THURSDAY, Dec. 8, 2005 (HealthDay News) -- The editors at one of the world's leading medical journals have accused researchers and Vioxx manufacturer Merck & Co. of withholding key heart risk data that showed up in one of the first large trials of the now-withdrawn arthritis painkiller.
Specifically, the editors of the New England Journal of Medicine charged that a major study published in November 2000 was submitted to the journal after information about three heart attacks among Vioxx trial participants was deleted by Merck, which funded the study.
Dr. Gregory D. Curfman, executive editor of the journal, told HealthDay, "We have very solid evidence that important data on cardiac events was deleted or withheld, which rendered the study of suboptimal quality."
"The three additional heart attacks were all in people taking Vioxx who were at low risk," he added. "It changes the level of risk and changes one of the conclusions [of the study] that only people at high risk were at risk."
In addition, electronic records showed "a pre-submission version of the study from which data, including the number of heart attacks and deaths, were deleted by a Merck editor two days before submission," Curfman told HealthDay.
The Associated Press quotes a Merck statement made late Thursday that asserts the additional heart attacks "did not materially change any of the conclusions of the article." According to the A.P., Merck also said the additional heart attack data was not included because the heart attacks were reported after Merck's cut-off date for including study data.
Curfman, along with the journal's editor-in-chief, Dr. Jeffrey M. Drazen, raised the issues in a formal "Expression of Concern" printed as an editorial in the Dec. 29 issue of the journal. An expression of concern is the procedure established by the International Committee of Medical Journal Editors (ICMJE) for announcing concern about the validity of previously published work.
Despite its publication date, the unusual accusation was released Thursday afternoon just as jurors in Houston began their deliberations in the first federal trial against Merck involving the drug. The widow of a 53-year-old Florida man is suing the drug company, claming the drug caused her husband's fatal heart attack.
Vioxx was taken off the market in September 2004 after research showed that long-term use of the drug doubled the risk of heart attack and stroke.
The study now questioned by the journal editors was called VIGOR (Vioxx Gastrointestinal Outcomes Research), and its conclusions had been frequently cited by Merck in the current trial and elsewhere as proof of Vioxx's safety. The study was led by Dr. Claire Bombardier, of the Institute for Work and Health, Mount Sinai Hospital, and University Health Network, in Toronto. Efforts by HealthDay to reach her for comment were unsuccessful.
The VIGOR trial, involving 8,076 patients at 301 centers in 22 countries, was designed to compare gastrointestinal problems in patients with rheumatoid arthritis when they took Vioxx, a cox-2 inhibitor, vs. naproxen (Naprosyn). The authors of the study concluded that Vioxx was associated with significantly fewer important upper gastrointestinal events than naproxen.
In addition, the researchers monitored information on cardiovascular events and found that heart attacks were less common in the naproxen group (0.1 percent vs. 0.4 percent). But if patients who should have been taking aspirin -- but weren't -- were excluded, the difference in heart attacks between the two groups was not significant, they concluded.
The editors of the New England Journal said they had first became aware of the missing heart attack data in 2001, when updated data was made available by the U.S. Food and Drug Administration.
They did not, however, think the VIGOR authors had known about them in time for the study's publication.
Fast forward to the current litigation surrounding Vioxx.
As the Vioxx trial in Houston moved along, the third against Merck so far, the plaintiff's attorneys subpoenaed Curfman, the journal's executive editor. He was deposed on Nov. 21.
During this process, the contents of a memorandum dated July 5, 2000, came to light. The memo indicated that at least two of the three VIGOR authors knew of the problems at least two weeks before submitting the first of two revisions, and four-and-a-half months before actual publication, of the study.
Further investigation revealed that the authors had originally known of the data.
When the study manuscript was first submitted to journal editors, the journal was making the transition from paper to electronic handling, the editors said in an accompanying statement to their editorial. The document was submitted both on paper and on a computer diskette, but the editing process took place only on paper.
No one looked at the disk until Oct. 5, 2004, just days after Vioxx was withdrawn from the market.
In addition to the disk deletions, Curfman said, when the July memorandum came out, "other data relating to strokes and peripheral vascular events had also been withheld. It would have given a more complete picture of the risks of Vioxx. That would have made the data more worrisome."
The journal editors have asked the authors to submit a correction.
In the study published Nov. 23, 2000, in the journal, 10 of the 12 VIGOR authors were listed in the disclosure section as having received clinical research support from Merck. One of the two authors not listed in that section was Dr. Alise Reicin, who was a Merck research executive then and is now Merck's vice president for clinical research.
In the Houston trial, now in the hands of the jury, Reicin testified on Wednesday that the company had never misled doctors and the public about studies linking heart attacks to Vioxx, according to news reports.
More information
The U.S. Food and Drug Administration has more on Vioxx and other medications in that class.
