Article Questions Need for Revision of Vioxx Study Report

A new article from Bloomberg reports that changes may have to be made to an Annals of Internal Medicine article linking Vioxx to heart problems.

Here is the complete article.

Tuesday, May 3, 2005


The Annals of Internal Medicine may publish a correction to a Merck & Co.-sponsored study of the pain pill Vioxx to show the drug had a higher risk of heart attacks than originally stated, journal editor Harold Sox said.
The study, published in 2003, listed five heart attacks among arthritis patients taking Vioxx compared with one in those taking naproxen. Three additional cardiac deaths in the Vioxx group went unmentioned, including one in which company officials may have pressured a researcher to change his opinion about the likely cause of death, the New York Times reported on April 24.

“Corrections happen all the time, but corrections that materially change the message of the article are pretty uncommon,” Sox said in a telephone interview April 27. “If they had told us it was 8-to-1, it would have been much different than 5-to-1.”

Merck, the third-largest U.S. drugmaker, says it had no definitive evidence of Vioxx’s heart risks until right before it pulled the $2.5 billion-a-year drug in September 2004 in the largest drug recall ever. Some doctors, lawmakers and plaintiffs have said the Whitehouse Station-based company should have known before then that Vioxx might be dangerous.
Sox said he learned that the trial results he published might have been manipulated when he opened his New York Times on April 24. He met with his editorial staff the following day and posted a notice on the magazine’s Web site notifying readers the staff was considering a correction.

“Basically, we want to find out, did those patients really have a heart attack or not,” Sox, who is also a physician, said in the interview last week. He hopes to have an answer within the month.

Merck spokeswoman Jeanine Clemente said in an e-mailed statement Monday that the study doesn’t need to be corrected and the company would be happy to discuss any concerns the journal editors may have. On April 24, Merck spokeswoman Cynthia Smith told Bloomberg News that Merck submitted the results of the research, including data on adverse effects regardless of whether they were classified as cardiovascular, promptly to the U.S. Food and Drug Administration.

The Annals editors plan to contact Jeffrey Lisse, the study’s author, before determining whether to run a correction, said Sox. Lisse, a rheumatologist at |the University of Arizona, was quoted in the Times story as saying that while he is listed as the study’s author, Merck actually wrote the report.
Lisse did not return a call to his office seeking comment.
Merck shares rose 10 cents to $34 at 4:01 p.m. in New York Stock Exchange composite trading. They have fallen 25 percent since the Vioxx recall was announced. As of March 31, Merck was the subject of about 2,300 lawsuits from 4,600 plaintiffs’ groups alleging personal injury from Vioxx.

The study in question, called Advantage, sought to show that Vioxx was easier on the stomach than the older painkiller naproxen, sold in pharmacies under the brand name Aleve. The 12- week trial involved about 5,500 arthritis patients taking either 25 mg of Vioxx or 100 mg of naproxen. The study was completed in 2000.
Merck overruled a suggestion by one of its researchers that a 73-year-old woman participating in the study probably died of a heart attack, the New York Times reported, citing documents provided by a person working with plaintiffs.
The cause of death was eventually listed as “unknown,” the newspaper said, adding that FDA reviewer Maria Lourdes Villalba concluded in a November 2001 report that Merck had misclassified the woman’s death.