Structural and construct validity assessment of the schizophrenia cognition rating scale (SCoRS) using data from three international phase 3 randomized controlled trials (CONNEX programme)

Cognitive impairment associated with schizophrenia (CIAS) is a fundamental symptom of the disorder, which significantly affects individuals' daily functioning and overall quality of life. Currently available antipsychotic drugs have little beneficial effect on CIAS, so there remains a significant unmet need to continue development of novel treatment options. Typical assessment of CIAS relies on performance based cognitive tests which have limitations in both application and interpretation. The interview-based Schizophrenia Cognition Rating Scale (SCoRS) was originally designed to facilitate the measurement of CIAS and related functioning as viewed by patients, informants, and interviewers, and has the potential to provide a measure of clinically meaningful changes in cognitive impairment and related functional capacity. This study used confirmatory factor analysis (CFA) to assess the structural validity of the SCoRS Interviewer total score, together with known-groups validity assessment. Using data from a clinical trial of iclepertin in adult patients with schizophrenia, we explored the dimensionality of the SCoRS using various CFA models including single factor, four correlated factor, and bifactor models. Three external reference anchors were used to assess known-groups validity, based on clinician and study partner ratings of disease severity over time. We found that the models support the essential unidimensionality of the SCoRS, while the known-group validity analysis showed that the SCoRS interviewer total score was able to discriminate between severity groups, which supports its use for measuring CIAS in both clinical research and real-world clinical practice.