OBJECTIVES

Metachromatic leukodystrophy (MLD) is an ultra-rare, neurodegenerative disease which leads to motor and cognitive decline, and premature death. Hitherto, its impact on health-related quality of life (HRQL) of infants and juveniles has not been quantified. The aim of this study was to elicit societal utility values for infantile and juvenile MLD to support the economic evaluation of therapies.

METHODS

Health states were segregated by age of disease onset: infant (<30 months) and juvenile (30 months to 16 years). Infant health states were defined by the Gross Motor Function Classification (GMFC-MLD); whilst juvenile health states were defined by GMFC-MLD and by Development Quotient (DQ) scores for three cognitive functioning levels from normal/mild, moderate, and severe. Health state descriptions were informed by literature review and interviews with clinical experts (N=6) - who also validated the draft states in cognitive debriefing interviews. The finalised health states were valued by UK general public (n=101) who completed a visual analogue scale (VAS) and time trade-off (TTO) assessment with the lead time method.

RESULTS

Amongst infantile states, the mean TTO values ranged from 0.71 (GMFC-MLD1) to -0.47 (GMFC-MLD6). Each decline in GMFC-MLD was associated with worsening TTO and VAS scores. The juvenile states had considerably lower utility values than infantile states and also declined with worsening cognitive status. In the normal cognitive group, the mean utility values ranged from 0.90 (GMFC-MLD1) to -0.07 (GMFC-MLD4). In the moderate group, the mean scores ranged from 0.85 (GMFC-MLD0) to -0.62 (GMFC-MLD6). In the severe group, mean scores ranged from 0.37 (GMFC-MLD0) to -0.70 (GMFC-MLD5).

CONCLUSIONS

This study has generated de novo utility estimates for infantile and juvenile MLD health states, and is one of the first studies to measure the cognitive dimension of an ultra-rare disease. The utility values confirm that the preferences of the general public recognise the severity of MLD.