FARS‐ADL across Ataxias: Construct Validity, Sensitivity to Change, and Minimal Important Change

• Published in: Movement disorders 2024-06, Vol.39 (6), p.965-974
• Main Authors: Traschütz, Andreas, Fleszar, Zofia, Hengel, Holger, Klockgether, Thomas, Erdlenbruch, Friedrich, Falkenburger, Björn H., Klopstock, Thomas, Öztop‐Çakmak, Özgür, Pedroso, José Luiz, Santorelli, Filippo M., Schöls, Ludger, Synofzik, Matthis
• Format: Article
• Language: English
• Subjects: Activities of Daily Living; Adult; Aged; Ataxia; Ataxia - diagnosis; Ataxia - physiopathology; clinical outcome assessment; Clinical trials; Female; Friedreich Ataxia - diagnosis; Friedreich Ataxia - genetics; Friedreich Ataxia - physiopathology; Friedreich's ataxia; Genotypes; Humans; Male; Middle Aged; Minimal Clinically Important Difference; Movement disorders; Patient Reported Outcome Measures; Patients; Quality of Life; Registries; Reproducibility of Results; Severity of Illness Index; trial readiness; Validation studies; Young Adult
• ISSN: 0885-3185; 1531-8257; 1531-8257
• DOI: 10.1002/mds.29788

Background Patient‐focused outcomes present a central need for trial‐readiness across all ataxias. The Activities of Daily Living part of the Friedreich Ataxia Rating Scale (FARS‐ADL) captures functional impairment and longitudinal change but is only validated in Friedreich Ataxia. Objective Validation of FARS‐ADL regarding disease severity and patient‐meaningful impairment, and its sensitivity to change across genetic ataxias. Methods Real‐world registry data of FARS‐ADL in 298 ataxia patients across genotypes were analyzed, including (1) cross‐correlation with FARS‐stage, Scale for the Assessment and Rating of Ataxia (SARA), Patient‐Reported Outcome Measure (PROM)‐ataxia, and European Quality of Life 5 Dimensions visual analogue scale (EQ5D‐VAS); (2) sensitivity to change within a trial‐relevant 1‐year median follow‐up, anchored in Patient Global Impression of Change (PGI‐C); and (3) general linear modeling of factors age, sex, and depression (nine‐item Patient Health Questionnaire [PHQ‐9]). Results FARS‐ADL correlated with overall disability (rhoFARS‐stage = 0.79), clinical disease severity (rhoSARA = 0.80), and patient‐reported impairment (rhoPROM‐ataxia = 0.69, rhoEQ5D‐VAS = –0.37), indicating comprehensive construct validity. Also at item level, and validated within genotype (SCA3, RFC1), FARS‐ADL correlated with the corresponding SARA effector domains; and all items correlated to EQ5D‐VAS quality of life. FARS‐ADL was sensitive to change at a 1‐year interval, progressing only in patients with worsening PGI‐C. Minimal important change was 1.1. points based on intraindividual variability in patients with stable PGI‐C. Depression was captured using FARS‐ADL (+0.3 points/PHQ‐9 count) and EQ5D‐VAS, but not FARS‐stage or SARA. Conclusion FARS‐ADL reflects both disease severity and patient‐meaningful impairment across genetic ataxias, with sensitivity to change in trial‐relevant timescales in patients perceiving change. It thus presents a promising patient‐focused outcome for upcoming ataxia trials. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.