NIMH Acceptance of Clinical Trial Applications under the Parent R01 and R21 Clinical Trial Required, or Basic Experimental Studies Involving Humans (BESH) Announcements is Limited to Mechanistic Clinical Trials

Notice Number: NOT-MH-19-006

Key Dates
Release Date: December 21, 2018

Related Announcements

PA-19-055

PA-19-091

PA-18-345

PA-19-054

PA-19-092

PA-19-090

PA-19-084

PA-19-086

PA-19-087

PA-19-088

NOT-MH-18-004

Issued by
National Institute of Mental Health (NIMH)

Purpose

The purpose of this Notice is to inform potential applicants that NIMH acceptance of NIH-defined clinical trials in response to PA-19-055, NIH Research Project Grant (Parent R01 Clinical Trial Required); PA-19-054, NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Required); PA-19-091, (Parent R01 Basic Experimental Studies with Humans Required, (BESH)) and PA-19-092, (Parent R21 Basic Experimental Studies with Humans Required, (BESH)), as well as all reissuances of these announcements, is limited to mechanistic clinical trials.

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).

A mechanistic clinical trial is designed to understand a biological or behavioral process, the pathophysiology of a disease, biomarkers for a disease or response to treatment, or the mechanism of action of an intervention. It is not designed to test the safety or demonstrate the efficacy/effectiveness of an intervention.

With respect to the BESH funding opportunities, NIH defines basic research consistent with the definition of basic research in federal code, “the systematic study directed toward greater knowledge or understanding of the fundamental aspects of phenomena and of observable facts without specific applications towards processes or products in mind.” (32 CFR 272.3).

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.

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

  • 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.

Examples of types of mechanistic studies intended to be supported by NIMH under the Parent R01 and R21 Basic Experimental Studies with humans required (BESH) 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.

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

  • Studies that do not meet the NIH definition of clinical trial.
  • Early-stage trials of novel intervention 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 preventive, therapeutic, or services interventions.
  • Studies that have safety, clinical efficacy, clinical management, and/or implementation as a primary aim.

For more information see the NIMH Clinical Trials FOAs web page.

NIMH is also accepting applications under the following BESH career announcements: PA-19-090 NIH Pathway to Independence Award (Parent K99/R00 Independent Basic Experimental Studies with Humans Required); PA-19-084 Mentored Research Scientist Development Award (Parent K01 Independent Basic Experimental Studies with Humans Required); PA-19-086 Mentored Clinical Scientist Research Career Development Award (Parent K08 Independent Basic Experimental Studies with Humans Required); PA-19-087 Mentored Patient-Oriented Research Career Development Award (Parent K23 Independent Basic Experimental Studies with Humans Required); PA-19-088 Midcareer Investigator Award in Patient-Oriented Research (Parent K24 Independent Basic Experimental Studies with Humans Required). See general information on NIMH Career Development Programs.

Data Sharing

In order to support the goal of advancing research through widespread data sharing among researchers, investigators funded under these FOAs 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 when preparing budgets for applications.The NIH is delaying the enforcement of registration and results reporting for trials supported under the BESH FOAs until September 2019 as noted in NOT-OD-18-212.

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 using the same protocol and involving non-exempt human subjects research, use of a single IRB is expected. For more details see: NOT-OD-16-094

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:

NIMH Clinical Trial Contacts