Measurement Properties of the Friedrich’s Ataxia Rating Scale – Activities of Daily Living in Patients with Spinocerebellar Ataxia

Topic:

Other

Poster Number: M276

Author(s):

Michele Potashman, M.S., PhD, Biohaven, Evan Popoff, MSc, Broadstreet HEOR, Vancouver, BC, CAN, Lauren Powell, MPH, Broadstreet Health Economics & Outcomes Research, Vancouver, BC, Canada, Melissa Beiner, MD, Biohaven Pharmaceuticals, Inc., Ainsley Mackenzie, BS, Biohaven Pharmaceuticals, Inc., New Haven, CT, USA, Vlad Coric, MD, Biohaven Pharmaceuticals, Inc., New Haven, CT, USA, S H Subramony, M.D., Univsersity of Florida, Fixel Center for Neurological Disorders, Jeremy D Schmahmann, MD, Ataxia Center, Laboratory for Neuroanatomy and Cerebellar Neurobiology, Department of Neurology, MGH, Gil L'italien, PhD, Biohaven

Background: The Friedrich’s Ataxia Rating Scale – Activities of Daily Living (FARS-ADL) is a valid and highly utilized measure for assessing the ADL impacts in patients with Friedrich’s Ataxia. While often included in spinocerebellar ataxia (SCA) studies, its measurement properties in SCA populations have not been reported. Herein we examine the psychometric validity of the FARS-ADL in subjects with SCA.

Methods: Two data sources were examined: SCA subjects (ranging in disease severity) enrolled in PROM-Ataxia validation study (MGH-cohort, cross-sectional) and SCA subjects enrolled in BHV4157-206 (NCT03701399, 48-week study). Psychometric properties evaluated were data acceptability (ceiling/floor effects), internal consistency (Cronbach’s alpha), 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: Among subjects enrolled in the MGH-cohort (N=33), ceiling effects were absent while floor effects were observed on all items except walking. Excellent internal consistency was demonstrated (αtotal=0.88; αitems-removed= 0.86-0.87) and item-to-total correlations were acceptable (r=0.55-0.89, per item). Convergent and divergent validity were supported with stronger correlations observed between the FARS-ADL and scales of similar construct (p<0.001) (e.g., Neuro-QOL-upper (r=-0.90), Neuro-QOL-lower (r=-0.81), PROM-ADL (r=0.83), and PROM-PHYS (r=0.82) and FARS-FUNC (r=0.78)), with weaker correlations amongst measures of differing constructs (e.g., PROM-MENTAL [r=0.54, p=0.001]). Mean scores on n=6/9 items and total score increased with disease severity (p=0.001), except swallowing, sitting and bladder items. Using BHV4157-206 (N=217) data, empirical cumulative distribution function curves by CGI-I status showed the 3 curves (“improved”, “no change” or “deteriorated”) as clearly differentiated in the -2 to +3 change range; 50% of patients had FARS-ADL changes of -1, 0 and +1 points, respectively. Distribution-based findings were 0.5-SD=2.43 and SEM=2.19; data triangulation supports 2-3 points range as minimally important change. Conclusions: We show FARS-ADL has psychometric validity in the SCA population and may detect meaningful changes over a 1-year time-period.