Denniston Alastair K, Holland Gary N, Kidess Andrej, Nussenblatt Robert B, Okada Annabelle A, Rosenbaum James T, Dick Andrew D
Institute of Translational Medicine, Birmingham Health Partners, University of Birmingham, Birmingham, UK.
Department of Ophthalmology, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
Orphanet J Rare Dis. 2015 Aug 19;10:97. doi: 10.1186/s13023-015-0318-6.
BACKGROUND: Uveitis describes a heterogeneous group of conditions characterized by intraocular inflammation. Since most of the sight-threatening forms of uveitis are individually rare, there has been an increasing tendency for clinical trials to group distinct uveitis syndromes together despite clear variations in phenotype which may reflect real aetiological and pathogenetic differences. Furthermore this grouping of distinct syndromes, and the range of manifestations within each uveitis syndrome, leads to a wide range of possible outcome measures. In this study we wished to review the degree of consensus or otherwise in the choice of primary outcome measures for registered clinical trials related to uveitis. METHODS: Systematic review of data provided in clinical trial registries describing clinical trials dealing with medical treatment of intermediate, posterior, or panuveitis through 01 October 2013. We reviewed 15 on-line clinical trial registries approved by the International Committee of Medical Journal Editors. We identified all that met the following inclusion criteria: prospective, interventional design; target populations with intermediate, posterior or panuveitis; and one or more pre-specified outcome measures that were related to uveitis. Primary outcome measures were classified in terms of type (efficacy or safety or both; single, composite, or multiple); dimension (disease activity, disease damage, measured or patient-reported visual function); and domain (the specific study variable being measured). RESULTS: Of 195 registered uveitis studies, we identified 104 clinical trials that met inclusion criteria. There were 14 different domains used as primary outcome measures. Among clinical trials that utilized primary outcome measures of treatment efficacy (n = 94), 70 (74 %) used a measure of disease activity (vitreous haze in 40/70 [57 %]; macular oedema in 19/70 [27 %]) and 49 (70 %) used a measure of visual function (visual acuity in all cases). Multiple primary outcome measures were used in 23 (22 %) of 104 clinical trials. With regard to quality, in 12 (12 %) of 104 clinical trials, outcome measures were poorly defined. No clinical trial utilized a patient-reported study variable as primary outcome measure. CONCLUSIONS: This systematic review highlights the heterogeneity of outcome measures used in recent clinical trials for intermediate, posterior, and panuveitis. Current designs prioritize clinician-observed measures of disease activity and measurement of visual function as outcome measures. This apparent lack of consensus regarding outcome measures for the study of uveitis is a concern, as it prevents comparison of studies and meta-analyses, and weakens the evidence available to stake-holders, from patients to clinicians to regulators, regarding the efficacy and value of a given treatment.
背景:葡萄膜炎描述了一组以眼内炎症为特征的异质性病症。由于大多数威胁视力的葡萄膜炎形式个体上较为罕见,尽管不同葡萄膜炎综合征在表型上存在明显差异,这些差异可能反映真正的病因和发病机制差异,但临床试验越来越倾向于将不同的葡萄膜炎综合征归为一组。此外,这种不同综合征的分组以及每个葡萄膜炎综合征内的表现范围,导致了广泛的可能结局指标。在本研究中,我们希望回顾已注册的与葡萄膜炎相关的临床试验中主要结局指标选择的共识程度或其他情况。 方法:对临床试验注册机构提供的数据进行系统回顾,这些数据描述了截至2013年10月1日针对中间部、后部或全葡萄膜炎药物治疗的临床试验。我们回顾了由国际医学期刊编辑委员会批准的15个在线临床试验注册机构。我们确定了所有符合以下纳入标准的试验:前瞻性、干预性设计;中间部、后部或全葡萄膜炎的目标人群;以及一个或多个与葡萄膜炎相关的预先指定的结局指标。主要结局指标根据类型(疗效或安全性或两者兼具;单一、复合或多个)、维度(疾病活动度、疾病损害、测量的或患者报告的视觉功能)和领域(所测量的具体研究变量)进行分类。 结果:在195项已注册的葡萄膜炎研究中,我们确定了104项符合纳入标准的临床试验。有14个不同的领域被用作主要结局指标。在使用治疗疗效作为主要结局指标的临床试验中(n = 94),70项(74%)使用了疾病活动度指标(40/70 [57%]为玻璃体混浊;19/70 [27%]为黄斑水肿),49项(70%)使用了视觉功能指标(所有病例均为视力)。104项临床试验中有23项(22%)使用了多个主要结局指标。在质量方面,104项临床试验中有12项(12%)结局指标定义不明确。没有临床试验将患者报告的研究变量用作主要结局指标。 结论:这项系统回顾突出了近期针对中间部、后部和全葡萄膜炎的临床试验中使用的结局指标的异质性。当前的设计将临床医生观察到的疾病活动度指标和视觉功能测量作为优先的结局指标。对于葡萄膜炎研究的结局指标明显缺乏共识令人担忧,因为这妨碍了研究之间的比较和荟萃分析,并削弱了从患者到临床医生再到监管机构等利益相关者可获得的关于特定治疗的疗效和价值的证据。
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