@article{7c31dc7f63f6489dab3ce8a592989e09,
title = "Cardiovascular adverse events in the drug-development program of bupropion for smoking cessation: A systematic retrospective adjudication effort",
abstract = "Background: 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. Hypothesis: Retrospective adjudication of clinical trial data will not increase the identification of adverse events. Methods: 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. Results: 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). Conclusions: 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.",
keywords = "Adjudication, Adverse Cardiovascular Events, Bupropion, Smoking Cessation, Systematic Review",
author = "Jessie Kittle and Lopes, {Renato D.} and Mingyan Huang and Marquess, {Marsha L.} and Wilson, {Matthew D.} and John Ascher and Alok Krishen and Vic Hasselblad and Kolls, {Brad J.} and Roe, {Matthew T.} and McGuire, {Darren K.} and Russell, {Stuart D.} and Mahaffey, {Kenneth W.}",
note = "Funding Information: The Bupropion CV Adjudication Study was sponsored by GSK under contract with the DCRI. GSK was solely responsible for the search of all bupropion studies, identification of all potential events, and shipment of event packets with all available supporting documents to DCRI. GSK wrote the analysis plan. DCRI wrote the CEC charter documenting the CEC process to be used, identified and trained the physician reviewers, and performed all event adjudications, without GSK involvement. GSK did approve the CEC charter, the proposed endpoint definitions, and the physician reviewers. Funding Information: RDL reports receiving consulting fees and research grants from Bristol-Myers Squibb, research grants from GlaxoSmithKline, and consulting fees from Boehringer-Ingelheim, Bayer, and Pfizer. JA and AK were employees of GlaxoSmithKline at the time of this study. MTR reports receiving personal fees from AstraZeneca, grants and personal fees from Eli Lilly, personal fees from Merck and Co., grants and personal fees from Janssen, grants from Sanofi-Aventis, grants from Daiichi-Sankyo, personal fees from Elsevier Publishers, personal fees from Amgen, grants from Familial Hypercholesterolemia Foundation, personal fees from Bristol-Myers Squibb, personal fees from Boehringer-Ingelheim, grants from Ferring Pharmaceuticals, personal fees from PriMed, grants from Kai Pharmaceuticals, and personal fees from Regeneron. DKM has received personal fees from Boehringer-Ingelheim, Janssen Research and Development LLC, Sanofi-Aventis Group, Genentech, Inc., Merck Sharp and Dohme, Daiichi-Sankyo, Inc., Lilly USA, Novo Nordisk, GlaxoSmithKline, Takeda Pharmaceuticals North America, Bristol-Myers Squibb, AstraZeneca, Orexigen, Lexicon, Eisai, Regeneron, Janssen, Boehringer-Ingelheim, Merck, Pfizer, and Genfit, personal fees from University of Oxford, Duke Clinical Research Institute, Partners Healthcare, and the Cleveland Clinic Foundation, and non-financial support from Gilead Sciences. KWM{\textquoteright}s financial disclosures can be viewed at http://med.stanford.edu/ profiles/kenneth-mahaffey. The authors declare no other potential conflicts of interest. Publisher Copyright: {\textcopyright} 2017 Wiley Periodicals, Inc.",
year = "2017",
month = oct,
doi = "10.1002/clc.22744",
language = "English (US)",
volume = "40",
pages = "899--906",
journal = "Clinical Cardiology",
issn = "0160-9289",
publisher = "John Wiley and Sons Inc.",
number = "10",
}