评估用于雷特综合征的临床试验指标：对雷特综合征行为问卷的批判性分析。
Assessment of a Clinical Trial Metric for Rett Syndrome: Critical Analysis of the Rett Syndrome Behavioural Questionnaire.
机构信息
Stony Brook University Medical Center, Stony Brook, New York.
University of Georgia, Athens, Georgia.
出版信息
Pediatr Neurol. 2020 Jun;107:48-56. doi: 10.1016/j.pediatrneurol.2020.01.009. Epub 2020 Feb 4.
BACKGROUND
Rett syndrome is a neurodevelopmental disorder with potential for improvement through novel targeted therapeutics. Reliable outcome measures are critical to the development of treatments. We examined the merits and flaws of the Rett Syndrome Behavioural Questionnaire, an outcome measure for clinical trials.
METHODS
The Rett Syndrome Behavioural Questionnaire was administered alongside other clinical scales in three cohorts, an online survey, a clinic-based study, and the screening period for a clinical trial. Data were collected from individuals with Rett syndrome and related disorders at three time points, separated by a minimum of one week and a maximum of two months. We hypothesized that for clinical trial use, little change should occur among visits. Distribution statistics, internal consistency, intraclass correlation coefficient, percent agreement, and Cohen's kappa were examined.
RESULTS
Among 149 with classic Rett syndrome, the Rett Syndrome Behavioural Questionnaire was completed 377 times. Median total score was 33, ranging from 3 to 73. Of the 51 items tested in the original Rett Syndrome Behavioural Questionnaire study, 24 exhibited either floor or ceiling effects. Friedman's analysis of variance revealed significant difference among visits (P = 0.024), and graphical analysis using Bland-Altman plots demonstrated systematic positive bias with a 95% confidence interval including up to 12.9 points higher to 15.7 points lower at retest. Median agreement measured by kappa was 0.53 for retest at visit 2 and 0.49 for retest at visit 3.
CONCLUSIONS
The Rett Syndrome Behavioural Questionnaire did not achieve acceptable standards as an outcome assessment for clinical trials in Rett syndrome.
背景
Rett 综合征是一种神经发育障碍，通过新型靶向治疗可能会有所改善。可靠的结局评估指标对于治疗方法的开发至关重要。我们研究了 Rett 综合征行为问卷（一种临床试验的结局评估指标）的优缺点。
方法
在三个队列中，即在线调查、基于诊所的研究以及临床试验的筛选期，同时使用 Rett 综合征行为问卷和其他临床量表对患者进行评估。数据收集自至少间隔 1 周且最长不超过 2 个月的三个时间点的 Rett 综合征和相关疾病患者。我们假设，对于临床试验的应用，在不同的就诊时间点变化应很小。分析了分布统计、内部一致性、组内相关系数、百分比一致性和 Cohen's kappa。
结果
在 149 名经典 Rett 综合征患者中，共完成了 377 次 Rett 综合征行为问卷评估。总分中位数为 33，范围为 3 至 73。在原始 Rett 综合征行为问卷研究中测试的 51 个项目中，有 24 个表现出地板或天花板效应。Friedman 方差分析显示就诊时间之间存在显著差异（P=0.024），Bland-Altman 图的图形分析显示存在系统的正偏倚，95%置信区间包括最高 12.9 分的偏高至最低 15.7 分的偏低。以 kapp 值衡量的中位数一致性，在第 2 次就诊的复测时为 0.53，在第 3 次就诊的复测时为 0.49。
结论
Rett 综合征行为问卷未达到 Rett 综合征临床试验结局评估的可接受标准。
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