Abstract
Cognitive impairment is a core feature and leading cause of functional disability in schizophrenia and other neuropsychiatric disorders. The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative in the early 2000s marked a pivotal moment for drug development, establishing consensus on methodology for treatment studies, including assessment strategies and trial designs, for cognitive impairment associated with schizophrenia (CIAS). Despite extensive industry-sponsored and academic drug development efforts over the last 2 decades using these strategies no pharmacological treatments have been approved for CIAS. Drawing on pharmaceutical industry experience and scientific developments since the MATRICS initiative, we review lessons learned about the practical and operational complexities of conducting large-scale CIAS clinical trials. Based on this collective experience, we identify elements of the MATRICS guidelines that may warrant reconsideration and suggest some new approaches to streamline the drug development pathway, without weakening standards for evidence. Our goal is to initiate an open exchange among all stakeholders about possible enhancements to drug development methodology that optimize our ability to develop new treatments for cognitive impairment in schizophrenia and other neuropsychiatric disorders.