Responsiveness and Minimal Clinically Important Difference of the Motor Function Measure in collagen VI-related dystrophies (COL6-RD) and laminin alpha2-related muscular dystrophy (LAMA2-RD).

Abstract Objective To investigate the responsiveness of the Motor Function Measure (MFM) and determine the Minimal Clinically Important Difference (MCID) in individuals with two common types of congenital muscular dystrophy (CMD). Design Observational, prospective, single center, cohort study. Setting National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NIH). Participants 23 individuals with COL6-RD and 21 individuals with LAMA2-RD enrolled in a 4-year longitudinal natural history study. Interventions Not applicable. Main Outcome Measure Responsiveness of the MFM-32 and the Rasch-scaled MFM-25 and the MCID of the MFM-32 determined from a patient-reported anchor with 2 different methods: within-patient and between-patient. Results Original MFM-32 and Rasch-scaled MFM-25 performed similarly overall in both the COL6-RD and LAMA2-RD populations, with all subscores (D1 standing and transfers, D2 axial and proximal, D3 distal) showing a significant decrease over time, except MFM D3 for LAMA2-RD. MFM D1 subscore was the most sensitive to change for ambulant individuals, whereas MFM D2 subscore was the most sensitive to change for non-ambulant individuals. The MCID for MFM-32 total score was calculated to be 2.5 and 3.9 percentage points according to 2 different methods. Conclusion The MFM showed strong responsiveness in individuals with LAMA2-RD and COL6-RD. Because a floor effect was identified more prominently with the Rasch-Scaled MFM-25, the use of the original MFM-32 as a quantitative variable with the assumption of scale linearity appears to be a good compromise. When designing clinical trials in congenital muscular dystrophies, the use of MCID for MFM should be considered to determine if a given intervention effects show not only a statistically significant change but also a clinically meaningful change.