An influential medical journal accused Merck yesterday of misrepresenting the results of a crucial clinical trial of the painkiller Vioxx to play down its heart risks.
In a statement last evening, Merck denied that it had acted improperly.
The New England Journal of Medicine’s allegation could play a critical role in the thousands of lawsuits that Merck faces over Vioxx, an arthritis and pain drug.
Vioxx was taken by an estimated 20 million Americans before the company withdrew it last year after a study linked it to heart attacks and strokes. In the three lawsuits that have reached trial so far, Merck has said that it promptly disclosed information about Vioxx’s heart risks.
But in an interview yesterday, Dr. Gregory D. Curfman, the journal’s executive editor, sharply criticized Merck for the way it presented data from the clinical trial. The study, called Vigor, covered more than 8,000 patients and was published in the journal in November 2000, almost four years before Merck stopped selling the drug.
“They did not disclose all they knew,” Dr. Curfman said. “There were serious negative consequences for the public health as a result of that.”
In criticizing Merck and the studies authors at a time when the company’s credibility is at issue in lawsuits, the journal is taking an extraordinary step. The publication is well respected and widely read by doctors and scientists, with a circulation of almost 200,000.
Merck said in its statement that it had acted properly and promptly disclosed the results of the Vigor study, which found that the drug was more likely to cause heart problems than another pain drug. The November 2000 article “fairly and accurately described the results of the study,” the company said.
But Dr. Curfman said the studies authors had originally included some data unfavorable to Vioxx, then deleted it. Lawyers for plaintiffs said they believed that the journal’s allegation would undercut the company’s defense.
Shares of Merck fell almost 5 percent yesterday after the journal published the editorial and a separate statement on its Web site (nejm.org) criticizing the company’s behavior.
In the editorial, “Expression of Concern,” the journal said that the authors of the study had deleted some data about strokes and other vascular problems suffered by patients in the Vigor trial two days before it submitted the results to the publication.
The authors, some of whom worked for Merck, also underreported the number of heart attacks suffered by patients taking Vioxx, claiming that there were 17 heart attacks when there were actually 20, the journal said. The authors have been asked to correct the study, the journal said.
The authors of the Vigor study included independent researchers and Merck scientists, among them Dr. Alise Reicin, who has been a crucial figure in the company’s courtroom defense. The studies results showed that patients taking Vioxx were four times as likely to suffer heart attacks as those taking naproxen, an older painkiller, which is known by the brand name Aleve. In fact, 20 patients taking Vioxx suffered heart attacks, compared with 4 taking naproxen, a ratio of five-to-one.
Merck said at the time that the difference probably resulted from the fact that naproxen protected people from heart attacks, not because Vioxx caused them. Many independent scientists disputed the company’s theory.
If the authors had published the full data about strokes and other vascular problems, the company’s theory would have been even harder to accept, Dr. Curfman said.
“The totality of the data didn’t look good for Vioxx,” he said.
Merck has said it had no clear evidence of Vioxx’s cardiovascular dangers until a clinical trial last year indicated a heightened risk of heart attacks and strokes among patients taking the drug 18 months or longer. It was after those findings that Merck pulled Vioxx off the market in September 2004.
Merck now faces more than 6,000 lawsuits from people who say they or their family members suffered heart attacks and strokes as a result of taking Vioxx, and tens of thousands more lawsuits are expected. The two cases that have been decided so far have resulted in one victory for Merck and one for a plaintiff. Jurors in Federal District Court in Houston yesterday began deliberations in the third case to reach trial.
Christopher Seeger, who represented plaintiffs in the second trial – a victory for Merck in New Jersey state court in Atlantic City – said that he believed that the journal’s allegations would make jurors less likely to trust the company.
“It’s going to alter the landscape of the litigation,” Mr. Seeger said. “They’re accusing Merck of scientific misconduct.”
Last month, a lawyer who represents people suing Merck showed Dr. Curfman a memo from July 2000 between Dr. Reicin and another Merck scientist, Dr. Deborah Shapiro. That memo showed that Dr. Reicin and Dr. Shapiro knew of the three additional heart attack deaths in the Vigor trial well before the journal published the results, Dr. Curfman said. Those heart attacks could and should have been included in the article, he said.
In its statement, Merck said that three additional heart attacks “did not materially change any of the conclusions in the article.” Merck shares, which traded around $30.20 before the journal posted its comments at 3:30 p.m., fell to $28.75 in extended after-hours trading. The stock has fallen almost 40 percent since Merck withdrew Vioxx.
The memo also shows that Dr. Reicin and Dr. Shapiro knew of strokes and serious vascular problems suffered by patients taking Vioxx, Dr. Curfman said.
Dr. Curfman said that, separately, he and other editors had examined the diskette on which the article was sent to the journal and found that the studies authors deliberately removed information about strokes and vascular problems two days before they submitted the study.
“There was some methodical editing of the manuscript to remove data,” he said.
The information in the memo appears to contradict extensive testimony that Dr. Reicin gave in July in Angleton, Tex., in the first Vioxx suit to reach trial, said W. Mark Lanier, the plaintiff’s lawyer in that case. Dr. Reicin should be investigated for perjury for her testimony, Mr. Lanier said.
“It totally destroys Reicin as a witness,” Mr. Lanier said. “I think her testimony in the past is going to really come back and bite her.”
Kent Jarrell, a spokesman for Merck, said the company could not comment on Mr. Lanier’s allegations because of the Vioxx suit in Houston. The judge in that case has prohibited both sides from providing information to the press.
Dr. Curfman said the journal had asked the independent authors on the Vigor article for a correction on Monday, but they had not responded.
In its statement, Merck said it had learned “only recently” of the journal’s editorial and looked forward to offering a more complete response.