Merck's Deleted Data

[Tara]

Merck's Deleted Data

Robert Langreth and Matthew Herper

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."
_________________
Health Wishes

Tara