BACKGROUND: In September 2004, rofecoxib was voluntarily withdrawn from the worldwide market. Our objective was to determine whether and when analysis of published and unpublished placebo-controlled trials could have revealed cardiovascular risk associated with rofecoxib before its withdrawal as an example to inform future postmarket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. METHODS: 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. RESULTS: We identified 30 randomized, placebo-controlled trials of rofecoxibthat enrolled a combined 20 152 subjects. Trial duration ranged from 4 weeks to 4 years; enrollment ranged from 17 to 2586 subjects prescribed eitherrofecoxib 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 from a safety standpoint. Subsequently collected data through June 2001 showed that rofecoxib was associated with a 35% increased risk of a CVT adverse event or death (RR, 1.35; 95% CI, 1.00-1.96) (P = .05). Analyzing data available as of April 2002, we found a 39% increased risk (RR, 1.39; 95% CI, 1.07-1.80) (P = .02), and using data available as of September 2004, we found a 43% increased risk (RR,1.43; 95% CI, 1.16-1.76) (P < .001). CONCLUSION: Cumulative pooled analysis of all randomized, placebo-controlled trials demonstrates a trend toward increased cardiovascular risk associated with rofecoxib compared with placebo as early as December 2000, the comparison reaching a P value of .05 by June 2001, nearly 3(1/2) years before the manufacturer's voluntary market withdrawal.
RCT Entities:
BACKGROUND: In September 2004, rofecoxib was voluntarily withdrawn from the worldwide market. Our objective was to determine whether and when analysis of published and unpublished placebo-controlled trials could have revealed cardiovascular risk associated with rofecoxib before its withdrawal as an example to inform future postmarket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. METHODS: 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. RESULTS: 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 from a safety standpoint. Subsequently collected data through June 2001 showed that rofecoxib was associated with a 35% increased risk of a CVT adverse event or death (RR, 1.35; 95% CI, 1.00-1.96) (P = .05). Analyzing data available as of April 2002, we found a 39% increased risk (RR, 1.39; 95% CI, 1.07-1.80) (P = .02), and using data available as of September 2004, we found a 43% increased risk (RR,1.43; 95% CI, 1.16-1.76) (P < .001). CONCLUSION: Cumulative pooled analysis of all randomized, placebo-controlled trials demonstrates a trend toward increased cardiovascular risk associated with rofecoxib compared with placebo as early as December 2000, the comparison reaching a P value of .05 by June 2001, nearly 3(1/2) years before the manufacturer's voluntary market withdrawal.
Authors: R Day; B Morrison; A Luza; O Castaneda; A Strusberg; M Nahir; K B Helgetveit; B Kress; B Daniels; J Bolognese; D Krupa; B Seidenberg; E Ehrich Journal: Arch Intern Med Date: 2000-06-26
Authors: E W Ehrich; T J Schnitzer; H McIlwain; R Levy; F Wolfe; M Weisman; Q Zeng; B Morrison; J Bolognese; B Seidenberg; B J Gertz Journal: J Rheumatol Date: 1999-11 Impact factor: 4.666
Authors: C Bombardier; L Laine; A Reicin; D Shapiro; R Burgos-Vargas; B Davis; R Day; M B Ferraz; C J Hawkey; M C Hochberg; T K Kvien; T J Schnitzer Journal: N Engl J Med Date: 2000-11-23 Impact factor: 91.245
Authors: C Hawkey; L Laine; T Simon; A Beaulieu; J Maldonado-Cocco; E Acevedo; A Shahane; H Quan; J Bolognese; E Mortensen Journal: Arthritis Rheum Date: 2000-02
Authors: Alan J Kivitz; Maria W Greenwald; Stanley B Cohen; Adam B Polis; Daryl K Najarian; Mary E Dixon; Robert A Moidel; Jerry A Green; Herbert S B Baraf; Richard A Petruschke; Alan K Matsumoto; Gregory P Geba Journal: J Am Geriatr Soc Date: 2004-05 Impact factor: 5.562
Authors: John A Baron; Robert S Sandler; Robert S Bresalier; Angel Lanas; Dion G Morton; Robert Riddell; Erik R Iverson; David L Demets Journal: Lancet Date: 2008-10-14 Impact factor: 79.321
Authors: Gudrun Stefansdottir; Marie L De Bruin; Mirjam J Knol; Diederick E Grobbee; Hubert G M Leufkens Journal: Drug Saf Date: 2011-09-01 Impact factor: 5.606