A comparison of the measurement properties of the PROMIS Fatigue (MS) 8a against legacy fatigue questionnaires.

BACKGROUND:Amidst the growing number of patient-reported outcome (PRO) measures of fatigue being used in multiple sclerosis (MS) clinical trials and clinics, evidence-based consensus on the most appropriate and generalizable measures across different settings would be beneficial for clinical research and patient care. The objective of this research was to compare the validity and responsiveness of scores from the PROMIS Fatigue (MS) 8a with those of the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS), across US and UK MS populations. METHODS:Two observational studies were performed in MS populations as part of a PRO measure development project, including a cross-sectional study in two tertiary US MS centers (n = 340) and a 96-week longitudinal study in the UK MS Register cohort (n = 352). In post-hoc analyses, we examined  relative validity, based on ability to discriminate across patient groups with different fatigue levels or functional status at baseline (i.e., ANOVA-F PROX ÷ ANOVA-F PROMIS (MS) 8a), and relative responsiveness, based on baseline-to-Week-52 score change (effect sizes) across fatigue or functional status response groups . RESULTS:Mean ± standard deviation (SD) age was 44.6 ± 11.3/50.0 ± 9.7; and 72.9%/77.3% were female (US/UK samples). The mean PROMIS Fatigue (MS) 8a T-score ± SD at baseline was 57.7 ± 10.5/58.9 ± 9.3 (US/UK samples). Compared with the PROMIS Fatigue (MS) 8a, relative validity (anchor: Global Health Score [GHS] fatigue global question) was 85% for MFIS symptom score, 48% for MFIS total score, and 44% for the FSS. Relative to the FSS, PROMIS Fatigue (MS) 8a scores were more sensitive to worsening (effect size = -0.43 versus -0.18) as well as improvement (effect size = 0.5 versus 0.2) in fatigue (≥1-point increase/decrease in GHS fatigue global question) over 52 weeks of follow-up. A similar pattern of score changes was observed based on a second anchor. CONCLUSION:The PROMIS Fatigue (MS) 8a scores showed higher responsiveness to fatigue changes than those of the FSS. The PROMIS measure also had higher precision in differentiating levels of fatigue compared to the FSS, the MFIS physical, and MFIS total scores. These differences have practical implications for the application of these questionnaires in both clinical practice and research settings (e.g., sample size estimation in clinical trials).