DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more



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

Author(s): Ross JS, Madigan D, Hill KP, Egilman DS, Wang Y, Krumholz HM

Affiliation(s): Department of Geriatrics and Palliative Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1070, New York, NY 10029, USA. joseph.ross@mssm.edu

Publication date & source: 2009-11-23, Arch Intern Med., 169(21):1976-85.

Publication type: Comment; Meta-Analysis; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

BACKGROUND: In September 2004, rofecoxib was voluntarily withdrawn from the worldwide market. Our objective was to determine whether and when analysis of published and unpublished placebo-controlled trials could have revealed cardiovascular risk associated with rofecoxib before its withdrawal as an example to inform future postmarket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.

Page last updated: 2010-10-05

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017