Responsiveness of the Scale for the Assessment and Rating of Ataxia and Natural History in 884 Recessive and Early Onset Ataxia Patients

Objective The Scale for the Assessment and Rating of Ataxia (SARA) is the most widely applied clinical outcome assessment (COA) for genetic ataxias, but presents metrological and regulatory challenges. To facilitate trial planning, we characterize its responsiveness (including subitem‐level relations to ataxia severity and patient‐focused outcomes) across a large number of ataxias, and provide first natural history data for several of them. Methods Subitem‐level correlation and distribution‐based analysis of 1,637 SARA assessments in 884 patients with autosomal recessive/early onset ataxia (370 with 2–8 longitudinal assessments) were complemented by linear mixed effects modeling to estimate progression and sample sizes. Results Although SARA subitem responsiveness varied between ataxia severities, gait/stance showed a robust granular linear scaling across the broadest range (SARA