NEJM Published Additional Criticism Of Vioxx Study. The editors of the New England Journal of Medicine published additional criticism of a Vioxx study on Wednesday, even as it allowed the authors of the article to defend themselves against the critique it delivered two months ago.
In the latest salvo, the editors said that if the authors had disclosed all heart-related side effects patients suffered by taking Vioxx in the study originally published in 2000, it would have shown that any complicated gastrointestinal event the drug prevented was offset by a serious heart problem.
Vioxx was developed to be gentler on the stomach than other pain relievers, which accounted for much of its consumer appeal. Merck & Co. removed it from the market in September 2004 after a study showed it doubled the risk of heart attacks and strokes after 18 months of use.
In a statement, Merck said that it stood firmly behind the analysis and data in the Vigor publication.
The latest criticism expands on an “Expression of Concern” the Journal published two months ago. That letter said that at least two authors knew about three additional heart attacks suffered by patients taking Vioxx 4 1/2 months before the study results were published.
It said the failure to disclose information made the article’s calculations and conclusions incorrect. Furthermore, the Journal said the some of the data were deleted from the manuscript two days before it was submitted in May 2000.
Two letters to the editor were submitted to the Journal to address the criticisms: One by Merck-employed scientists and the other by the 11 non-Merck authors.
Both letters said the handling of the data was appropriate and that it would have been a breach of scientific protocol to report the heart attacks because they occurred after a specified cutoff data. They also both said the additional heart attacks didn’t materially affect the outcome of the study.
Patients Taking Vioxx Had A High Rates Of Heart Attacks
Without the additional heart attacks, the study found that patients taking Vioxx had four times the rate of heart attacks of those taking a comparative drug, naproxen. If the three heart attacks are added, the rate rises to five times the rate of heart attacks.
Phil Beck, a Merck attorney who won a federal Vioxx case last week, questioned why the Journal chose to highlight information in Wednesday’s editorial that had not been included in the original statement.
“I don’t know why this was not significant the first time but all of a sudden is significant,” Beck said.
Beck said the data the Journal presented has been known to the FDA for years and was included on the drug’s label. He added that the authors were not given an opportunity to respond to the latest charges just as they hadn’t been in the first criticism.
In a statement, the Journal said it asked the authors to address issues that transcended the original expression of concern. The Journal said its questions weren’t fully answered so it opted to publish additional data and details about cardiovascular events that it believed should have been included in the original article.
Dr. Claire Bombardier, lead author of the Vigor study, said the Journal didn’t ask about issues beyond matters touched on in the December letter.
“This process differs from normal scientific exchange and it is regrettable,” Bombardier said.
The focus of the latest editorial goes beyond looking at how the heart attacks affected the study’s outcome. It says that at least two authors of the study “were aware of a critical data on an array of adverse cardiovascular events” more than four months before the article was published.
The Journal published tables that include additional types of heart-related problems such as hemorrhagic strokes and peripheral venous thrombosis which it said it didn’t have in 2000. All the data were reported to the U.S. Food and Drug Administration, and published on Merck’s Web site three months after the article was published, the editorial said.
But the Journal said that “because these data were not included in the published article, conclusions regarding the safety of rofecoxib (Vioxx) were misleading.”
Merck faces over 9,000 Vioxx-related suits. It has won two trials and lost another. A fourth is ongoing in Texas and a fifth is slated to start in New Jersey next week.