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.

中文翻译：

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Rett综合征的临床试验指标评估：Rett综合征行为问卷的关键分析。

背景技术Rett综合征是一种神经发育障碍，具有通过新型靶向疗法改善的潜力。可靠的结果指标对于治疗的发展至关重要。我们研究了瑞特综合症行为问卷的优缺点，这是临床试验的结果指标。方法通过三个队列，在线调查，基于临床的研究以及临床试验的筛选期，与其他临床量表一起进行了瑞特综合症行为问卷调查。在三个时间点从患有Rett综合征和相关疾病的个体中收集数据，间隔时间最少为一周，最长为两个月。我们假设对于临床试验用途，访视之间应几乎没有变化。分布统计，内部一致性，类内相关系数，百分比同意，并检查了科恩的kappa。结果在149名典型的Rett综合征患者中，Rett综合征行为问卷完成了377次。中位数总分是33，范围是3到73。在最初的Rett综合征行为问卷研究中测试的51个项目中，有24个表现出地板效应或天花板效应。弗里德曼（Friedman）的方差分析显示访问之间存在显着差异（P = 0.024），使用布兰德-奥特曼（Bland-Altman）图进行的图形分析表明，系统的正偏差具有95％的置信区间，包括高达12.9点至重新测试的15.7点。在访问2时通过kappa测得的中位数一致性为0.53，在访问3时为0.49（重新测试）。