Toward the use of proxy reports for estimating long-term patient-reported outcomes in multiple sclerosis.

BACKGROUND: Assessment of disease impact in multiple sclerosis (MS) is usually driven by information obtained directly from patients using patient-reported outcomes. However, when patients' response in longitudinal studies is less reliable or missing, proxy respondents may be used. OBJECTIVE: The objective of this paper is to evaluate whether long-term patient scores can be reliably estimated using scores obtained from proxies. METHODS: Baseline, six-month and two-year data were collected from 155 patients and proxies on the physical scale of the Multiple Sclerosis Impact Scale (MSIS-29). Linear regression analyses were performed with the patient two-year scores as outcome, proxy two-year scores as predictor and other variables that could contribute to a better prediction of the patient follow-up score. RESULTS: The patient follow-up score could be predicted rather accurately (R(2) = 0.74) using the patient baseline score and the proxy follow-up score. The correlation between observed and predicted scores was 0.86. The model performed well in different follow-up durations and even better in an external cohort. CONCLUSION: A simple model of a constant value (intercept), the patient baseline score and the proxy follow-up score can predict patients' follow-up score on the physical impact of MS.

Validation and interpretation of the Dutch version of the Multiple Sclerosis Neuropsychological Screening Questionnaire.

BACKGROUND: The Multiple Sclerosis Neuropsychological Screening Questionnaire (MSNQ) was developed for screening of MS patients at risk for cognitive impairment with a patient self-report (MSNQ-P) and an informant version (MSNQ-I). The objective of this study was to validate the Dutch versions and determine their interpretability. METHODS: The MSNQ was completed by 121 MS patients and their partners (informants). We investigated the factor structure, internal consistency and construct validity. Interrater reliability between MNSQ-P and MSNQ-I was investigated with the intraclass correlation coefficient (ICC) and Cohen's kappa. For interpretability of both MSNQ versions we calculated sensitivity, specificity and cut-off scores. Receiver operating characteristic (ROC) curves with related area under the curve (AUC) were used to evaluate the added value of combining both versions. RESULTS: We found a unidimensional factor structure. Cronbach's alphas were 0.93 and 0.94 for MSNQ-P and MSNQ-I, respectively. The ICC was 0.59 and kappas were ≤0.50. No cut-off score could be defined for the MSNQ-P because of low sensitivity. For the MSNQ-I, sensitivity was 0.75 and specificity 0.71 (AUC 0.80). The cut-off score was 21. ROC curve analyses showed no added value of the MSNQ-P when used in combination with the MSNQ-I. CONCLUSIONS: The MSNQ-I is preferred over the MSNQ-P to screen MS patients for cognitive impairment.

The size of the treatment effect: do patients and proxies agree?

BACKGROUND: This study examined whether MS patients and proxy respondents agreed on change in disease impact, which was induced by treatment. This may be of interest in situations when patients suffer from limitations that interfere with reliable self-assessment, such as cognitive impairment. METHODS: MS patients and proxies completed the Multiple Sclerosis Impact Scale (MSIS-29) before and after intravenous steroid treatment. Analyses focused on patient-proxy agreement between MSIS-29 change scores. Transition ratings were used to measure the patient's judgement of change and whether this change was reflected in the MSIS-29 change of patients and proxies. Receiver operating characteristic (ROC) analyses were also performed to examine the diagnostic properties of the MSIS-29 when completed by patients and proxies. RESULTS: 42 patients and proxy respondents completed the MSIS-29 at baseline and follow-up. Patient-proxy differences between change scores on the physical and psychological MSIS-29 subscale were quite small, although large variability was found. The direction of mean change was in concordance with the transition ratings of the patients. Results of the ROC analyses of the MSIS-29 were similar when completed by patients (physical scale: AUC = 0.79, 95% CI: 0.65-0.93 and 0.66, 95% CI: 0.48-0.84 for the psychological scale) and proxies (physical scale: 0.80, 95% CI: 0.72-0.96 and 0.71, 95% CI: 0.56-0.87 for the psychological scale) CONCLUSION: Although the results need to be further explored in larger samples, these results do point towards possible use of proxy respondents to assess patient perceived treatment change at the group level.

Longitudinal proxy measurements in multiple sclerosis: patient-proxy agreement on the impact of MS on daily life over a period of two years.

BACKGROUND: The use of self-report measurements in clinical settings is increasing. However, in patients with limitations that interfere with reliable self-assessment such as cognitive impairment or mood disturbances, as may be the case in multiple sclerosis (MS), data collection might be problematic. In these situations, information obtained from proxy respondents (e.g. partners) may replace self-ratings. The aim of this study was to examine the value of proxy ratings at separate points in time and to assess patient-proxy agreement on possible changes in disease impact of MS. METHODS: Fifty-six MS patients and their partners completed the Multiple Sclerosis Impact Scale (MSIS-29) at baseline and follow-up, two years later. Patient-proxy agreement was assessed at both time points by calculating intraclass correlation coefficients (ICCs), exact and global agreement and the mean directional differences between groups. Agreement of change over time was assessed by calculating ICCs between change scores. In parallel, global ratings of both patients and proxy respondents of the extent to which the patient had improved or deteriorated over the past two years were collected to validate possible changes on the MSIS-29. RESULTS: At both time points, agreement on the physical scale was higher than agreement on the psychological scale (ICCs at baseline were 0.81 for the physical scale and 0.72 for the psychological scale; at follow-up, the ICC values were 0.86 and 0.65 respectively). At follow-up, statistically significant mean differences between patients and proxies were noted for the physical scale (-4.8 +/- 12.7, p = 0.006) and the psychological scale (-8.9 +/- 18.8, p = 0.001). Agreement between change scores on the MSIS-29 was fair (ICC < 0.60). Our analyses suggest that the validity of measuring changes over time might be better for proxy respondents compared to patients. CONCLUSION: Proxy respondents could act as a reliable source of information in cross-sectional studies. Moreover, results suggested that agreement on change over time might be better for proxy respondents compared to patients. Although this remarkable finding should be interpreted cautiously because of several limitations of the study, it does plead for further investigation of this important topic.