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Healthy Skepticism Library item: 2862

Warning: This library includes all items relevant to health product marketing that we are aware of regardless of quality. Often we do not agree with all or part of the contents.

 

Publication type: news

Langreth L, Herper M.
Merck's Deleted Data
Forbes.com 2005 Dec 8
http://www.forbes.com/technology/sciences/2005/12/08/merck-vioxx-lawsuits_cx_mh_1208vioxx.html


Notes:

Ralph Faggotter’s Comments:

The average doctor would assume that any research published in such an esteemed medical journal as the New England Journal of Medicine would be thouroughly checked and guaranteed accurate.

Read this article and think again!

In answer to the critical question: When did Merck first know that Vioxx could cause heart attacks?

—the answer now appears to be, prior to mid-2000 and possibly much earlier.


Full text:

Merck’s Deleted Data
Robert Langreth and Matthew Herper, 12.08.05, 8:10 PM ET

NEW YORK – A top editor of The New England Journal of Medicine says that he was stunned to find out that data linking Vioxx to cardiovascular risk was deleted from a major study his journal published five years ago—and that it appears that Merck researchers may have deleted that data.

“I was somewhere between surprised and stunned,” Dr. Gregory Curfman, executive editor of The Journal, says. “They allowed us to publish an article that was just incomplete and inaccurate in some respects and was misleading and may have contributed to the detriment to the public health.”

The discovery (see: “Merck’s Slanted Study?”) comes as the company faces a flood of lawsuits following its decision to pull the drug from the market in September 2004. Merck recalled Vioxx after its own study linked long-term use of the drug to an increased risk of heart attacks and strokes. Now, the question is if that alarm should have been sounded much earlier.

Just days after Merck recalled Vioxx from the market, editors at The Journal discovered a diskette containing earlier versions of a manuscript for a crucial Vioxx clinical trial called VIGOR that they had published in November 2000.

The early versions of the manuscript contained a blank table entitled “CV events”—which is standard jargon for cardiovascular events. Time stamps in the software indicated that the table was deleted two days before the manuscript was submitted to The New England Journal on May 18, 2000. “When you hover the cursor over the editing changes, the identity of the editor pops up, and it just says ‘Merck,’” Curfman says.

The editors weren’t sure what to make of the finding, so they kept quiet. It wasn’t clear that the information that had been in the table would have changed the conclusions of the study. The published version of the study noted a higher heart attack rate in patients who took Vioxx compared with those who took naproxen, an older painkiller that is sold over the counter as Aleve. But the report provided relatively few details.

“We talked internally. Should some action be taken? We did not feel we had sufficient evidence to act on it,” Curfman says.

But on Nov. 21, 2005, Curfman was deposed in Boston by lawyers from the firm of Lieff Cabraser Heimann and Bernstein, who represent plaintiffs in one of the Vioxx suits. During the deposition, which also included attorneys for the drugmaker, they showed Curfman an internal Merck document dated July 5, 2000—after the VIGOR manuscript was submitted to the journal, but well before the study went to press.

It indicated that two Merck authors on the VIGOR study knew of three additional heart attacks among Vioxx patients in the study, which had not been disclosed to The New England Journal of Medicine. The heart attacks occurred in the final five weeks of the trial and in patients at low risk for heart problems.

The plaintiff’s lawyers also showed him early versions of the manuscript containing the original version of the deleted table, he says. This version also revealed more cardiovascular problems potentially connected to Vioxx than those had been discussed in the published study.

Curfman says the editors had assumed that the VIGOR manuscript only included limited data on heart attacks because that was all that was available at the time. “It turns out that they had quite a bit more already worked up,” he says. He raced back to the office and spent the next few weeks analyzing all the VIGOR drafts, raw data and correspondence.

At 3:00 P.M. today, Curfman and two other editors released an editorial on The New England Journal’s Web site entitled “Expression of Concern,” which calls on the VIGOR authors to submit a correction of the 2000 manuscript. “Taken together, these inaccuracies and deletions call into question the integrity of the data on adverse cardiovascular events in this article,” it read.

Curfman says he called lead author Claire Bombardier of the University of Toronto, on Monday, indicating that the statement would be published. She told him that she would begin working on a correction. However, in an e-mail to Forbes.com, Bombardier said that the VIGOR paper appropriately disclosed the data and that the authors were working on finalizing a response to the editorial.

Catharine Whiteside, dean of medicine at the University of Toronto, said today that she has yet to talk to Dr. Bombardier. “In the event that information is brought to light in which we would need to investigate Dr. Bombardier, we would initiate due process,” Whiteside says.

Hints that Vioxx might cause heart attacks had existed for years, as basic research pointed to a mechanism by which the drug might cause more clots. When VIGOR was published in The New England Journal of Medicine, there were already questions among scientists about the potential of Vioxx and related drugs made by Pfizer (nyse: PFE – news – people ) to cause heart attacks. Later on, the data about the VIGOR manuscript led researchers at the Cleveland Clinic to sound the alarm about Vioxx’s heart risk.

Some analysts have estimated Merck’s potential liability in the tens of billions of dollars. Others say that the risk to the drugmaker, once the most esteemed name in the pharmaceutical business, is impossible to know. The news that the once-popular arthritis drug may have caused thousands of heart attacks led to a firestorm about drug safety.

In a statement, Merck disputed The New England Journal analysis. “The VIGOR publication, which was peer-reviewed, fairly and accurately described the results of the study as of the prespecified cutoff for analysis. The additional events referred to in the editorial were events that were reported after the prespecified cutoff date and, therefore, these were not included in the primary analysis reported in the article.

“Nevertheless, the additional events were disclosed to the FDA in 2000, presented publicly to the FDA’s Advisory Committee in February 2001 and included in numerous press releases subsequently issued by Merck. We also note that these additional events did not materially change any of the conclusions in the article.”

Curfman responded, “We’re not buying into that.”

 

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Cases of wilful misrepresentation are a rarity in medical advertising. For every advertisement in which nonexistent doctors are called on to testify or deliberately irrelevant references are bunched up in [fine print], you will find a hundred or more whose greatest offenses are unquestioning enthusiasm and the skill to communicate it.

The best defence the physician can muster against this kind of advertising is a healthy skepticism and a willingness, not always apparent in the past, to do his homework. He must cultivate a flair for spotting the logical loophole, the invalid clinical trial, the unreliable or meaningless testimonial, the unneeded improvement and the unlikely claim. Above all, he must develop greater resistance to the lure of the fashionable and the new.
- Pierre R. Garai (advertising executive) 1963