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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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.
摘要：
背景：以患者为中心的结果表明，所有共济失调患者都需要做好试验准备。Friedreich共济失调评定量表（FARS-ADL）的日常生活活动部分捕获了功能障碍和纵向变化，但仅在Friedreich共济失调中得到验证。
目的：FARS-ADL关于疾病严重程度和对患者有意义的损害的验证，以及它对遗传共济失调变化的敏感性。
方法：分析了298名不同基因型的共济失调患者的FARS-ADL的真实世界登记数据，包括(1)与FARS阶段的互相关，共济失调评估和评级量表(SARA)，患者报告的结果测量（PROM）-共济失调，和欧洲生活质量5维视觉模拟量表（EQ5D-VAS）；（2）对与试验相关的1年中位随访内变化的敏感性，以患者总体变化印象(PGI-C)为基础；(3)因素年龄的一般线性模型，性别,和抑郁症（九项患者健康问卷[PHQ-9]）。
结果：FARS-ADL与总体残疾相关（rhoFARS分期=0.79），临床疾病严重程度（rhoSARA=0.80），和患者报告的损害（rhoPROM-共济失调=0.69，rhoEQ5D-VAS=-0.37），表明全面的结构效度。同样在项目级别，并在基因型(SCA3，RFC1)内验证，FARS-ADL与相应的SARA效应域相关；所有项目与EQ5D-VAS生活质量相关。FARS-ADL对1年间隔的变化敏感，仅在PGI-C恶化的患者中进展。最小的重要变化是1.1。基于稳定PGI-C患者的个体内变异性的点使用FARS-ADL（+0.3分/PHQ-9计数）和EQ5D-VAS捕获抑郁症，但不是FARS阶段或SARA。
结论：FARS-ADL反映了遗传性共济失调的疾病严重程度和对患者有意义的损害，患者对感知变化的试验相关时间尺度的变化具有敏感性。因此，它为即将到来的共济失调试验提供了一个有希望的以患者为中心的结果。©2024作者由WileyPeriodicalsLLC代表国际帕金森症和运动障碍协会出版的运动障碍。
目的：FARS-ADL关于疾病严重程度和对患者有意义的损害的验证，以及它对遗传共济失调变化的敏感性。
方法：分析了298名不同基因型的共济失调患者的FARS-ADL的真实世界登记数据，包括(1)与FARS阶段的互相关，共济失调评估和评级量表(SARA)，患者报告的结果测量（PROM）-共济失调，和欧洲生活质量5维视觉模拟量表（EQ5D-VAS）；（2）对与试验相关的1年中位随访内变化的敏感性，以患者总体变化印象(PGI-C)为基础；(3)因素年龄的一般线性模型，性别,和抑郁症（九项患者健康问卷[PHQ-9]）。
结果：FARS-ADL与总体残疾相关（rhoFARS分期=0.79），临床疾病严重程度（rhoSARA=0.80），和患者报告的损害（rhoPROM-共济失调=0.69，rhoEQ5D-VAS=-0.37），表明全面的结构效度。同样在项目级别，并在基因型(SCA3，RFC1)内验证，FARS-ADL与相应的SARA效应域相关；所有项目与EQ5D-VAS生活质量相关。FARS-ADL对1年间隔的变化敏感，仅在PGI-C恶化的患者中进展。最小的重要变化是1.1。基于稳定PGI-C患者的个体内变异性的点使用FARS-ADL（+0.3分/PHQ-9计数）和EQ5D-VAS捕获抑郁症，但不是FARS阶段或SARA。
结论：FARS-ADL反映了遗传性共济失调的疾病严重程度和对患者有意义的损害，患者对感知变化的试验相关时间尺度的变化具有敏感性。因此，它为即将到来的共济失调试验提供了一个有希望的以患者为中心的结果。©2024作者由WileyPeriodicalsLLC代表国际帕金森症和运动障碍协会出版的运动障碍。
