Development and testing the psychometric properties of 20 bolt-on items for the EQ-5D-5L across 31 rare diseases

Objective: Our objective was to develop and assess the psychometric properties of relevant bolt-on items for the EQ-5D-5L in patients with rare diseases (RDs). Methods: Nineteen new EQ-5D-5L bolt-ons were developed based on literature review, expert input and qualitative interviews and focus groups with patients, caregivers and representatives of patient associations. A nationwide, cross-sectional, web-based survey in China included patients or caregivers of patients with 31 RDs in China (n=9,190). In each RDs, participants completed the EQ-5D-5L and three out of 20 [one existing and 19 newly-developed] bolt-ons. Ceiling, explanatory power, convergent, divergent and known-group validity were examined. Results: Among the bolt-ons, itching had the lowest ceiling (6.5%), while social relationships had the highest (42.2%). The absolute reduction in the ceiling of the EQ-5D-5L with the addition of any bolt-ons was limited, ranging from 0 (respiratory problems) to 8.3%-points (isolation). Dignity and vitality resulted in the largest increase in explained variance in EQ VAS. The isolation, fertility and visual acuity bolt-ons showed good divergent validity from the EQ-5D-5L items. There was strong convergent validity between SF-12 and conceptually-related bolt-ons (e.g., physical health composite and muscle problems bolt-on). Various bolt-ons improved the known-groups validity in specific patient groups, e.g., Huntington’s disease (oral expressions), scleroderma (dexterity), myasthenia gravis (muscle problems), neuromyelitis optica and multiple sclerosis (fatigue), Marfan syndrome (self-image) and Pompe disease (safety). Conclusion: The EQ-5D-5L shows sufficient validity in most RDs, but incorporating relevant specific bolt-ons could enhance its ability to more comprehensively assess health-related quality of life in these patients.