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New Experimental Medicine Studies: Fast-Fail Trials (FAST)

NAMHC Concept Clearance

Presenter

Bruce Cuthbert, Ph.D.
Director, Division of Adult Translational Research and Treatment Development (DATR)

Goal

This initiative seeks to expeditiously test and analyze novel pharmacological interventions and their molecular and/or clinical targets for treating clinical dimensions of psychopathology associated with traditional psychiatric disorders.

Rationale

Recent breakthroughs in basic science and in the understanding of complex disorders offer promising new opportunities for researchers to pursue and develop novel treatments for those living with mental illnesses. Now is a critical time to take advantage of new breakthroughs and tools. But the paths for treatment discoveries are not clearly marked. Despite the tremendous advances in basic neuroscience and behavioral science that drive our understanding of the mechanisms underlying complex disorders, there is a dearth of new therapeutics in the discovery pipeline.

The overall goal of this initiative is to implement an experimental medicine paradigm of “fast-fail” proof-of-clinical-mechanism (POCM) and proof-of-concept (POC) trials in order to expeditiously test and analyze compounds (i.e., new chemical entities (NCE), re-purposed compounds) and their molecular and/or clinical targets for treating clinical dimensions of psychopathology (e.g., anhedonia, cognitive function, social engagement) associated with traditional psychiatric disorders. NIMH has a strong interest in strategies directed towards ameliorating clinical dimensions of psychopathology embedded in DSM-IV-TR diagnostic entities, but not typically identified as the primary target of current clinical therapeutics.

The initiative will focus on the analyses of novel molecular and clinical targets, engaged by both new and re-purposed compounds. Evaluating potential biomarkers, including receptor occupancy with PET and engagement of relevant brain systems with fMRI, EEG, emotional reactivity, neurocognitive performance, etc., in early phase (Phases I and IIa) clinical trials to demonstrate biological effects could provide information critical to the decision as to whether to proceed further with a specific compound. These types of small trials could prove valuable in de-risking a compound or demonstrating a “fast-fail” for a new target.

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