Notice Number: NOT-NS-19-012

Key Dates
Release Date: November 5, 2018

Issued by
National Institute of Neurological Disorders and Stroke (NINDS)

Purpose

The purpose of this Notice is to announce NINDS's policy for submission of applications to PA-19-055 "NIH Research Project Grant (Parent R01 Clinical Trial Required)." NINDS will only accept applications to the NIH Research Project Grant (Parent R01 Clinical Trial Required) Funding Opportunity Announcement (FOA) and its reissues that propose human mechanistic trials/studies that meet NIH's definition of a clinical trial and that fall within the NINDS research priorities.

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)

NIH defines a mechanistic clinical trial as follows: "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.

NINDS supports hypothesis-driven mechanistic clinical trial studies in basic and/or translational discovery research in healthy human subjects and in the pathobiology, pathophysiology, and neuropathology of neurological disorders. The goal is to address basic questions and to interrogate concepts in biology, behavior, and pathophysiology that will provide insight into understanding neurological disorders. Such studies may seek to understand a biological or behavioral process, or the mechanism of action of an intervention. NINDS 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 answer specific questions about safety, tolerability, clinical efficacy, effectiveness, clinical management, and/or implementation of pharmacologic, behavioral, biologic, surgical, or device (invasive or non-invasive) interventions. preventive, therapeutic, and services interventions. Such designs should be submitted to an NINDS clinical trial-specific funding announcement (listed on the NINDS website at https://www.ninds.nih.gov/Current-Research/Research-Funded-NINDS/Clinical-Research). Applicants are strongly advised to consult with NINDS program staff prior to submitting an application with human subjects to determine the appropriate funding opportunity.

Examples of types of applications intended to be supported by NINDS under the NIH Parent Clinical Trial R01 FOA 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 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 neurological 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 is being studied to understand mechanisms of response, non-response, or risk of adverse effects of the efficacious intervention.

The following types of clinical trials are not intended to be supported by NINDS under the NIH Parent Clinical Trials R01 FOA:

• 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 principal aim.

Resource

• Does your human subjects research study meet the definition of a clinical trial?

Inquiries

Please direct all inquiries to:

Claudia Moy, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9135
Email: moyc@ninds.nih.gov