Sensitivity to change and meaningful difference threshold of the quick motor function test in late onset Pompe disease

Abstract Background The Quick Motor Function Test (QMFT), a 16-item observer-rated scale, assesses motor function in Pompe disease. This study evaluated QMFT’s sensitivity to detect clinical changes and estimated its thresholds for a meaningful difference. Methods Using blinded data from the COMET trial (NCT02782741; registration date: May 25, 2016) in late-onset Pompe disease, we analyzed QMFT’s sensitivity to change from baseline to Week 49. Spearman and polyserial correlations of changes between QMFT and clinical outcome assessments (COAs) were examined, with 95% confidence intervals estimated by bootstrap resampling. Using Kruskal-Wallis analysis, we examined the distribution of QMFT total score changes across three response groups (Improvement, No Change, Worsening) based on other collected and theoretically related COAs as external anchors. Meaningful difference was determined through both anchor-based approaches (using correlations ≥ 0.371) and distribution-based methods, including standard error of measurement (SEM), 0.5 standard deviation (SD), and minimal detectable change (MDC). Results QMFT demonstrated sensitivity to change. Correlations between QMFT and other COAs ranged from |0.14| to |0.39|. Changes in QMFT followed expected patterns among the three response groups. For patients showing any improvement on COAs, anchor-based meaningful difference in QMFT ranged from 4.0 to 8.0 points. Distribution-based estimates yielded similar thresholds for QMFT of 3.9 points (SEM), 5.2 points (0.5SD), and 10.9 points (MDC). Conclusions This study evaluated the QMFT sensitivity to change and defined meaningful difference at which a patient perceives an improvement in their well-being. These data can inform interpretation of QMFT changes in clinical and research setting.