Psychometric Validation of a Novel PRO Measure for Assessing Patient-reported Experience of Cognitive Impairment in Schizophrenia (PRECIS)

Abstract Background Cognitive impairment associated with schizophrenia (CIAS) can be a distressing feature that contributes to the burden of the disorder, as well as being a strong predictor of functional impairment. To fully assess the burden to patients living with this illness, there is a need to develop a specific measure of patient-reported outcomes (PROs). Methods Following initial development of the Patient-Reported Experience of Cognitive Impairment in Schizophrenia (PRECIS) instrument, the domain structure, reliability (inter-item consistency and test-retest reliability), and validity (discriminant validity, divergent, and convergent validity) of the tool were assessed in patients (aged 18–55 years) with CIAS participating in a 12-week, Phase II, randomized, double-blind, placebo-controlled study to evaluate the efficacy, safety, and tolerability of BI 409306. Healthy control subjects were recruited separately. The PRECIS instrument was completed at baseline, Week 6, Week 9, and Week 12. Results The questionnaire responses of 410 patients with schizophrenia and 88 control subjects were compared. Of the original 35 items included in the draft PRECIS instrument, 11 were eliminated due to poor performance against pre-defined criteria, resulting in a 24-item questionnaire. In confirmatory factor analysis, the 24 items loaded well onto 5 domains (Attention, Memory, Executive Function, Communication, and Bother). The revised 24-item PRECIS instrument demonstrated adequate discriminant validity between patient and control groups in each of the 5 domains (p<0.0001), convergent validity as shown by a significant correlation between PRECIS scores and the Schizophrenia Cognition Rating Scale (SCoRS; p<0.0001), good internal consistency (Cronbach’s alpha score: 0.942), and adequate test-retest reliability (intra-class correlation coefficient [ICC]: 0.78). A simplified, user-friendly scoring method was identified, which assigned scores to each of the 5 domains using a 5-category Likert scale. Conclusions PRECIS is a novel self-completed sensitive instrument designed to measure the subjective experience of cognitive impairment in patients with schizophrenia. The test development process included patient input, perceptions, and feedback, and strong evidence for the validity and reliability of the instrument was demonstrated. The scale provides a patient-based perspective to complement existing objective measures of cognition and serves to define key patient-based endpoints for use in future clinical studies.