Pooled analysis of rofecoxib placebo-controlled clinical trial data: lessons for postmarket pharmaceutical safety surveillance.

Archives of Internal Medicine
Joseph S RossHarlan M Krumholz

Abstract

In September 2004, rofecoxib was voluntarily withdrawn from the worldwide market. Our objective was to determine whether and when analysis of published and unpublished placebo-controlled trials could have revealed cardiovascular risk associated with rofecoxib before its withdrawal as an example to inform future postmarket pharmaceutical safety surveillance efforts. We conducted a cumulative subject-level pooled analysis of data from all randomized, placebo-controlled trials of rofecoxib conducted by the manufacturer before September 2004. Our main outcome measurement was incidence of any investigator-reported death from any cause or cardiovascular thromboembolic (CVT) adverse event. We identified 30 randomized, placebo-controlled trials of rofecoxib that enrolled a combined 20 152 subjects. Trial duration ranged from 4 weeks to 4 years; enrollment ranged from 17 to 2586 subjects prescribed either rofecoxib or placebo; and rofecoxib dose ranged from 12.5 mg to 50 mg. As of December 2000, 21 of these trials had been completed (70%), and the risk of a CVT adverse event or death was greater among subjects assigned to the rofecoxib group (rate ratio [RR], 2.18; 95% confidence interval [CI], 0.93-5.81) (P = .07), raising concerns fro...Continue Reading

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Citations

May 31, 2011·International Journal of Occupational and Environmental Health·David S Egilman, Nicholas M Druar
Dec 15, 2010·Archives of Internal Medicine·Joseph S RossHarlan M Krumholz
Oct 13, 2011·JAMA : the Journal of the American Medical Association·Harlan M Krumholz, Joseph S Ross
Nov 19, 2011·American Journal of Public Health·Joseph S RossHarlan M Krumholz
Feb 12, 2010·The New England Journal of Medicine·John HohnekerGabriela Gruia
Dec 10, 2014·Expert Review of Clinical Pharmacology·Vaishali K PatadiaUNKNOWN EU-ADR consortium
Jun 30, 2012·Revue neurologique·F Abou-MradJ Feingold
Apr 24, 2012·Social Science & Medicine·Mary WiktorowiczKathy Moscou
Aug 11, 2012·American Heart Journal·David MadiganJerry Avorn
Aug 31, 2016·Expert Review of Clinical Pharmacology·Gerhard ZinglerThomas Herdegen
Jun 14, 2010·Pharmaceuticals·Maria Antonietta Ajmone-CatLuisa Minghetti
Sep 24, 2015·Circulation·Joseph S Ross, Aaron S Kesselheim
Mar 23, 2012·Circulation. Cardiovascular Quality and Outcomes·Harlan M Krumholz
Mar 23, 2012·Circulation. Cardiovascular Quality and Outcomes·Joseph S RossCary P Gross
Jan 17, 2012·Clinical Rheumatology·Boulos HaraouiKim A Papp
Oct 29, 2019·JAMA Internal Medicine·Alexander C EgilmanAmy Kapczynski
Feb 9, 2012·Pharmacoepidemiology and Drug Safety·Preciosa M ColomaUNKNOWN EU-ADR Consortium
Mar 10, 2010·Medical Oncology·Derek G Power, Nancy E Kemeny
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Nov 1, 2015·European Heart Journal. Quality of Care & Clinical Outcomes·Huseyin NaciElias Mossialos
Nov 25, 2017·Pharmacoepidemiology and Drug Safety·Michèle BallyJames M Brophy
Mar 25, 2016·Journal of Cardiovascular Pharmacology and Therapeutics·Juan Ruiz-Garcia, Eduardo Alegria-Barrero

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