Optimizing early Go/No Go decisions in CNS drug development.

Go/No Go decisions concerning development of any single compound determine investment in increasingly costly studies from Phases I-III. Such decisions are problematic for CNS drug development where the variety of molecular targets in the brain have stimulated decades of studies without major therapeutic advances. Many costly studies do not even yield interpretable results as to whether the mechanism being pursued has therapeutic potential. Therefore, both industry and the public sector have implemented a decision making strategy based on whether a compound can test a molecular hypothesis of drug action. One requires, at a minimum, compelling evidence in humans that a compound both interacts with its presumed molecular targets in brain and ideally documents a CNS functional consequence of the interaction prior to efficacy studies. This strategy will much more quickly rule out ineffective mechanisms although it does not address the problem of poorly predictive models of novel CNS drug efficacy.