Journal corrects conclusion of Vioxx risk study
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A critical study showing the heart attack and stroke risk of Merck and Co.‘s now-withdrawn arthritis drug Vioxx contained statistical errors that incorrectly showed that the risk changes over time, The New England Journal of Medicine reported on Monday.
The journal and the authors, including a team at Merck, are issuing a correction to the May 2005 study to show the risks do not, as originally shown, greatly increase after 18 months.
In fact, it is not possible to tell when the risk of heart attack or stroke shoot up, Journal editor Dr. Jeffrey Drazen said.
Merck withdrew Vioxx from the market in September of 2004 after a three-year study showed it doubled the risk of heart attack and strokes in patients who took it for at least 18 months.
Last month, Merck said it was correcting one of the statistical methods used to analyze data from that key study, but said the change did not alter the results of that clinical trial.
But Drazen said the mistake was significant enough to change some of the conclusions of the trial—including the important 18-month cutoff.
“They found this mistake. It turned out they did the wrong math. The proportional hazards calculation in fact was not significant,” Drazen said in a telephone interview.
“You couldn’t make this argument that the hazards weren’t proportionate over time. It meant a lot of their conclusions they had originally drawn no longer could be accepted.”
The correction to the data from the study, called APPROVe, involves statistical and graphical methods used to assess whether the relative risk of Vioxx compared to placebo was constant or if it changed over time.
The statistical re-analysis of the trial was performed by Dr. Stephen W. Lagakos, professor of biostatistics at the Harvard School of Public Health in Boston. Not only did he find that the 18-month cut-off for cardiovascular risk was not statistically significant, he concludes: “One could not conclude from the data that a shorter course of rofecoxib is safe.”
His analysis will be published in the July 13 issue of the Journal.
“Because of the mathematical errors, the editors allowed some statements in the original file which we no longer feel are supported by the weakened evidence,” Drazen said.
Merck is facing more than 11,500 product liability lawsuits from people claiming to have been harmed by Vioxx, which earned $2.5 billion a year before it was withdrawn from the market.
Vioxx, known generically as rofecoxib, is in a class of drugs known as COX-2 inhibitors. These drugs were designed to be safer alternatives to aspirin, ibuprofen and other non-steroidal anti-inflammatory drugs or NSAIDs, which can cause stomach bleeding, which can sometimes be fatal.
Drazen defended the Journal’s handling of the study, which has been criticized. “The papers always said that although it took 18 months for you to appreciate a difference in risk, it didn’t mean you had to be exposed to the drugs for 18 months,” Drazen said.
In other words, a patient could take Vioxx for three months, or six months, and not have the bad side effects until 18 months later.
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