Psychometric evaluation of the patient-reported experience of cognitive impairment in schizophrenia (PRECIS) scale.

BACKGROUND: Cognitive impairment associated with schizophrenia (CIAS) represents a distinct, persistent, and core group of schizophrenia symptoms. Cognitive symptoms have been shown to have an impact on quality of life. There are several published CIAS measures, but none based on direct patient self-report. It is important to capture the patient's perspective to supplement performancebased outcome measures of cognition to provide a complete picture of the patient's experience. This paper describes additional validation work on the Patient-Reported Experience of Cognitive Impairment in Schizophrenia (PRECIS) instrument. METHODS: Data from two large, international, pharmaceutical clinical trials in medically and psychiatrically stable English-speaking patients with schizophrenia and 88 healthy controls were analyzed. An exploratory factor analysis (EFA) was conducted in one trial (n = 215), using the original 35-item PRECIS. The factor structure suggested by EFA was further evaluated using item response theory (IRT; Samejima's graded response model), and tested using confirmatory factor analysis (CFA). Both EFA and CFA results were tested in a second trial with similar inclusion/exclusion characteristics (n = 410). Additional statistical properties were evaluated in healthy controls. RESULTS: EFA suggested that the best solution after item reduction suggested a factor structure of 6 factors based on 26 items (memory, communication, self-control, executive function, attention, sharpness of thought), supporting a total score, with an additional 2-item bother score (28 items in all). IRT analysis indicated the items were well-ordered within each domain. The CFA demonstrated excellent model fit, accounting for 69% of the variance. The statistical properties of the 28-item version of the PRECIS were confirmed in the second trial. Evidence for internal consistency and test-retest reliability was robust. Known-groups validity was supported by comparison of healthy controls with patients with schizophrenia. Correlations indicated moderate associations between PRECIS and functioning instruments like the Schizophrenia Cognition Rating Scale (SCoRS), but weak correlations with performance-based outcomes like MATRICS Consensus Cognitive Battery (MCCB). DISCUSSION: Using two clinical trial samples, we identified a robust factor structure for the PRECIS and were able to replicate it in the second sample. Evaluation of the meaningful score difference (MSD) should be repeated in future studies, as these samples did not show enough change for it to be evaluated. CONCLUSIONS: This analysis provides strong evidence for the reliability and validity of the PRECIS, a 28-item, patient-reported instrument to assess cognitive impairment associated with schizophrenia. The correlation with functioning and the weak correlation with performance on cognitive tasks suggests that patient reports of cognitive impairment measure a unique aspect of patient experience.

Societal Utilities for Cognitive Impairment in Schizophrenia: Developing a Preference-Based Scoring Algorithm Based on the Schizophrenia Cognition Rating Scale.

INTRODUCTION: Loss of cognitive function is a common feature in schizophrenia. However, generic measures of health-related quality of life favored by decision-makers, such as the EQ-5D, are not designed to detect changes in cognitive function. We report the valuation of the Schizophrenia Cognition Rating Scale (SCoRS), a schizophrenia-specific measure of cognitive impairment. METHODS: Expert opinion and psychometric analysis of the SCoRS from clinical trial data was undertaken to select 5 key items from the measure. These items were combined orthogonally to develop health-state vignettes. Vignettes were valued using composite time trade-off (cTTO) in one-on-one video calls. Several econometric models were fitted to the data to estimate disutilities. Performance of EQ-5D- and SCoRS-based utilities were compared in the trial data. RESULTS: The SCoRS items selected for the valuation study represented attention, learning, processing speed, social cognition and memory. Four hundred respondents participated in the valuation study. The best observed health state was valued at 0.855 [standard deviation (SD) = 0.179] and the worst at 0.152 (SD = 0.575). At the most severe levels, 'social cognition' received the largest disutility followed by 'learning' and 'memory'. The final model to estimate utilities had 15 parameters. SCoRS-based utilities were sensitive to change in cognition, but the EQ-5D was not. CONCLUSION: It is feasible to value different dimensions of cognition separately using a validated instrument for proxy assessment. The resulting utilities indicate loss of quality of life due to reduced cognitive functioning.

The relationship between cognition and functioning in schizophrenia: A semi-systematic review.

In schizophrenia, impairments in neurocognition (NC) and social cognition (SC) are associated with reduced functional capacity (FC) and poor real-world functioning (RWF). In this semi-systematic review, we examined this association across a range of research questions. We conducted a systematic search in Embase and MEDLINE from 2005 to 2019, and conducted additional pragmatic searches. After screening of titles, abstracts and full-texts, we included 564 citations, of which 44 (26 primary studies, 15 systematic reviews and 3 narrative reviews) were prioritized for reporting. Both NC and SC were significantly associated with functioning, with slightly stronger association for SC. Effect sizes were generally larger for FC than for RWF. NC showed stronger associations with occupational functioning and independent living, and SC with social functioning. Baseline cognition predicted long-term RWF up to 20 years of follow-up, though long-term data were limited for SC. Cognitive remediation improved RWF functioning, especially when it was combined with psychosocial rehabilitation. SC mediated the relationship of NC with functioning. Negative symptoms appeared to mediate and moderate the association of cognition with functioning. Other factors involved included severity of cognitive dysfunction, metacognition, depression and choice of RWF instrument. We discuss potential implications for studies of pharmacological cognitive interventions in schizophrenia - the relevance of both NC and SC, the advantage of adjunctive psychosocial rehabilitation, the role of relevant moderating and mediating variables, and the challenges with RWF instrument selection. Successful cognitive interventions could allow patients with schizophrenia to improve their potential for community functioning.

Health-related Quality of Life in the Phase III LUME-Colon 1 Study: Comparison and Interpretation of Results From EORTC QLQ-C30 Analyses.

INTRODUCTION: We used European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) data from the LUME-Colon 1 study to illustrate different methods of statistical analysis for health-related quality of life (HRQoL), and compared the results. PATIENTS AND METHODS: Patients were randomized 1:1 to receive nintedanib 200 mg twice daily plus best supportive care (n = 386) or matched placebo plus best supportive care (n = 382). Five methods (mean treatment difference averaged over time, using a mixed-effects growth curve model; mixed-effects models for repeated measurements (MMRM); time-to-deterioration (TTD); status change; and responder analysis) were used to analyze EORTC QLQ-C30 global health status (GHS)/QoL and scores from functional scales. RESULTS: Overall, GHS/QoL and physical functioning deteriorated over time. Mean treatment difference slightly favored nintedanib over placebo for physical functioning (adjusted mean, 2.66; 95% confidence interval [CI], 0.97-4.34) and social functioning (adjusted mean, 2.62; 95% CI, 0.66-4.47). GHS/QoL was numerically better with nintedanib versus placebo (adjusted mean, 1.61; 95% CI, -0.004 to 3.27). MMRM analysis had similar results, with better physical functioning in the nintedanib group at all timepoints. There was no significant delay in GHS/QoL deterioration (10%) and physical functioning (16%) with nintedanib versus placebo (TTD analysis). Status change analysis showed a higher proportion of patients with markedly improved GHS/QoL and physical functioning in the nintedanib versus placebo groups. Responder analysis showed a similar, less pronounced pattern. CONCLUSION: Analyses of EORTC QLQ-C30 data showed that HRQoL was not impaired by treatment with nintedanib versus placebo. Analysis and interpretation of HRQoL endpoints should consider symptom type and severity and course of disease.

Nintedanib plus docetaxel as second-line therapy in patients with non-small-cell lung cancer of adenocarcinoma histology: a network meta-analysis vs new therapeutic options.

PATIENTS & METHODS: We provide an update to a network meta-analysis evaluating the relative efficacy of nintedanib + docetaxel versus other second-line agents in adenocarcinoma histology non-small-cell lung cancer. RESULTS: Overall similarity of nintedanib + docetaxel versus ramucirumab + docetaxel, and versus nivolumab. Comparing nintedanib + docetaxel with nivolumab, hazards ratio (HR) of overall survival and progression-free survival (PFS) pointed in opposite directions (overall survival: HR: 1.20 [95% credible interval: 0.92-1.58]; PFS: HR: 0.91 [0.68-1.21]). Exploratory subgroup analysis indicated superiority of nivolumab in high PD-L1 expression level subgroups; results were more favorable for nintedanib in all subgroups with low (<1%, <5%, <10%) PD-L1 expression levels - in particular, with regard to PFS. CONCLUSION: Results demonstrated similar efficacy of nintedanib + docetaxel compared with the new therapeutic options ramucirumab + docetaxel and nivolumab, with potential differences in subgroups according to PD-L1 expression level.

Treatment of Parkinson's disease: a survey of patients and neurologists.

BACKGROUND: The treatment of Parkinson's disease (PD) is complex and highly individual. The choice between available treatment options depends on clinical characteristics such as the patient's age, disease severity and presence of comorbidities, lifestyle characteristics and preferences, costs of different medications and awareness and perception of available treatment options, and education of the treating physician. The impact of PD treatment regimens on patients' health-related quality of life (QOL) is also an important healthcare feature. The objective of the present study was to assess treatment options, treatment satisfaction and opinions about treatment improvements in patients with PD and neurologists treating the disease. METHODS: Two surveys using face-to-face interviews and an additional phone survey were carried out in the US and five European countries (France, Germany, Italy, Spain and the UK). Patients with early and advanced stages of PD were included. To participate in the neurologist survey, neurologists were required to personally treat ten or more PD patients per month, including both early and advanced stage patients. Interviews consisted of a mix of closed and open-ended questions; some of these questions involved show cards. RESULTS: Of the 500 patients who were surveyed, 49% had early and 51% had advanced PD. Early-stage PD patients, both in the US and Europe, take a mean of 3.2 tablets daily of PD-medication. In contrast, the mean daily tablet load of PD medication is much higher for advanced-stage patients (9.9 and 8.4 tablets in the US and Europe, respectively). Tablet load was perceived as a major problem; the majority of patients wished to see improvements regarding daily medication intake and expressed interest in other delivery systems such as patches. Overall, patients rated their treatment with a score of 6.6 points (6.7 for early-stage and 6.6 for advanced-stage patients) [scale of 1-10; 10 being highest]. Physicians (n = 592) were satisfied with a number of current PD medications and assumed they improve the QOL of the patients. They regarded efficacy and safety as the most important features for the improvement of PD medication. CONCLUSION: Further research is needed into PD treatment options not only for symptom alleviation but for better delivery systems that could improve compliance and QOL for patients with PD. Treatment guidelines need to incorporate QOL aspects and general communication between the health professional and the patient.