The American College of Rheumatology Provisional Composite Response Index for Clinical Trials in Early Diffuse Cutaneous Systemic Sclerosis
The American College of Rheumatology Provisional Composite Response Index for Clinical Trials in Early Diffuse Cutaneous Systemic Sclerosis
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DOI：
10.1002/art.39501
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发表时间：
2016-02-01
影响因子：
13.3
通讯作者：
Furst, Daniel E.
中科院分区：
文献类型：
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作者：
Khanna, Dinesh;Berrocal, Veronica J.;Furst, Daniel E.
Objective.早期弥漫性皮肤系统性硬化症（dcSSc）的特征是皮肤和内脏器官的快速变化。本研究的目的是开发一种用于随机对照试验（RCT）的dcSSc复合反应指数（CRISS）。我们使用dcSSc患者开发了150份具有标准化临床结局要素（核心集项目）的纸质患者资料。40名硬皮病专家对20名患者的个人资料进行了评估，并评估了每名患者在1年内是否有所改善。使用评分者就患者是否改善达成共识的概况（检查的79%的概况），我们拟合logistic回归模型，其中二元结局指的是患者是否改善，核心集项目从基线到随访的变化作为协变量输入。我们在先前完成的RCT中测试了最终指数。在共识会议和审查患者水平数据的测试特征后，31个核心项目中的16个被纳入患者资料。在logistic回归模型中，纳入的核心集项目为改良Rodnan皮肤厚度评分、用力肺活量、患者和医生总体评估以及健康评估问卷残疾指数在1年内的变化，灵敏度为0.982（95%可信区间0.982-0.983），特异度为0.931（95%可信区间0.930-0.932），这5项的模型具有最高的面效度。肾脏或心肺受累显著恶化的受试者被归类为未改善，无论其他核心项目是否改善。在1年的随机对照试验中，使用该指数可以区分甲氨蝶呤和安慰剂的疗效（P=0.02）。我们开发了一种CRISS，适合用作早期dcSSc RCT的结局评估。
Objective. Early diffuse cutaneous systemic sclerosis (dcSSc) is characterized by rapid changes in the skin and internal organs. The objective of this study was to develop a composite response index in dcSSc (CRISS) for use in randomized controlled trials (RCTs).Methods. We developed 150 paper patient profiles with standardized clinical outcome elements (core set items) using patients with dcSSc. Forty scleroderma experts rated 20 patient profiles each and assessed whether each patient had improved or not improved over a period of 1 year. Using the profiles for which raters had reached a consensus on whether the patients were improved versus not improved (79% of the profiles examined), we fit logistic regression models in which the binary outcome referred to whether the patient was improved or not, and the changes in the core set items from baseline to followup were entered as covariates. We tested the final index in a previously completed RCT.Results. Sixteen of 31 core items were included in the patient profiles after a consensus meeting and review of test characteristics of patient-level data. In the logistic regression model in which the included core set items were change over 1 year in the modified Rodnan skin thickness score, the forced vital capacity, the patient and physician global assessments, and the Health Assessment Questionnaire disability index, sensitivity was 0.982 (95% confidence interval 0.982-0.983) and specificity was 0.931 (95% confidence interval 0.930-0.932), and the model with these 5 items had the highest face validity. Subjects with a significant worsening of renal or cardiopulmonary involvement were classified as not improved, regardless of improvements in other core items. With use of the index, the effect of methotrexate could be differentiated from the effect of placebo in a 1-year RCT (P=0.02).Conclusion. We have developed a CRISS that is appropriate for use as an outcome assessment in RCTs of early dcSSc.