Building in vivo Preclinical Assays of Circuit Engagement for Application in Therapeutic Development (R01 Clinical Trial Not Allowed) | RFA MH 19 235

Frequently Asked Questions (FAQs)

What is the funding opportunity called?

The opportunity is titled "Building in vivo Preclinical Assays of Circuit Engagement for Application in Therapeutic Development (R01 Clinical Trial Not Allowed)."

Which agency is offering this grant?

This is a National Institutes of Health (NIH) funding opportunity.

What is the FOA number and CFDA listing provided?

The FOA number is RFA-MH-19-235 and the CFDA number listed is 93.242.

What is the main purpose of this funding opportunity?

The purpose is to strengthen early, preclinical mental health treatment development by improving how potential therapies are screened in animals. It emphasizes building and refining in vivo neurophysiological and behavioral assays that indicate whether a therapeutic target or candidate treatment is engaging relevant brain circuits.

What does "circuit engagement" mean in the context of this FOA?

"Circuit engagement" refers to readouts that reflect whether intended neural systems are being modulated as hypothesized. The FOA emphasizes measures closer to underlying neural mechanisms implicated in mental illnesses, rather than relying only on broad behavioral outcomes or indirect readouts.

What types of assays or measures does the FOA emphasize?

The FOA emphasizes in vivo neurophysiological and behavioral assays in animals. Examples of circuit-relevant processes mentioned include neural activity patterns, network dynamics, and behavior that is tightly linked to specific circuitry.

Is the focus on basic neuroscience discovery or tool-building for therapeutic development?

The emphasis is on producing tools that can be used repeatedly and reliably for early screening in therapeutic development. The intent is not simply to describe interesting neuroscience phenomena, but to develop assays that help test whether manipulating a target or administering a candidate therapy produces the desired effect on brain circuitry relevant to mental illness.

How are applicants expected to choose what to measure in their assays?

Applicants are expected to build on existing knowledge from systems neurobiology and clinical neuroscience to select circuit-relevant processes, then identify, optimize, and evaluate animal-based measures that can serve as surrogate markers of clinically meaningful neural processes.

What is meant by "surrogate markers" in this program?

In this FOA, surrogate markers are animal-based measures intended to stand in for neural processes that matter clinically. The goal is for these measures to provide mechanistically grounded signals that are more informative for therapeutic screening and target validation.

What kinds of decisions are these assays intended to support?

The assays are intended to make animal data more scientifically valuable and interpretable for go/no-go decisions and for prioritizing candidates before expensive downstream development.

Are projects required to be translational?

Yes, the work is framed with a translational trajectory. Although the supported work is explicitly centered on animals, it is described as a first step toward assays that can ultimately be adapted across species and carried forward toward human evaluation.

Does this R01 include human studies?

Based on the information provided, the R01 is devoted to building and validating animal measures. The announcement describes later efforts that would examine whether the same assays perform coherently in preclinical species and healthy humans, but that cross-species human bridging work is referenced as a related effort under a different NIH mechanism.

Is a clinical trial allowed under this FOA?

No. This opportunity explicitly states "Clinical Trial Not Allowed."

What grant mechanism is being used?

This is an NIH R01 mechanism and is described as a discretionary NIH grant.

Who is the intended scientific audience for this program?

The intended audience includes basic and translational neuroscientists focused on improving the efficiency of the therapeutic development pipeline for mental illnesses by advancing measures of circuit engagement for early phase target validation and therapeutic screening.

What is the primary deliverable expected from funded projects?

The deliverable is a stronger preclinical toolkit: in vivo assays that are mechanistically grounded, reliable for repeated use, more predictive, and more aligned with clinically meaningful neural processes than many traditional preclinical endpoints.

What kinds of organizations are eligible to apply?

The opportunity lists a broad range of eligible applicants, including state, county, city/township, and special district governments; independent school districts; public and private institutions of higher education; federally recognized Native American tribal governments and other tribal organizations; public housing authorities/Indian housing authorities; nonprofits (with or without 501(c)(3) status); for-profit organizations (other than small businesses); and small businesses.

Are mission-focused and community-based institutions included in eligibility?

Yes. The eligibility list notes a variety of mission- and community-focused institutions and organizations, including Alaska Native and Native Hawaiian Serving Institutions, AANAPISI institutions, Hispanic-serving institutions, Historically Black Colleges and Universities, Tribally Controlled Colleges and Universities, and faith-based or community-based organizations.

Are U.S. territories or possessions eligible?

Yes. U.S. territories or possessions are listed among eligible applicants.

Are foreign (non-U.S.) organizations eligible to apply?

Yes. The eligibility list includes non-U.S. entities (foreign organizations) as well as regional organizations.

Does the FOA specify an award ceiling or the expected number of awards?

No. The provided source data indicates that the award ceiling and expected award counts are not specified.

When was the FOA created and what was the original closing date?

The FOA was created on 2018-10-30, and the original closing date listed is 2019-02-04.

How does this FOA relate to other NIH efforts mentioned?

The announcement describes this FOA as a precursor to later efforts that would test whether the same assays perform coherently across species, including preclinical species and healthy humans. It references a related NIH mechanism (PAR-16-065, UG3/UH3) focused on bridging translational gaps.

What makes this FOA different from traditional preclinical endpoints?

Rather than relying mainly on broad behavioral outcomes or indirect readouts, this FOA emphasizes measures that are closer to underlying neural mechanisms and specifically designed to indicate whether relevant brain circuits are being engaged by a target manipulation or candidate therapy.