OBJECTIVES: This study aims to critically assess the effectiveness of generic Quality of Life (QoL) questionnaires, particularly the EQ-5D, in capturing the Health-Related Quality of Life (HRQoL) values for Spinal Muscular Atrophy (SMA) and Duchenne Muscular Dystrophy (DMD). It seeks to quantify the extent to which these instruments reflect the individual patient-perceived health-related utility values associated with treatments.

METHODS: A literature review identified key dimensions and themes relevant to SMA and DMD. The content validity of four prevalent QoL instruments — EQ-5D, SF-36, PROMIS-29, and PedsQL 4.0 GCS — was systematically evaluated against these themes. Additionally, expert interviews were conducted to enrich the understanding of the applicability of generic questionnaires in rare diseases and to explore alternative HRQoL measurement methods.

RESULTS: Five dimensions were identified: physical, social, physiological, well-being and the “other”, which contained accessibility/wheelchair use, healthcare service provision, treatment related effects. EQ-5D appeared to be insufficient in covering relevant themes for SMA and DMD, with only 35% of the psychological dimensions, 40% of the physical dimensions, and none of the social dimensions adequately addressed. SF-36 and PROMIS-29 provided more extensive coverage, yet still lacked critical aspects on the “other” domain. PedsQL modules measured HRQoL most accurately, but not fully. The experts recommended disease-specific measures or enhancements to existing tools, suggesting Bolt-ons or Multi-Criteria Decision Analysis to improve the sensitivity of HRQoL assessments in DMD and SMA.

CONCLUSIONS: This analysis indicates that generic QoL questionnaires, including EQ-5D, are insufficient for capturing the complete health-related utility values for SMA and DMD. These findings advocate for the enhancing dimensions for the EQ-5D (Bolt-ons) or using disease-specific measures as additional measurement instruments to the EQ-5D.