Psychometric Validation of the Modified-functional Scale for the Assessment and Rating of Ataxia (P7-3.018)

Objective: Evaluate the psychometric and clinimetric properties of the modified-functional Scale for the Assessment and Rating of Ataxia (f-SARA). Background: International experts developed the SARA to provide semi-quantitative scoring of disorders of motor control in cerebellar ataxia, notably spinocerebellar ataxia (SCA). Accounting for feedback from FDA, a subset of items were selected (gait, stance, sitting, speech) and response options collapsed to a uniform 5-point scale to create f-SARA, a putatively clinically meaningful measure of disease progression. Design/Methods: Two data sources were examined: SCA subjects (ranging in disease severity) enrolled in the PROM-Ataxia validation study (MGH-cohort, cross-sectional) and SCA subjects enrolled in BHV4157-206, 48-week study (NCT03701399, longitudinal). Psychometric properties evaluated were data acceptability (ceiling/floor effects), internal consistency (using Cronbach’s alpha) and test-retest reliability, convergent/divergent validity, and responsiveness. Intra-individual meaningful changes were examined using distribution-based (0.5-SD and SEM) and anchor-based methods (anchor: CGI-I). Results: In subjects enrolled in the MGH-cohort (N=33), ceiling effects were absent while floor effects were observed. Excellent internal consistency was demonstrated (α total =0.90; α items-removed = 0.86–0.90) and item-to-total correlations were strong (r=0.82–0.91, per item). Convergent and divergent validity were supported with stronger correlations observed between the f-SARA and scales of similar construct (p<0.001) (e.g., FARS-FUNC (r=0.92), BARS (r=0.88), PROM-ADL (r=0.83), and FARS-ADL (r=0.69)), while weaker correlations were observed amongst measures of differing constructs. Mean scores (item and total scores) increased with disease severity (p<0.001). Leveraging the BHV4157-206 cohort, high test-retest reliability was demonstrated with intra-class correlation coefficients (ICCs) of 0.91 (total) and 0.73–0.92 (items). A 1-point threshold for meaningful change is supported with 0.5-SD=0.89, SEM=1.19, and mean changes from baseline for patients classified as “improved”, “no change” or “deteriorated” on CGI-I were −0.68, 0.02 and 0.58, respectively. Conclusions: We show that f-SARA has psychometric validity and can detect meaningful change over a 1-year time-period, with a 1-point intra-individual threshold supported. Disclosure: Dr. Potashman has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Evan Popoff has nothing to disclose. Lauren Powell has nothing to disclose. Melissa Beiner has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Melissa Beiner has stock in Biohaven Pharmaceuticals. Miss Mackenzie has received personal compensation for serving as an employee of Biohaven. Vladimir Coric has received personal compensation for serving as an employee of Biohaven. Vladimir Coric has received personal compensation in the range of $1,000,000+ for serving as an officer or member of the Board of Directors for Bioahven. Vladimir Coric has stock in Biohaven. Vladimir Coric has received intellectual property interests from a discovery or technology relating to health care. Dr. Schmahmann has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biohaven. The institution of Dr. Schmahmann has received research support from National Ataxia Foundation. The institution of Dr. Schmahmann has received research support from Biohaven. Dr. Schmahmann has received intellectual property interests from a discovery or technology relating to health care. Dr. Schmahmann has received publishing royalties from a publication relating to health care. Dr. Schmahmann has received publishing royalties from a publication relating to health care. Dr. Schmahmann has received publishing royalties from a publication relating to health care. Gilbert J. L'Italien has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Gilbert J. L'Italien has received stock or an ownership interest from biohaven pharmaceuticals.