Notice Number: NOT-MH-18-004

Key Dates
Release Date: November 3, 2017 - RESCINDED

Issued by
National Institute of Mental Health (NIMH)

Purpose

The purpose of this Notice is to inform potential applicants that NIMH will accept mechanistic studies only (as described below), that meet NIH's definition of a clinical trial, in response to PA-18-345, NIH Research Project Grant (Parent R01 Clinical Trial Required) and its reissues or PA-18-344, NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Required) and its reissues. A mechanistic study is designed to understand a biological or behavioral process, the pathophysiology of a disease, or the mechanism of action of an intervention.

NIH defines a clinical trial as A research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes. (NOT-OD-15-015)

NIMH supports hypothesis-driven mechanistic clinical trial studies in basic and/or translational discovery research in healthy human subjects and in the pathobiology, pathophysiology, and psychopathology of mental disorders and in HIV infection of the central nervous system (CNS). The goal is to address basic questions and to interrogate concepts in biology, behavior, and pathophysiology that will provide insight into understanding mental health and mental disorders. Such studies may seek to understand a biological or behavioral process, or the mechanism of action of an intervention for mental disorders. NIMH supports biomarker studies that may provide information about physiological function, target engagement of novel therapeutics, and/or mechanisms of therapeutic responses. The submitted studies are defined as clinical trials (as noted above) but do not seek to establish safety, clinical efficacy, effectiveness, clinical management, and/or implementation of preventive, therapeutic, and services interventions. These latter studies will not be accepted under these FOAs, but applicants instead should seek the appropriate NIMH Clinical Trial FOA (and their subsequent reissuances) under which to submit. The NIMH Clinical Trial FOAs are listed on NIMH’s Clinical Trials Funding Opportunity Announcements Web page.

Examples of types of applications intended to be supported by NIMH under the NIH Parent Clinical Trials R01 and R21 FOAs include, but are not limited to:

• Studies in which a manipulation (physiological or behavioral) is used to answer basic science questions about normal brain function.
• Studies to develop, validate, and/or apply novel measures of brain signaling and circuits contributing to cognition, emotional regulation, and social behavior in healthy humans including, for example, PET, SPECT, and other neuroimaging approaches, as well as biomarkers of physiological processes.
• Studies that use an experimental manipulation (e.g., CNS active drugs, direct neurostimulation or cognitive task activating a specific neural circuit) in order to understand normal functioning or the pathophysiology of a mental disorder, but do not aim to demonstrate clinical improvement.
• Studies that involve the prospective use of efficacious interventions (e.g., biomedical, behavioral, cognitive, other therapeutic approaches), where the intent is to obtain biospecimens (e.g., blood, patient-derived induced pluripotent stem cells) to identify genetic risk associations, novel biomarkers, examine the disease process, or characterize mechanisms of therapeutic response.
• Studies in which an intervention with demonstrated efficacy for that population (e.g., an SSRI, CBT, or ECT for depression) is being studied to understand mechanisms of response, non-response, or risk of adverse effects of the efficacious intervention.
• A clinical research study that administers a standard intervention for its indicated use to control for confounds related to the heterogeneity of treatment response.
• Longitudinal follow-up and assessment of participants from completed clinical trials where there will be no additional recruitment or further treatment of participants.

The following types of clinical trials are not intended to be supported by NIMH under the NIH Parent Clinical Trials R01 and R21 FOAs:

• Studies that do not meet the NIH definition of clinical trial.
• Early-stage trials of novel treatment approaches in humans that are prerequisite to clinical efficacy trials for pharmacological, device, or behavioral intervention development.
• Studies to develop or conduct tests of the clinical efficacy/effectiveness of treatments.
• Studies that have safety, clinical efficacy, clinical management, and/or implementation as its principle aim.

Data Sharing =
In order to support the goal of advancing research through widespread data sharing among researchers, investigators funded under this FOA are expected to share those data via the National Institute of Mental Health Data Archive (NDA; https://data-archive.nimh.nih.gov). Established by the NIMH, NDA is a secure informatics platform for scientific collaboration and data-sharing that enables the effective communication of detailed research data, tools, and supporting documentation. A cost estimation tool for data sharing is available at https://ndct.nimh.nih.gov/preplanning/budget and can be used l when preparing budgets for applications.

Recruitment Reporting
NIMH requires reporting of recruitment milestones for participants in all NIMH extramural-funded clinical research studies proposing to enroll 150 or more subjects per study, and all clinical trials, regardless of size (see https://grants.nih.gov/grants/guide/notice-files/NOT-MH-16-013.html). All NIMH funded mechanistic clinical trials funded under these FOAs must report recruitment milestones, including those with fewer than 150 subjects. This expectation will be stated in the notice of grant award.

Single IRB
For multi-site trials, use of a single IRB is expected. The number of trial sites should be limited to minimize variability of the data.

NIMH strongly encourages applicants to consult with NIMH Program Officials prior to submitting an application with human subjects, to determine which available FOA would best support the proposed research. This is particularly important if there is doubt as to whether or not the submission is determined to be an NIH-defined clinical trial or not, and if found to be a clinical trial, whether it is a mechanistic study as described by NIMH (above).

Inquiries

Please direct all inquiries to:

https://www.nimh.nih.gov/funding/opportunities-announcements/nimh-mechanistic-clinical-trial-contacts.shtml