CIAS drug development – is it time for a revolution?

Despite advances in our understanding of the natural history of cognitive impairment associated with schizophrenia (CIAS) – and greater insight into the underlying neurobiology – our best efforts have not delivered any pharmacologic solutions to the clinic. More recent late-stage trial failures have highlighted multiple concerns over the construct of CIAS relative to schizophrenia as a whole, and the challenges and opportunities in measuring outcomes that matter to patients. I believe we need revolution – not evolution – in the way we think about CIAS as a construct and how we develop solutions for it, putting the needs of patients and their carers at the centre: we are treating patients, not domains.

Clinical trials are by their nature only a surrogate for daily practice, but the current approach to assessing cognitive function and patient functionality in CIAS trials is significantly divorced from clinical practice and what patients experience: there is a need for a simpler, more reproducible and patient-relevant way to assess these and their impact. We also need to consider trial entrance criteria, based on learnings from multiple trials. Developing pharmacology for a complex set of deficits related to different brain circuits also remains a challenge: we may need to accept less universal benefits from single agents and should investigate the value of combining pharmacology with cognitive rehabilitation techniques.

During this session, we will debate these issues, and others, and what we need to do to aid the development of therapeutic interventions for the significant patient need that remains.