The New England Journal of Medicine publicly alleged Thursday at least two of the authors of a major Canadian-led study on the former blockbuster drug Vioxx withheld data on adverse events from the journal.
In a stinging editorial released online, the prestigious journal did not specify which of the study authors withheld the information.
But Dr. Gregory Curfman, executive editor of the journal, revealed in an interview that the two were employees of Merck & Co., the company which made the drug and funded the study.
Dr. Alise Reicin, Merck's vice-president for clinical research and Deborah Shapiro, were the only Merck employees among the 12 authors of the study, published in the Nov. 23, 2000 issue of the journal.
The lead author of the study was Dr. Claire Bombardier, a prominent rheumatologist at Toronto's Mount Sinai Hospital. She defended the data disclosure in an e-mail exchange Thursday.
"I believe that the VIGOR paper appropriately disclosed the data as per the pre-specified plan of analysis," Dr. Bombardier insisted.
Dr. Curfman said the journal hoped the editorial would serve as a warning of what happens when researchers ignore their responsibility to report honestly and fully.
"We hope by issuing the statement of concern that it will be a stark reminder to the science community, to the scholarly community, that if we don't have this principle of trust, that the whole scholarly process is just going to collapse into rubble," he said.
The discrepancy came to light when Dr. Curfman recently gave a deposition in a case brought against Merck by the widow of a man who died while taking Vioxx.
In the process, he recently received a memo written by one of the Merck authors to the other Merck author about the study. The memo indicated both knew months before publication of three additional heart attacks that hadn't been factored in to the study findings.
The memo was dated July 5, 2000 — two weeks before the authors submitted the first of two sets of revisions to the journal.
"So we know that both Merck authors had knowledge of the contents of this memo on July 5 and there was quite a lot of information in there about cardiovascular end points," Dr. Curfman said.
And what of Bombardier and the other authors?
"At the very least, it would give the appearance that there wasn't a really good process for how they dealt with the manuscript," Dr. Curfman said.
The editorial, which Dr. Curfman co-authored with the journal's editor-in-chief and managing editor, also charged that other relevant adverse cardiovascular events were deleted from the original manuscript two days before it was submitted for publication.
Analysis of a computer diskette containing the study revealed those changes were made on a Merck computer, Dr. Curfman said.
Withholding the data had the effect of downplaying the already significant difference in cardiovascular risks between Vioxx and naproxen, a generic pain relief medication to which Vioxx was being compared in the study, the journal said.
"Taken together, these inaccuracies and deletions call into question the integrity of the data on adverse cardiovascular events in this article," stated the editorial, titled an Expression of Concern.
"We have asked the authors to submit a correction to the journal."
The journal told the authors of its concerns last Monday, but did not offer to let them issue their response at the same time as the editorial, Dr. Curfman said.
Bombardier said the authors were only informed at noon on Thursday that the journal was releasing the editorial. It was placed on the journal's website three hours later.
"The authors of the paper will be preparing a response to the editorial but have not had the time to finalize it yet," she said.
