Kittle Jessie, Lopes Renato D, Huang Mingyan, Marquess Marsha L, Wilson Matthew D, Ascher John, Krishen Alok, Hasselblad Vic, Kolls Brad J, Roe Matthew T, McGuire Darren K, Russell Stuart D, Mahaffey Kenneth W
Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Stanford, California.
Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina.
Clin Cardiol. 2017 Oct;40(10):899-906. doi: 10.1002/clc.22744. Epub 2017 Jun 12.
In 2011, the US Food and Drug Administration requested that GlaxoSmithKline perform retrospective adjudication of cardiovascular (CV) events reported in the bupropion drug-development trials for smoking cessation.
Retrospective adjudication of clinical trial data will not increase the identification of adverse events.
We performed a comprehensive retrospective analysis of adverse events in 19 previously completed controlled US clinical trials of bupropion marketed for the treatment of smoking cessation, yielding 9479 subjects (5290 bupropion, 2927 placebo, 1018 active control [ACT], and 244 treated concurrently with bupropion and ACT). All adverse events were sent to the Duke Clinical Research Institute for adjudication by Clinical Events Classification (CEC) physician reviewers. The primary endpoint was a composite of major adverse CV events: CV death, nonfatal myocardial infarction (MI), and nonfatal stroke.
Overall, 416 nonfatal CV events in 366 subjects, and 22 deaths, were identified and processed for adjudication. Of these, 7 nonfatal MIs (4 bupropion, 3 placebo, 0 ACT), 5 nonfatal strokes (1 bupropion, 3 placebo, 1 ACT), and 9 CV deaths (4 bupropion, 4 placebo, 1 ACT) were confirmed by the CEC Committee. The primary endpoint occurred in 3/4297 (0.07%) subjects in the bupropion group and in 4/2927 (0.14%) subjects in the placebo group (log-rank P value: 0.613).
CV events in bupropion clinical trials for smoking cessation were uncommon, with no observed increase among subjects assigned to bupropion vs placebo. However, this effort was limited by a paucity of quality data.
2011年，美国食品药品监督管理局要求葛兰素史克公司对安非他酮戒烟药物研发试验中报告的心血管（CV）事件进行回顾性判定。
对临床试验数据进行回顾性判定不会增加不良事件的识别。
我们对19项先前完成的、在美国进行的、用于治疗戒烟的安非他酮对照临床试验中的不良事件进行了全面的回顾性分析，涉及9479名受试者（5290名服用安非他酮、2927名服用安慰剂、1018名服用活性对照药[ACT]以及244名同时服用安非他酮和ACT）。所有不良事件均被送至杜克临床研究所，由临床事件分类（CEC）医师评审员进行判定。主要终点是主要不良心血管事件的复合指标：心血管死亡、非致命性心肌梗死（MI）和非致命性中风。
总体而言，共识别出366名受试者的416起非致命性心血管事件以及22例死亡，并进行了判定处理。其中，CEC委员会确认了7起非致命性心肌梗死（4例服用安非他酮、3例服用安慰剂、0例服用ACT）、5起非致命性中风（1例服用安非他酮、3例服用安慰剂、1例服用ACT）以及9例心血管死亡（4例服用安非他酮、4例服用安慰剂、1例服用ACT）。主要终点事件在安非他酮组的3/4297（0.07%）受试者中发生，在安慰剂组的4/2927（0.14%）受试者中发生（对数秩检验P值：0.613）。
安非他酮戒烟临床试验中的心血管事件并不常见，与安慰剂组相比，服用安非他酮的受试者中未观察到心血管事件增加。然而，这项研究受到了高质量数据匮乏的限制。
