NIHR Moorfields Eye Hospital Biomedical Research Centre, London, UK.
NIHR Great Ormond Street Hospital Biomedical Research Centre, London, UK.
Orphanet J Rare Dis. 2019 Jun 6;14(1):125. doi: 10.1186/s13023-019-1108-3.
Childhood uveitis is a collection of chronic rare inflammatory eye disorders which result in visual loss in at least one eye of one fifth of affected children. Despite the introduction of novel systemic immunochemotherapies, it remains a blinding disease. We have undertaken a systematic review of outcome measures used in interventional trials of children with, or at risk of uveitis, in order to investigate metric quality and heterogeneity, as possible barriers to the translation of clinical research into improved outcomes.
Systematic review of trials registered within databases approved by the International Committee of Medical Journal Editors (ICMJE). Eligible trials for were those which involved participants aged under 18 years with or at risk of non-infectious uveitis. Data on date of study commencement, uveitis site, inclusion age criteria, and outcome measure characteristics including type, dimension and quality were extracted independently by two authors. Quality was determined using the reproducibility, validity and age-appropriateness of the metric.
Of 917 identified trials, 57 were eligible for inclusion. Twenty different domains across five dimensions were used as primary outcome measures. The structure most commonly used was multiple separate outcome measures. In a quarter of studies, outcomes were assessed less than 3 months following the intervention. Disease activity was the most commonly assessed dimension, with only 30 studies (60%) using reproducible methodologies to assess activity. Only 2/12 (18%) studies on intermediate or posterior uveitis used reproducible activity grading schemes. Of 18 studies involving children aged under 6 years old which used outcome measures related to visual function, only 8/18 (44%) described the use of age-appropriate acuity assessment measures. None of the studies used a vision related quality of life metrics which had been validated for use in childhood.
This review of outcome measures in childhood uveitis interventional trials has identified under-utilisation of reproducible or child appropriate measures, and considerable heterogeneity in metric type, and structure. Clinicians and researchers interested in improving outcomes for affected children must identify a patient and family centred core outcome set, and work to validate both objective and patient (or proxy) reported disease age appropriate outcome measures.
儿童葡萄膜炎是一组慢性罕见的眼部炎症性疾病，其中至少五分之一的受累儿童会有一只或多只眼睛失明。尽管引入了新型全身免疫化学疗法，但它仍然是一种致盲性疾病。我们对儿童葡萄膜炎或有葡萄膜炎风险的干预性试验中使用的结局指标进行了系统回顾，以调查可能对临床研究转化为改善结局造成障碍的指标质量和异质性。
对国际医学期刊编辑委员会（ICMJE）批准的数据库中注册的试验进行系统回顾。纳入的试验必须是年龄在 18 岁以下且患有或有患非感染性葡萄膜炎风险的参与者。两名作者独立提取研究开始日期、葡萄膜炎部位、纳入年龄标准以及结局指标特征（包括类型、维度和质量）的数据。使用指标的可重复性、有效性和年龄适宜性来确定质量。
在确定的 917 项试验中，有 57 项符合纳入标准。5 个维度的 20 个不同领域被用作主要结局指标。最常用的结构是多个单独的结局指标。在四分之一的研究中，在干预后不到 3 个月评估结局。疾病活动是最常评估的维度，只有 30 项研究（60%）使用可重复的方法评估活动。仅有 2/12（18%）关于中后部葡萄膜炎的研究使用了可重复的活动分级方案。在 18 项涉及年龄在 6 岁以下的儿童的、与视觉功能相关的结局指标的研究中，只有 8/18（44%）描述了使用年龄适宜的视力评估方法。没有一项研究使用经过验证可用于儿童的与视觉相关的生活质量指标。
对儿童葡萄膜炎干预性试验结局指标的回顾发现，可重复性或适合儿童的指标使用不足，且指标类型和结构存在很大的异质性。对改善受影响儿童结局感兴趣的临床医生和研究人员必须确定以患者和家庭为中心的核心结局集，并努力验证客观和患者（或代理）报告的适合疾病年龄的结局指标。
