January 31, 2008
Researcher Leaked Critical Data to Drug Maker
Iowa Senator Charles Grassley said yesterday that Dr. Steven M. Haffner, a well-known diabetes expert at the University of Health Science Center in San Antonio, had leaked confidential, unpublished information to GlaxoSmithKline (GSK) that questioned the safety of the company's diabetes drug Avandia.
A New York Times report said that Dr. Haffner had faxed the document, a medical journal article he had agreed to read as part of the normal prepublication peer review process for The New England Journal of Medicine, to GSK last year. The article, a pooled analysis of Avandia studies, had been submitted for publication by Dr. Steven E. Nissen of the Cleveland Clinic. It was published in late May and suggested that the diabetes drug increased the risk of heart attack by more than 40 percent.
According to Senator Grassley's statement, "The most troubling aspect of this situation is that the integrity of another aspect of the scientific process is called into question "” scientific peer review." The peer-review process is meant to ensure "that other scientists will judge a study's quality before it is made public," the statement said.
Senator Grassley is the ranking Republican on the Senate Finance Committee, and has long been critical of the business relationships between doctors and pharmaceutical companies. Along with his statement, he released a copy of a letter he had submitted to GSK asking the company what action was taken after they received the article from Dr. Haffner.
An article published Wednesday in the online journal Nature quoted Dr. Haffner as saying, "Why I sent it is a mystery. I don't really understand it. I wasn't feeling well. It was bad judgment." Dr. Haffner did not respond to the NY Times' phone calls and e-mail messages seeking comment on Wednesday.
Senator Grassley said that Dr. Haffner had received $75,000 in consulting and speaking fees from GSK since 1999.
GSK spokeswoman Nancy Pekarek said Dr. Haffner sent the article to the company on May 3, more than two weeks before it was published in the journal.
He "expressed concerns and questions regarding the methodology of the analysis, and sent the article to GSK for advice from experienced statisticians," she said. But Ms. Pekarek said the company did not provide comments or any other information. "We believe GSK acted appropriately and responsibly in responding to the situation."
The New England Journal of Medicine (NEJM) prohibits disclosure of an article's contents prior to publication as a way of protecting exclusivity of its content and intellectual property rights of scientists submitting articles.
An NEJM spokeswoman said the journal was aware of the allegations against Dr. Haffner. "Any breach of ethics by a reviewer would be taken very seriously by the editors, but would be handled as a private matter," the Journal said in an e-mailed statement to the New York Times.
Dr. Jerry Avorn, a professor of medicine at Harvard Medical School, told the New York Times that in addition to violating the NEJM's rules, disclosure of a pending article would also be a breach of ethics. However he added he was not familiar with the specific allegations against Dr. Haffner.
A University of Texas Health Science Center statement issued Wednesday said they would investigate the matter. "Once the facts are understood, we will take swift and appropriate action," the statement said.
Dr. Nissen, the chief of cardiovascular medicine at the Cleveland Clinic, said Wednesday that he was disappointed in Dr. Haffner's decision to send the article to GSK.
"The integrity of the scientific review process is really very important in medicine," Dr. Nissen said. "The last thing I would have ever expected was that a respected reviewer for a prestigious journal would have, within hours of receiving a review, given it to a pharmaceutical company."
Dr. Nissen's article led the Food and Drug Administration (FDA) to order that a black"“box warning be placed on Avandia's label, driving down sales of the drug by more than half their 2006 levels of over $3 billion.
By receiving an early copy of the article, GSK could have used the time to mount a campaign to rebut the article's findings. Indeed, within days of the publication of Dr. Nissen's article, GSK began citing the interim results of another study, called Record that contradicted his findings.
But Ms. Pekarek said that even before receiving the Nissen article from Dr. Haffner the company had been weighing whether to look at preliminary results of the Record study, which at the time was still under way.
GSK's internal deliberations were based on the company's own findings of an increased heart attack risk from Avandia. The additional knowledge that an article critical of the drug's safety was soon to be published increased the urgency of looking at the interim Record results, she said.
Dr. Haffner, who had been involved in a clinical study that found Avandia worked better at controlling blood sugar than two other treatments, was quoted last year in the online medical publication TheHeart.org criticizing the publication of Dr. Nissen's study and of editorials that supported it in two other journals.
"The three major medical journals are becoming more like British tabloid newspapers. All they lack is a bare-chested woman on Page 3," Dr. Haffner was quoted as saying.
Dr. Nissen's full report was published in the May 21, 2007 edition of The New England Journal of Medicine. The full report can be viewed at http://content.nejm.org/cgi/reprint/356/24/2457.pdf.
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University of Health Science Center
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