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By Susan Okie
When editors of the Journal of the American Medical Association
sent medical expert Dr. M. Michael Wolfe an unpublished study on
the blockbuster arthritis drug Celebrex last summer, he was impressed
by what he read.
Tested for six months in a company-sponsored study involving more
than 8,000 patients, the drug was associated with lower
rates of stomach and intestinal ulcers and their complications
than two older arthritis medicines -- diclofenac and ibuprofen.
JAMA's editors wanted to rush the findings
into print, and Wolfe and a colleague provided a cautiously favorable
editorial to accompany it. But in February, when Wolfe was shown
the complete data from the same study as a member of the Food and
Drug Administration's arthritis advisory committee, he said he saw
a different picture.
"We were flabbergasted," he said.
The study -- already completed at the time he wrote the editorial
-- had lasted a year, not six months as he had thought, Wolfe learned.
Almost all of the ulcer complications that occurred during the second
half of the study were in Celebrex users. When all of the data were
considered, most of Celebrex's apparent
safety advantage disappeared.
"I am furious. . . . I wrote the editorial. I looked like
a fool," said Wolfe, a Boston University gastroenterologist.
"But . . . all I had available to me was the data presented
in the article."
JAMA's editor, Catherine D. DeAngelis, said the journal's editors
were not informed about the missing data. "I am disheartened
to hear that they had those data at the time that they submitted
[the manuscript] to us," she said. "We are functioning
on a level of trust
that was, perhaps, broken."
The study's 16 authors included faculty members of eight medical
schools. All authors were either employees of Pharmacia, Celebrex's
manufacturer, or paid consultants of the company. For company-sponsored
studies, JAMA now requires a statement, signed by an author who
is not employed by the company, taking "responsibility for
the integrity of the data and the accuracy of the data analyses,"
DeAngelis added.
After reviewing the full study, the FDA's arthritis advisory committee
concluded that Celebrex offers
no proven safety advantage over the two
older drugs in reducing the risk of ulcer complications,
said FDA spokesman Susan Cruzan.
The company has requested a change in the drug's labeling to state
that it is indeed safer, but the FDA has asked for additional information
before making a decision.
Meanwhile, the JAMA article and editorial have likely contributed
to Celebrex's huge sales. "When the JAMA article comes out
and confirms the hype, that probably has more impact than our labeling
does," said Robert J. Temple, director of medical policy at
the FDA's Center for Drug Evaluation and Research.
James Wright, a professor of clinical pharmacology at the University
of British Columbia, said he complained to JAMA after noticing differences
between the published report and the data presented to the FDA.
He praised Public Citizen's
Health Research Group, a consumer organization, for filing a
lawsuit that led to the agency's putting all drug studies presented
to its advisory committees on its public Web site.
"Otherwise, we still wouldn't know this," Wright said.
"We would still be in the dark."
Washington Post, August 5, 2001;
Page A11
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