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NAMHC FAST Workgroup Charge

| Roster |

Background

In September 2012, NIMH anticipates awarding contracts under three RFPs. These contracts will establish clinical trial teams for testing novel compounds in early phase trials for disorders related to the mood and anxiety spectrum (FAST-MAS), the psychotic spectrum (FAST-PS) and the autism spectrum (FAST-AS). Each disorder spectrum will be conceptually aligned with the NIMH Research Domain Criteria Project (RDoC), which intends to accelerate the pace of discovery by targeting fundamental mechanisms that cut across current diagnostic categories (see the Research Domain Criteria (RDoC) page for more details).

The FAST networks will implement an experimental medicine paradigm of ‘fast-fail’ trials to determine the activity of novel and repurposed compounds on their intended molecular or clinical targets. Depending on the data available for the selected compounds, trials may be Phase I or Phase IIa (e.g., First in Human, Proof of Clinical Mechanism or Proof of Concept) to demonstrate target engagement, safety, and early signs of efficacy. Each trial may be single-site or multisite and may focus on healthy subjects or a cohort of patients with pathology across the diagnostic spectrum of the disorder under study. Each trial will be designed to inform a go/no go judgment about whether the intervention warrants further evaluation.

Workgroup Charge

This workgroup is asked to advise the National Advisory Mental Health Council on the most promising molecular targets and compounds for disorders of the mood and anxiety spectrum, the psychotic spectrum and the autism spectrum. Workgroup members may advise council on:

  1. A process to identify and evaluate the most promising molecular targets based on, for example, genetics, gene expression data, and pathway analysis
  2. A process to identify candidate compounds that affect these targets and hold promise for clinical benefit substantiated, for example, by:
    1. Preclinical studies in which target engagement can be related to pharmacodynamic readouts (e.g. biochemical or physiological change) that have a human homologue
    2. Preclinical studies in which target engagement can be related to behavioral readout (e.g. memory dependent tasks) that may have a human analogue
    3. An available method for establishing target engagement of the compound in humans coupled to brain effect (e.g. biochemical readout in CSF or functional brain imaging)
  3. Strategic considerations as to the depth and breadth of targets to explore given the available resources.
  4. Appropriate experimental aims and design considerations for early phase clinical trials of selected compounds. This may include advice on how best to incorporate RDoC-relevant outcome measures.