Department of Biostatistics and Medical Informatics and Pitié-Salpêtrière Charles-Foix Clinical Research Unit, AP-HP, Paris, France.
Mov Disord. 2011 Feb 15;26(3):534-8. doi: 10.1002/mds.23531. Epub 2011 Feb 1.
Responsive ataxia rating scales are essential for determining outcome measures in clinical trials.
We evaluated the responsiveness over time of the composite cerebellar functional severity score, a quantitative score measuring cerebellar ataxia in 133 patients with autosomal dominant cerebellar ataxias (ADCA), which were prospectively evaluated at inclusion and after one-year of follow-up. A more responsive tool was developed, the Cerebellar Functional Severity score writing, incorporating the writing test at dominant hand to the Cerebellar Functional Severity score.
Within the one-year follow-up period, the Cerebellar Functional Severity score and its writing version increased significantly and the Scale for the Assessment and Rating of Ataxia decreased significantly reflecting increased severity of the cerebellar symptoms. The Cerebellar Functional Severity score writing responsiveness was best in genotypes SCA1, 2, and 3 compared with the other genotypes (effect size = 0.196, standardized response mean (SRM) = 0.624 versus effect size = -0.051, SRM = -0.150). The Cerebellar Functional Severity score writing used as an outcome measure would require only 163 SCA1, 2, or 3 patients per group in a two-arm interventional trial for a 50% reduction in progression and 80% of power.
Our study demonstrates that the Cerebellar Functional Severity score and Cerebellar Functional Severity score writing are responsive quantitative scores for evaluating sensitivity to change in ADCA patients and can be used as outcome measures in clinical trials, especially when targeting genotypes SCA1, 2 and 3.
响应性共济失调评分量表对于确定临床试验中的结果测量至关重要。
我们评估了复合小脑功能严重程度评分的随时间变化的响应性，这是一种定量评分，用于测量 133 例常染色体显性小脑共济失调（ADCA）患者的小脑共济失调，这些患者在纳入时和随访一年后进行了前瞻性评估。开发了一种更敏感的工具，即小脑功能严重程度书写评分，将主导手的书写测试纳入小脑功能严重程度评分。
在一年的随访期间，小脑功能严重程度评分及其书写版本显著增加，而共济失调评估和评分量表显著降低，反映出小脑症状的严重程度增加。与其他基因型相比，小脑功能严重程度书写评分在 SCA1、2 和 3 基因型中的反应性最佳（效应大小=0.196，标准化反应均值（SRM）=0.624 与效应大小=-0.051，SRM=-0.150）。小脑功能严重程度书写评分作为一种结局测量指标，在一项两臂干预试验中，每组只需 163 例 SCA1、2 或 3 患者，即可达到 50%的进展减少和 80%的效力。
我们的研究表明，小脑功能严重程度评分和小脑功能严重程度书写评分是评估 ADCA 患者对变化敏感性的敏感定量评分，可用于临床试验中的结局测量指标，特别是当针对 SCA1、2 和 3 基因型时。
