Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jun;39(6):965-974.
doi: 10.1002/mds.29788. Epub 2024 Mar 20.

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

Andreas Traschütz  1   2 , Zofia Fleszar  2   3 , Holger Hengel  2   3 , Thomas Klockgether  4   5 , Friedrich Erdlenbruch  6 , Björn H Falkenburger  7   8 , Thomas Klopstock  9   10   11 , Özgür Öztop-Çakmak  12 , José Luiz Pedroso  13 , Filippo M Santorelli  14 , Ludger Schöls  2   3 ; RFC1 Study Group, PREPARE Consortium; Matthis Synofzik  1   2
Affiliations

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

Andreas Traschütz et al. Mov Disord. 2024 Jun.

Abstract

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.

Keywords: activities of daily living; ataxia; clinical outcome assessment; trial readiness.

PubMed Disclaimer

References

    1. Klockgether T, Ashizawa T, Brais B, et al. Paving the way toward meaningful trials in ataxias: an ataxia global initiative perspective. Mov Disord 2022;37(6):1125–1130.
    1. Patient‐Focused Drug Development. Selecting, Developing, or Modifying Fit‐for‐Purpose Clinical Outcome Assessments. Food and Drug Administration: U.S; 2022.
    1. Biohaven Provides Update on Phase 3 Clinical Trial Evaluating Troriluzole for Spinocerebellar Ataxia (SCA).
    1. Schmitz‐Hübsch T, du Montcel ST, Baliko L, et al. Scale for the assessment and rating of ataxia: development of a new clinical scale. Neurology 2006;66(11):1717–1720.
    1. Howard JF, Utsugisawa K, Benatar M, et al. Safety and efficacy of eculizumab in anti‐acetylcholine receptor antibody‐positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double‐blind, placebo‐controlled, multicentre study. The Lancet Neurology 2017;16(12):976–986.

LinkOut - more resources