Department of Molecular Medicine, Cardiology Unit, University of Pavia, Italy (S.L.).
Coronary Care Unit (S.L.), Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.
Circ Cardiovasc Qual Outcomes. 2021 Feb;14(2):e006581. doi: 10.1161/CIRCOUTCOMES.120.006581. Epub 2021 Feb 4.
Event adjudication by a clinical event committee (CEC) provides a standardized, independent outcome assessment. However, the added value of CEC to investigators reporting remains debated. GLASSY (GLOBAL LEADERS Adjudication Sub-Study) implemented, in a subset of the open-label, investigator-reported (IR) GLOBAL LEADERS trial, an independent adjudication process of reported and unreported potential outcome events (triggers). We describe metrics of GLASSY feasibility and efficiency, diagnostic accuracy of IR events, and their concordance with corresponding CEC-adjudicated events.
We report the proportion of myocardial infarction, bleeding, stroke, and stent thrombosis triggers with sufficient evidence for assessment (feasibility) that were adjudicated as outcome events (efficiency), stratified by source (IR or non-IR). Using CEC-adjudicated events as criterion standard, we describe sensitivity, specificity, positive and negative predictive value, and global diagnostic accuracy of IR events. Using Gwet AC coefficient, we examine the concordance between IR- and corresponding CEC-adjudicated triggers. There was sufficient evidence for assessment for 2592 (98.3%) of 2636 triggers.
Overall, the adjudicated end point-to-trigger ratio was high and similar between IR- (88%) and non-IR-reported (87%) triggers. The global diagnostic accuracy and concordance between IR-reported and CEC-adjudicated outcome events was 0.70 (95% CI, 0.65-0.74) and 0.54 (95% CI, 0.45-0.62), respectively, for myocardial infarction; 0.77 (95% CI, 0.75-0.79) and 0.71 (95% CI, 0.68-0.74) for bleeding; 0.70 (95% CI, 0.62-0.79) and 0.59 (95% CI, 0.43-0.74) for stroke; 0.59 (95% CI, 0.52-0.66) and 0.39 (95% CI, 0.25-0.53) for stent thrombosis. For IR bleedings, the concordance with the CEC on type of events was generally weak.
Implementing CEC adjudication in a pragmatic open-label trial with IR events is feasible and efficient. Our findings of modest global diagnostic accuracy for IR events and generally weak concordance between investigators and CEC support the role for CEC adjudication in such settings. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03231059.
临床事件委员会（CEC）的事件裁定为标准化、独立的结局评估提供了支持。然而，CEC 对研究者报告的附加价值仍存在争议。GLASSY（GLOBAL LEADERS 裁定子研究）在开放标签、研究者报告（IR）GLOBAL LEADERS 试验的一个亚组中实施了潜在结局事件（触发因素）的独立裁定程序，这些触发因素既有报告的，也有未报告的。我们描述了 GLASSY 的可行性和效率指标、IR 事件的诊断准确性及其与相应的 CEC 裁定事件的一致性。
我们报告了心肌梗死、出血、卒中和支架血栓形成触发因素的比例，这些触发因素具有足够的评估证据（可行性），并按来源（IR 或非 IR）分层，这些触发因素被裁定为结局事件（效率）。使用 CEC 裁定的事件作为标准，我们描述了 IR 事件的敏感性、特异性、阳性和阴性预测值以及整体诊断准确性。使用 Gwet AC 系数，我们研究了 IR 和相应的 CEC 裁定触发因素之间的一致性。在 2636 个触发因素中，有 2592 个（98.3%）具有足够的评估证据。
总体而言，IR（88%）和非 IR 报告（87%）触发因素的裁定终点与触发因素之比均较高且相似。IR 报告和 CEC 裁定结局事件的全球诊断准确性和一致性分别为 0.70（95%CI，0.65-0.74）和 0.54（95%CI，0.45-0.62），心肌梗死为 0.77（95%CI，0.75-0.79）和 0.71（95%CI，0.68-0.74），出血为 0.70（95%CI，0.62-0.79）和 0.59（95%CI，0.43-0.74），卒中和支架血栓形成分别为 0.59（95%CI，0.52-0.66）和 0.39（95%CI，0.25-0.53）。对于 IR 出血，CEC 裁定与事件类型的一致性通常较弱。
在具有 IR 事件的实用开放标签试验中实施 CEC 裁定具有可行性和效率。我们发现 IR 事件的整体诊断准确性适中，且研究者与 CEC 之间的一致性通常较弱，这支持 CEC 裁定在这种情况下的作用。注册：网址：https://www.clinicaltrials.gov；唯一标识符：NCT03231059。
