Merck Admits a Data Error on Vioxx
By ALEX BERENSON
Published: May 31, 2006
In an admission that could undermine one of its core defenses in Vioxx-related
lawsuits, Merck said yesterday that it had erred when it reported in early
2005 that a crucial statistical test showed that Vioxx caused heart problems
only after 18 months of continuous use.
That statistical analysis test does not support Merck's 18-month theory
about Vioxx, the company acknowledged yesterday.
But Dr. Peter S. Kim, Merck's chief scientist, said the company stood by the
overall findings it reported in 2005 — including the conclusion that the
drug's heart risks were not apparent if patients took it less than 18
But outside scientists said yesterday that Merck's admission, when
considered along with other clinical trials of the drug and studies tracking
real-world Vioxx use, supports critics' longstanding claims that Vioxx
caused heart problems quickly.
"There never was any evidence for the 18-month story," said Dr. Alastair J.
J. Wood, a drug safety expert at Vanderbilt University.
The 18-month issue is crucial both for the 20 million Americans who took
Vioxx, an arthritis drug and painkiller, and for Merck's future. Merck faces
at least 11,500 lawsuits, covering 23,000 people, from patients who say that
Vioxx caused their heart attacks and strokes. Merck cited the 18-month
theory when it withdrew Vioxx, a painkiller, from the market in September
2004, based on preliminary findings from a clinical trial called Approve.
In defending the lawsuits, Merck has consistently taken the position that
Vioxx can cause heart problems only if it is used continuously for more than
18 months. But in the five Vioxx court cases in which juries have reached
decisions so far, Merck has lost three times — twice in cases in which the
heart attack victim had taken the drug for fewer than 18 months.
Merck has based the 18-month theory largely on data from the Approve study,
in which the company tracked 2,600 patients in a test to see whether Vioxx
could prevent colon polyps.
In the Approve study, twice as many patients taking Vioxx suffered heart
attacks or strokes as those taking a placebo, or sugar pill. But most of the
difference appeared to occur after patients had taken Vioxx for 18 months in
a row, Merck has said.
When it reported the Approve results in The New England Journal of Medicine
early last year, Merck said that it had performed a statistical test to
examine whether Vioxx's risk changed over time. That test found with almost
total certainty that the drug had significantly higher risk than placebo
only after the 18-month benchmark — but no extra risk before that time.
Yesterday, Merck said it had made a mistake in reporting that result last
In reality, the test that the company said it had used to check the results
shows that there is a 7 percent chance that Vioxx has an equally high risk
of causing heart attacks both before and after the 18-month benchmark is
That 7 percent figure may seem like a relatively small chance of error, but
scientists say it is high enough to mean that Merck has not proved its
Critics had recently raised new questions about the Approve trial's results,
after the company submitted new data to the Food and Drug Administration as
part of a one-year follow-up study of patients in the trial.
Some outside scientists said that the new data indicated that Vioxx's
dangers became evident after only about four months of use. Merck disputed
that interpretation and said yesterday that its newly discovered mistake was
unrelated to that new data.
Dr. Kim said yesterday that Merck found its mistake only last week and
immediately told the F.D.A. and the non-Merck researchers who had taken part
in the Approve study, which was published in the March 17, 2005, issue of
The New England Journal of Medicine.
"We came forth quickly to let the study authors know about the error, let
the regulatory agencies know about the error," Dr. Kim said.
But Dr. Steven E. Nissen, the interim chairman of cardiovascular medicine at
the Cleveland Clinic, and a frequent critic of Merck, said the mistake the
company disclosed yesterday was yet another example of Merck's mishandling
data to make Vioxx seem safer.
"They're acknowledging that they misrepresented the Approve data, when they
reported that there was a statistically significant difference between the
first and the second 18 months," Dr. Nissen said. "There is no biologically
plausible reason to expect an 18-month delay. I never thought it made any
Dr. John Baron, a professor at the Dartmouth medical school and one of the
authors of the original journal article about Approve, said Merck's mistake
was relatively minor. In general, trying to calculate whether risks change
over time is very difficult, Dr. Baron said.
"The assessment of this constancy is something of an art. It's not a 'cut
and dry, it's there or it's not' business," he said.
"The evidence that the Vioxx effect begins immediately or quickly, or
however you want to describe it, is far from conclusive. The evidence that
it doesn't begin until 18 months is also not something that has been