The New England Journal of Medicine has been accused of failing its readers and damaging its reputation over a study involving the drug rofecoxib (Vioxx).
The journal waited five years to publish its concerns about the study’s findings, says an editorial published online ahead of print publication in August in the Journal of the Royal Society of Medicine (www.jrsm.org). Had it done so earlier, says the editorial, the dangers of the drug, which was later withdrawn, might have been highlighted sooner.
“The way that the journal has behaved in the dispute around the VIGOR [Vioxx gastrointestinal outcomes research] trial, which was the making of Merck’s drug rofecoxib (Vioxx), has raised doubts about its integrity and dovetailed with a growing anxiety about the ethics of medical journals,” the editorial says.
The editorial’s author, Richard Smith, the former editor of the BMJ , said, “It is unfortunate that the journal waited five years before publishing a correction. Concerns about the correctness of the study were raised with the editor, Jeff Drazen, as early as August 2001, the drug was withdrawn in 2004, and yet it wasn’t until December 2005 that the journal published its first correction. The journal failed its readers. It has damaged its reputation.”
The study, which was published in the journal in November 2000, involved 8000 patients who received naproxen or rofecoxib, a cyclo-oxygenase-2 inhibitor that was expected to have fewer gastrointestinal side effects than naproxen.
The published results showed that patients who were given rofecoxib did have fewer such side effects, and in the United States some 20 million people took the drug before it was eventually withdrawn. The editorial says that Merck bought 900 000 reprints of the article at an estimated cost of up to $836 000 (£450 000; €650 000) to promote the drug.
The trial also showed that the patients who took rofecoxib had a higher risk of myocardial infarction than those who took naproxen, and this was interpreted by the authors as the result of naproxen having a protective effect.
But four years later, in September 2004, Merck withdrew the drug from the market when, says the editorial, it became clear that it had serious cardiovascular side effects (BMJ 2004;329:816).
In December 2005 the New England Journal of Medicine published its expression of concern about the study (2005;353:2813-4), saying that it did not accurately represent the safety data available to the authors when the article was being reviewed for publication. The editorial says that the expression of concern was published because problems had emerged as evidence was being gathered for a court case against Merck by patients alleging that they had been damaged by rofecoxib.
“These data showed that there were 47 confirmed serious thromboembolic events in the patients given rofecoxib and 20 in those given naproxen—so wiping out the gastrointestinal benefits from rofecoxib,” says the editorial, which adds that an additional three cases of myocardial infarction occurred among the patients in the rofecoxib group.
It says, “If all of these data had been included in the original report the interpretation that naproxen was protective rather than rofecoxib harmful would have been much less convincing—indeed, it would probably have been untenable.”
It says that the US Food and Drug Administration had cast doubt on the suggestion that naproxen was protective as early as 2001, as had JAMA .
The issue has been complicated by another correction in the New England Journal of Medicine relating to rofecoxib. This correction, published online ahead of print on 26 June (http://content.nejm.org/, doi:10.1056/NEJMx060029), related to a study published last year, the 2005 colorectal adenoma chemoprevention study. The correction said that an increase in cardiovascular events associated with rofecoxib occurred much earlier in the course of treatment than the study had reported (BMJ 2006;333:12, 1 Jul).
A spokeswoman for the New England Journal of Medicine said neither the journal nor its editor would be commenting.