Development of patient-reported outcome for spinal and bulbar muscular atrophy

Objectives: To develop and validate a disease-specific patient-reported outcome (PRO) measure for spinal and bulbar muscular atrophy (SBMA). Methods: A three-stage sequential design was adopted. Items were generated through qualitative interviews with patients with SBMA and expert review, refined using quantitative analyses, and evaluated for reliability and validity in independent cohorts from Japan and the United States. Results: Interviews with 12 patients generated 234 candidate items, which were refined into a final 31-item SBMAPRO comprising five domains based on an online survey of 106 patients. Internal consistency across domains ranged from Cronbach's alpha values of 0.651 to 0.901. In the Japanese cohort, test-retest reliability yielded intraclass correlation coefficients of 0.941 for physical function, 0.877 for mental health, and 0.858 for social function. Construct validity was examined through correlations with disease-specific functional measurements and the 36-Item Short Form Survey (SF-36). The SBMAPRO correlated with the SBMA Functional Rating Scale (r = -0.826, p <0.001) and with the SF-36 mental health (r = -0.693, p <0.001) and social functioning (r = -0.617, p <0.001) domains. In subscale analyses, the SBMAPRO social domain was associated with trunk-lower limb-related functional impairment (r = -0.587, p < 0.001). Similar patterns were observed in the American cohort. Conclusion: The SBMAPRO demonstrated reliability and validity in Japanese and American cohorts. Associations between mental and social domains and trunk-lower limb dysfunction suggest that mobility impairment may contribute to psychological burden and restricted social participation in SBMA, indicating that this disease-specific PRO may complement clinician-rated measures.