluates a novel intervention through target engagement and linkage to meaningful outcomes.

What grant mechanism does this FOA use?

It uses a phased, milestone-driven R21/R33 mechanism. The first phase (R21) supports early, feasibility-focused work with a strong emphasis on validating target engagement. The second phase (R33) supports the next step of linking target changes to functional or clinical effects.

How long can the R21 phase last, and what is it intended to accomplish?

The R21 phase can provide up to two years of support. It is intended to support preliminary testing focused on establishing feasibility and, critically, validating that the intervention engages its intended therapeutic target. This includes demonstrating the ability to measure the target reliably and showing the intervention changes it in the intended direction.

How does a project transition from R21 to R33?

The transition is milestone-driven. If the R21 phase meets predefined milestones, the project may transition to the R33 phase for additional support.

How long can the R33 phase last, and what is it intended to accomplish?

The R33 phase can provide up to three additional years of support. It is intended to link changes in the intervention target to functional or clinical effects, strengthening the causal chain between mechanism (target engagement) and patient-relevant outcomes.

Why is the phased, milestone-driven design used?

The phased design is meant to reduce wasted time and resources by advancing projects only when early evidence supports continued investment. It helps ensure that larger or longer testing is pursued only after target engagement and early milestones are achieved.

What is the funding instrument type and activity category for this opportunity?

The funding instrument type is a Grant, and the funding activity category is Health.

What CFDA number is associated with this opportunity?

The listing is under CFDA 93.242 (Mental Health Research Grants).

Is cost sharing or matching required?

No. The FOA indicates there is no cost sharing or matching requirement.

How much total funding is estimated, and is there an award ceiling?

The provided record lists an estimated total funding amount of $4,000,000. It also lists an award ceiling of $200,000 in the source information.

Who is eligible to apply?

A broad range of applicants are eligible, including public and private institutions of higher education; nonprofit organizations (including 501(c)(3) and other nonprofit categories); for-profit organizations (including small businesses and other for-profits); and multiple levels of government entities (state, county, city/township, special district governments), as well as public housing authorities and tribal governments and organizations.

Does the eligibility language explicitly include certain institution types and communities?

Yes. The eligibility language highlights inclusion of many institution types and communities, including HBCUs, Hispanic-serving institutions, AANAPISIs, tribally controlled colleges and universities, faith-based or community-based organizations, U.S. territories or possessions, and non-U.S. (foreign) entities and regional organizations, among others.

What key dates are listed for this opportunity?

The provided record includes a posted date of March 30, 2015; a creation date of April 23, 2015; an original closing date of October 14, 2016; and an archive date of May 23, 2015. The listing also shows a "current closing date" of April 23, 2015.

Is this opportunity likely still open?

The record shows an archive date and also contains conflicting date signals (including a "current closing date" of April 23, 2015). Based on the information provided, it appears to reflect an archived snapshot, and applicants would need to confirm the historical status and any reissues or related active opportunities through NIH.

Where can the full announcement be found?

The full announcement was linked through the NIH grants guide at: http://grants.nih.gov/grants/guide/rfa-files/RFA-MH-16-405.html

Who is listed as the contact for technical or access issues?

The contact information provided is directed to the NIH Office of Extramural Research (OER) webmaster emails for technical access or linking problems.

What kind of applicant or project is this FOA aimed at in practical terms?

In practical terms, it is aimed at investigators with a scientifically grounded, mechanistically informed intervention idea who want to run a tightly designed early clinical trial that can credibly answer whether the intervention engages the target and whether target change plausibly drives improvement in symptoms or functioning.

What makes a clinical trial design a good fit for this FOA?

Based on the description provided, a good fit is a trial designed to efficiently evaluate a novel intervention by (1) demonstrating reliable measurement and engagement of a clearly defined therapeutic target and (2) connecting target change to meaningful functional or clinical outcomes, supporting a go/no-go decision about next development steps.