> http://www.***.com/
> Missing Data on Celebrex
> Full Study Altered Picture of Drug

> By Susan Okie
> Washington Post Staff Writer
> Sunday, August 5, 2001; Page A11

> When editors of the Journal of the American Medical Association sent medical
> expert M. Michael Wolfe an unpublished study on the blockbuster arthritis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 cooking.net">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.

> Steven Geis, a vice president for clinical research of Pharmacia and one of
> the authors, said that only the first six months of data were presented
> because, after that, more patients withdrew from the comparison groups than
> from the Celebrex group, biasing later findings. He said a three-member
> executive committee, composed of authors who were not Pharmacia employees,
> approved the decision.

> "The intention really was not to be deceptive in any way," he said. "People
> thought that six months was the appropriate analysis."

> With inclusion of the later data, "the actual difference between Celebrex
> and [the other {*filter*}] are not as wide as they were at six months," he
> acknowledged. "But I think in the end, it does show that Celebrex has a
> superior safety profile."

> After reviewing the full study, the FDA's arthritis advisory committee
> concluded that Celebrex offers no proven safety advantage over the two older
> {*filter*} 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
> the 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."

> ? 2001 The Washington Post Company

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