Dec. 9, 2005 -- U.S. doctors were upset to learn that the authors of a 2000 study funded by the pharmaceutical giant Merck possibly failed to disclose data that three additional patients suffered heart attacks while using Merck's popular painkiller, Vioxx.
The new cases were made public in a New England Journal of Medicine editorial on Thursday. According to the Associated Press, data in Thursday's editorial show that 20 patients on Vioxx suffered heart attacks, instead of the 17 originally reported. Among patients in a comparison group taking naproxen, an over-the-counter pain medication, there were four heart attacks.
Dr. Claire Bombardier, a prominent rheumatologist at Toronto's Mount Sinai Hospital who was the lead author of the study, defended the data submitted by the team in an e-mail to The Associated Press, saying it "appropriately disclosed the data as per the pre-specified plan of analysis."
Doctors rely on the medical journals to publish studies about patient trends and treatments. When that information is incorrect, it can have dire consequences, many doctors noted.
"The honesty of authors and the accuracy of journal is vital to the bona fide practice of medicine," said University of Wisconsin family medical professor Bill Cayley in an email interview. "Evidence-based medicine, which should be the standard of care, is about applying the best available evidence to the care of individual patients. If we cannot trust the veracity of published data, or the process by which it comes to be published, then we do not have sound footing."
Physician Patricia Clancy agreed.
"I have no other way to evaluate data," said Clancy, of Concord, New Hampshire. "I rely on [journals] to help sift through biased data and exclude it."
In 2000, the journal published the results of the "VIGOR" trial, which compared the gastrointestinal side effects of Vioxx with naproxen.
Following publication, Vioxx became widely prescribed for people in need of pain relief but who were at risk of stomach irritation from more common drugs. Eventually, though, further studies and other reports began to uncover that Vioxx might increase the risk of a heart attack, and the drug was pulled from the market last year.
The drug's manufacturer, Merck, is currently involved in several law suits about the possible heart attack risk. At least another 7,000 have been filed, according to the Associated Press.
The journal's executive editor, Dr. Gregory D. Curfman, said he learned of the extra heart attacks when he gave a deposition on Nov. 21 for attorneys representing Vioxx plaintiffs in a Houston trial and three other federal trials slated for early next year.
The company released a statement yesterday about the journal's allegations, stating "these additional events were disclosed to the FDA in 2000, presented publicly at the FDA's Advisory Committee in February 2001, included in numerous press releases subsequently issued by Merck, disclosed to physicians given a copy of the article by Merck and detailed in the updated prescribing information for VIOXX. We also note that these additional events did not materially change any of the conclusions in the article."
Pharmacist Brian Kawahara said that it's not unusual for adverse effects to occur after the clinical trial has concluded. When the drug is approved and then used widely by the American public, even more side effects may crop up.
"Most studies are so short that the manufacturer has no idea of the long-term issues associated with the drug," said Kawahara, of Loma Linda, Calif. "In many cases, an older [drug] may be a better therapy."
When drug companies have a clear financial stake in the results of the study, it may be appealing for them to mask or misinterpret results, noted family physician Lee Green of the University of Michigan.
"The only way we'll ever get trustworthy, unbiased research on commercial products is to ensure that those whose profits are at stake have no say in the funding, design, conduct, analysis or publication of the research," Green said.
Ideally, the editors of medical journals are suppose to analyze studies for any potential conflicts, especially when a drug company has supported a study being submitted for publication. In this case, the editors of the New England Journal of Medicine may have some part to play in the matter, said Dr. William Golden, a medical and public health professor at the University of Arkansas.
Although the editors have asked Merck to submit a correction to the VIGOR study, that doesn't mean the journal should not receive some of the blame, Golden said.
"Their unprecedented editorial may reflect an attempt at assuaging their own guilt about being part of this debacle," he said.