Avandia study results leaked to drug maker

Weeks before a damaging report on the diabetes drug Avandia (rosiglitazone) was to appear in The New England Journal of Medicine, a peer reviewer for the journal broke confidentiality rules by sending a copy of the results to an employee of the drug’s manufacturer, a report released Wednesday in Nature indicates.

On May 21, 2007, NEJM published on its web site the results of a study review showing that Avandia increased the risk of heart attack by 43 percent in patients who took the drug for 2 years or longer. The report gained widespread media attention, prompted the Food and Drug Administration to issue a safety warning, and led to a 13-percent drop in the stock price of GlaxoSmithKline (GSK), the drug’s manufacturer.

Earlier in May, reviewer Steven Haffner, a diabetes researcher with the University of Texas Health Science Center at San Antonio, sent a copy of the upcoming NEJM article to Alexander Cobitz, a GSK employee whom Haffner had known from working on a prior Avandia trial.

“Why I sent it is a mystery,” Haffner told Nature. “I don’t really understand it. I wasn’t feeling well. It was bad judgment.”

According to Haffner, Cobitz never asked to see the draft. Nancy Pekarek, a GSK spokeswoman, said that the company offered no input to Haffner on the study review. She also reported having no knowledge of anyone at GSK informing NEJM about the leak.

In addition to his involvement on the steering committee of a GSK-sponsored clinical trial of Avandia, Haffner told Nature that he had given many talks for the company, although he declined to state how much he had been paid.

He emphasized that the release of the study review findings to GSK was not financially motivated: “I’ve got a considerable amount of money. I didn’t do it to raise my income or anything like that.”

When the NEJM report came out, GSK contested the methodology of the study review and “strongly disagreed” with the conclusions.

On June 5, GSK-sponsored investigators published their own report in NEJM online documenting the interim results of the company’s RECORD trial, a study launched in 2001 to monitor adverse cardiac events with Avandia. This report mentioned the study review published in May, but went on to conclude that the new data from RECORD “were insufficient” to link Avandia with an elevated risk of heart attack.

According to Pekarek, GSK’s inside knowledge of the study review results caused a sense of urgency to swiftly publishing the RECORD data, which the FDA had previously asked to see.

NEJM spokeswoman Karen Pederson told Nature that while the journal does not discuss specific peer reviewers, their policy is to ban any reviewer who breaks confidentiality from future reviewing and from submitting editorials.

In November, GSK added a black-box warning on Avandia package to comply with orders by the FDA. While the warning is extensive and includes the study review findings, it also mentions that “the available data on the risk of myocardial ischemia are inconclusive.”

SOURCE: Nature, January 31, 2008.