Derisking Psychiatric Drug Development: The NIMH's Fast Fail Program, A Novel Precompetitive Model.

The lack of success of psychiatric drug research and development has increased attention on the use of precompetitive models of early stage clinical drug development, whereby foundations, companies and academic researchers led by NIH, work together to advance a pipeline of potential novel therapeutics. This commentary presents an example of such an approach through which the National Institute of Mental Health contracted a network of academic researchers to work with other stakeholders to investigate AZD7325, a drug targeting the GABA-A α2/α3 receptor subtype, in young adult subjects with autism spectrum disorder using an experimental medicine approach. Instead of relying on traditional clinical measures, electroencephalography was used to evaluate pharmacodynamic responses and was established as the primary outcome measure, in order to objectively identify dose ranges that can modulate central nervous system activity in the absence of significant side effects. Many trial considerations and “lessons learned” were identified through the process of setting up and performing the trial. These considerations are important to present to the research community more broadly, to emphasize what processes and resources are needed to integrate pharmacodynamics measures into multisite trials in research areas which have traditionally relied on clinical rating scales alone. The goal is to design and implement studies that will provide sufficient objective data of brain effects to make go/no-go decisions to clinical efficacy studies in which one is confident that the underlying mechanistic hypothesis of drug action is being tested. We here provide a real life example of what is required to execute this strategy.