Department of Neurology, University of California, San Francisco, USA.
Global Medicines Development, AstraZeneca, Gothenburg, Sweden.
Int J Stroke. 2019 Dec;14(9):908-914. doi: 10.1177/1747493019851282. Epub 2019 May 15.
Adjudication of endpoints is a standard procedure in cardiovascular clinical trials. However, several studies indicate that the benefit of adjudication in estimating treatment effect may be limited.
This post hoc analysis of SOCRATES (NCT01994720) compared the treatment effects and investigated the agreement of clinical event assessment by site investigators and independent adjudicators.
SOCRATES compared ticagrelor and aspirin in 13,199 patients with acute minor stroke or high-risk transient ischemic attack. The primary endpoint was stroke, myocardial infarction, or death. Stroke was the major component of the primary endpoint and a secondary endpoint. The endpoints were adjudicated by a blinded independent committee. We compared the treatment effect on the primary endpoint and stroke alone based on the investigators' and adjudicators' assessments, and investigated the agreement rate on the stroke endpoint and major hemorrhages.
The hazard ratios (95% confidence interval) for ticagrelor versus aspirin therapy for the primary endpoint were 0.89 (0.78-1.01) when calculated on adjudicator-assessed events and 0.88 (0.78-1.00) for investigator-assessed events. The hazard ratios (95% confidence intervals) for stroke were 0.86 (0.75-0.99) based on the adjudicators' diagnoses and 0.85 (0.75-0.97) based on the investigators' diagnoses. The overall agreement between adjudicator- and investigator-diagnosed stroke was 91%, and for major hemorrhages was 88%.
In SOCRATES, there was no clinically meaningful difference in the estimated treatment effect, on either the primary endpoint or stroke, by using investigator- or adjudicator-assessed events. Double-blind treatment outcome studies with stroke endpoints may not benefit from adjudication.
ClinicalTrials.gov Identifier: NCT01994720.
终点裁定是心血管临床试验中的标准程序。然而，几项研究表明，裁定在估计治疗效果方面的益处可能有限。
本研究对 SOCRATES（NCT01994720）进行了事后分析，比较了治疗效果，并调查了现场研究者和独立裁定者对临床事件评估的一致性。
SOCRATES 比较了替格瑞洛和阿司匹林在 13199 例急性小卒中或高危短暂性脑缺血发作患者中的疗效。主要终点为卒中、心肌梗死或死亡。卒中是主要终点和次要终点的主要组成部分。终点由盲法独立委员会裁定。我们比较了根据研究者和裁定者的评估，对主要终点和单独卒中的治疗效果，并调查了卒中终点和主要出血的一致性。
根据裁定者评估的事件，替格瑞洛与阿司匹林治疗的主要终点的危险比（95%置信区间）为 0.89（0.78-1.01），而根据研究者评估的事件为 0.88（0.78-1.00）。根据裁定者诊断，卒中的危险比（95%置信区间）为 0.86（0.75-0.99），而根据研究者诊断为 0.85（0.75-0.97）。裁定者和研究者诊断的卒中之间的总体一致性为 91%，主要出血为 88%。
在 SOCRATES 中，使用研究者或裁定者评估的事件，在主要终点或卒中方面，估计的治疗效果没有临床意义上的差异。具有卒中终点的双盲治疗结果研究可能不需要裁定。
ClinicalTrials.gov 标识符：NCT01994720。
