Journal releases Vioxx study
LONDON, England (AP) -- A
medical journal published a study Tuesday of coronary disease related
to the anti-inflammatory drug Vioxx after withholding the report
because the researcher said he had been threatened by superiors at the
U.S. Food and Drug Administration.
The Lancet, which originally planned to publish the
paper on November 17, released the study online.
Dr. David Graham, who works in the FDA's office of drug
safety, has said he was firmly discouraged from publishing his data
questioning the safety of Vioxx, which was withdrawn from the market in
September.
"I was
sent an e-mail by one of my supervisors threatening me with severe
consequences" if the paper was published, Graham said in a
telephone interview Monday. Believing he was threatened with dismissal,
he said he asked the Lancet to withdraw the paper from publication in
November.
The FDA agreed earlier this month that the study could
be published. Graham's conclusion that the drug was responsible for
between 88,000 and 140,000 excess cases of serious coronary heart
disease had previously been disclosed.
Kathleen Quinn, a spokesman for the FDA in Washington,
said the agency had no comment on the Lancet's publication of Graham's
report.
Dr. Steven Galson, acting director of the FDA's Center
for Drug Evaluation and Research, had contacted the Lancet before the
originally proposed publication date, raising questions about the paper.
"Some of the questions involve basic data integrity.
(Graham) has declined to address these issues, and we think it's
important that your readers know this," Galson said in an e-mail to
Lancet editor Richard Horton.
The manufacturer, Merck & Co., is now defending at
least 700 lawsuits in the United States related to the drug. The
company withdrew it from sale in September after a study concluded that
it doubled a patient's risk of heart attacks and strokes.
The study by Graham and colleagues published by the
Lancet compared the incidence of coronary heart disease in patients
taking Vioxx and similar drugs known as cox-2 inhibitors.
Graham's team analyzed data from 1.4 million people in
California who had used those and similar drugs from 1999 to September
2004.
They
concluded that those taking Vioxx had a 34 percent higher chance of
coronary heart disease when compared with other drugs.
"An
estimated 88,000-140,000 excess cases of serious coronary heart disease
probably occurred in the U.S.A. over the market life of rofecoxib,"
Graham said, using the generic name of Vioxx.
"The U.S. national estimate of the case-fatality rate
(fatal acute myocardial infarction plus sudden cardiac death) was 44
percent, which suggests that many of the excess cases attributable to
rofecoxib use were fatal."
In a commentary published by the Lancet, Simon R.J.
Maxwell and David J. Webb of the University of Edinburgh in Britain
said that researchers should now look at other similar drugs.
Pfizer Inc. also announced that a study of its pain drug
Celebrex showed it had similar problems at high doses.
"It now falls to the manufacturers, under the careful
review of the regulatory authorities, to provide all the evidence that
this class of drugs is safe, if necessary including studies that
directly address cardiovascular morbidity as a primary outcome," Webb
wrote.
Copyright 2005 The
Associated Press. All rights
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