Abstract
BACKGROUND AND OBJECTIVES: Understanding the reliability of outcomes used in clinical care and trials is important to delineate intervention-induced change from random variability. Reliability, sensitivity, and clinical meaningfulness of change are all key aspects of choosing the most appropriate outcome measure for a clinical trial. Common outcome measures to monitor progression and treatment effect in Duchenne muscular dystrophy (DMD) include measures of strength (myometry) and motor function tests: stand from supine velocity (STANDV), North Star Ambulatory Assessment (NSAA), 6-minute walk distance (6MWD), 10-m run/walk (RWV), and 4-stair climb velocity (CLIMBV). Our objective was to present test-retest reliability of common outcome measures using pretreatment measurements and to provide insights into missing measurements. METHODS: Data were used on outcome measures in steroid-naïve, 4 to <7 years participants with DMD in 2 multisite, multicountry vamorolone trials (VBP15-002 [n = 48 participants] and VBP15-004 [n = 121 participants]). Bland-Altman analysis, the coefficient of variation, and the intraclass correlation coefficient (ICC) were used. RESULTS: Based on the ICC, NSAA, RWV, and CLIMBV have good reliability, whereas the 6MWD and STANDV have moderate reliability. Two different techniques were used for myometry in VBP15-002 (CINRG Quantitative Measurement System [CQMS]) and VBP15-004 (MicroFET2 handheld digital muscle dynamometer [HHD]). Reliability of myometry ranged from poor to moderate, and CQMS did not show improved reliability over HHD. The 6MWD and myometry showed the highest rates of missingness. Because of similar age ranges and harmonized outcomes, our findings were compared with the FOR-DMD cohort. Myometry and CLIMBV were not in FOR-DMD; reliability findings were concordant for the 4 outcomes in common. For most outcomes, we found reduced reliability compared with previous studies in older age groups. DISCUSSION: Reliable outcome measures, appropriate for the age of patients, are key to improving power in clinical trials, leading to fewer participants needed and reducing patient and site burden. We found NSAA, RWV, and CLIMBV to be the most reliable. This should be considered in the context of sensitivity to drug effect, and clinical meaningfulness of changes observed: all 5 motor outcomes were sensitive to drug effect of vamorolone and prednisone, whereas myometry was not.