Assessment of the reliability, responsiveness, and meaningfulness of the scale for the assessment and rating of ataxia (SARA) for lysosomal storage disorders.

IF 4.8 2区 医学 Q1 CLINICAL NEUROLOGY
Journal of Neurology Pub Date : 2024-10-01 Epub Date: 2024-09-03 DOI:10.1007/s00415-024-12664-y
Julien Park, Tatiana Bremova-Ertl, Marion Brands, Tomas Foltan, Matthias Gautschi, Paul Gissen, Andreas Hahn, Simon Jones, Laila Arash-Kaps, Miriam Kolnikova, Marc Patterson, Susan Perlman, Uma Ramaswami, Stella Reichmannová, Marianne Rohrbach, Susanne A Schneider, Aasef Shaikh, Siyamini Sivananthan, Matthis Synofzik, Mark Walterfarng, Pierre Wibawa, Kyriakos Martakis, Mario Manto
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引用次数: 0

Abstract

Objective: To evaluate the reliability, responsiveness, and validity of the Scale for the Assessment and Rating of Ataxia (SARA) in patients with lysosomal storage disorders (LSDs) who present with neurological symptoms, and quantify the threshold for a clinically meaningful change.

Methods: We analyzed data from three clinical trial cohorts (IB1001-201, IB1001-202, and IB1001-301) of patients with Niemann-Pick disease type C (NPC) and GM2 Gangliosidoses (Tay-Sachs and Sandhoff disease) comprising 122 patients and 703 visits. Reproducibility was described as re-test reliability between repeat baseline visits or baseline and post-treatment washout visits. Responsiveness was determined in relation to the Investigator's, Caregiver's, and Patient's Clinical Global Impression of Improvement (CGI-I). The CGI-I data was also used to quantify a threshold for a clinically meaningful improvement on the SARA scale. Using a qualitative methods approach, patient/caregiver interviews from the IB1001-301 trial were further used to assess a threshold of meaningful change as well as the breadth of neurological signs and symptoms captured and evaluated by the SARA scale.

Results: The Inter-Class Correlation (ICC) was 0.95 or greater for all three trials, indicating a high internal consistency/reliability. The mean change in SARA between repeat baseline and post-treatment washout visit assessments in all trials was -0.05, SD 1.98, i.e., minimal, indicating no significant differences, learning effects or other systematic biases. For the CGI-I responses and change in SARA scores, Area Under the Curve (AUC) values were 0.82, 0.71, and 0.77 for the Investigator's, Caregiver's, and Patient's CGI-I respectively, indicating strong agreement. Further qualitative analyses of the patient/caregiver interviews demonstrated a 1-point or greater change on SARA to be a clinically meaningful improvement which is directly relevant to the patient's everyday functioning and quality of life. Changes captured by the SARA were also paralleled by improvement in a broad range of neurological signs and symptoms and beyond cerebellar ataxia.

Conclusion: Qualitative and quantitative data demonstrate the reliability and responsiveness of the SARA score as a valid measure of neurological signs and symptoms in LSDs with CNS involvement, such as NPC and GM2 Gangliosidoses. A 1-point change represents a clinically meaningful transition reflecting the gain or loss of complex function.

Abstract Image

评估溶酶体贮积症共济失调评估和评级量表(SARA)的可靠性、响应性和意义。
目的评估共济失调评估和分级量表(SARA)在出现神经症状的溶酶体贮积症(LSD)患者中的可靠性、反应性和有效性,并量化有临床意义的变化的阈值:我们分析了三个临床试验队列(IB1001-201、IB1001-202 和 IB1001-301)的数据,这些临床试验队列由 122 名患者和 703 次就诊组成,分别针对 C 型尼曼-皮克病(NPC)和 GM2 神经节苷脂病(Tay-Sachs 和 Sandhoff 病)患者。再现性是指重复基线访问或基线和治疗后冲洗访问之间的再测可靠性。反应性根据研究者、护理者和患者的临床总体改善印象(CGI-I)来确定。CGI-I 数据还用于量化 SARA 量表上有临床意义的改善的阈值。采用定性方法,进一步利用 IB1001-301 试验中的患者/护理人员访谈来评估有意义变化的阈值以及 SARA 量表所捕捉和评估的神经体征和症状的广度:所有三项试验的类间相关性 (ICC) 均大于或等于 0.95,表明内部一致性/可靠性较高。在所有试验中,重复基线和治疗后冲洗访问评估之间的 SARA 平均变化为 -0.05,SD 1.98,即最小值,表明没有显著差异、学习效应或其他系统性偏差。在 CGI-I 反应和 SARA 评分变化方面,研究人员、护理人员和患者的 CGI-I 曲线下面积(AUC)值分别为 0.82、0.71 和 0.77,表明一致性很高。对患者/护理人员访谈的进一步定性分析显示,SARA 上 1 分或更大的变化是有临床意义的改善,直接关系到患者的日常功能和生活质量。小脑共济失调以外的各种神经系统体征和症状的改善也与 SARA 所捕捉到的变化相吻合:定性和定量数据表明,SARA 评分作为一种有效的神经体征和症状测量方法,对中枢神经系统受累的 LSD(如鼻咽癌和 GM2 神经节苷脂病)具有可靠性和响应性。1分的变化代表了有临床意义的转变,反映了复杂功能的增减。
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来源期刊
Journal of Neurology
Journal of Neurology 医学-临床神经学
CiteScore
10.00
自引率
5.00%
发文量
558
审稿时长
1 months
期刊介绍: The Journal of Neurology is an international peer-reviewed journal which provides a source for publishing original communications and reviews on clinical neurology covering the whole field. In addition, Letters to the Editors serve as a forum for clinical cases and the exchange of ideas which highlight important new findings. A section on Neurological progress serves to summarise the major findings in certain fields of neurology. Commentaries on new developments in clinical neuroscience, which may be commissioned or submitted, are published as editorials. Every neurologist interested in the current diagnosis and treatment of neurological disorders needs access to the information contained in this valuable journal.
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