Three years ago, Dr.Nissen, a cardiologist at the Cleveland Clinic, conducted a landmark study that suggested that the best-selling diabetes drug Avandia raised the risk of heart attacks. The study led to a Congressional inquiry, stringent safety warnings, a sharp drop in the drug’s sales of GlaxoSmithKline, Avandia’s maker.
The battle between Dr. Nissen and GlaxoSmithKline was waged from afar in news releases and published papers. But on May 10, 2007, 11 days before Dr. Nissen’s study was published in The New England Journal of Medicine, he and four company executives met face to face in a private meeting whose details have not been disclosed until now.
Fearing he would face pressure and criticism from executives, Dr. Nissen secretly recorded the meeting — which is legal in Ohio as long as one party to the conversation is aware of the taping.
What was said at the 2007 meeting raises questions about science and ethics that have suddenly become keenly relevant. A Congressional investigation concluded that GlaxoSmithKline had threatened scientists who tried to point out Avandia’s risks, and internal memorandums from the Food and Drug Administration show that some government health officials want Avandia withdrawn. The drug is still being taken by hundreds of thousands of patients.
So the battle over Avandia has begun anew, and issues raised in the meeting between the four executives and Dr. Nissen are likely to be raised again. For instance, during the meeting, company executives repeatedly promised to begin a crucial analysis of the safety of Avandia “within days.” Nearly three years later, such a study has not been published in a medical journal, although the company has posted results on its Web site.
Also during the meeting, Dr. Krall, GlaxoSmithKline’s chief medical officer, predicted almost exactly the results of another crucial study of Avandia that was two months from publication and whose results, according to scientific protocols and the company itself, should have been kept secret from the company. In an interview, Dr. Nissen said the recording showed that the executives hoped to persuade him not to publish his study by suggesting that they had contradictory information they would share with him in a joint study.
“In retrospect, it seems clear that neither statement was true,” Dr. Nissen said. “They did not have contradictory data, and they never intended to cooperate in any analyses.”
In response to questions, GlaxoSmithKline said that its executives went to see Dr. Nissen to discuss a possible research collaboration and to review the safety information surrounding Avandia.
The recording and events surrounding it offer a rare window into an unusual confrontation between a prominent cardiologist and one of the world’s biggest drug makers. Since industry is the source for much of the money and studies available in academic medicine, executives normally drive the agenda in such meetings.
But GlaxoSmithKline was sued in 2004 by Eliot Spitzer, who was New York’s attorney general at the time, over the company’s failure to publicize studies that helped to reveal that antidepressants could lead children and teenagers to engage in suicidal behavior. The company settled the lawsuit by agreeing to post all of its clinical trial data. These Internet postings became the grist for Dr. Nissen’s analysis.
During the meeting with Dr Nissen, the four executives spoke as if they did not know the results of Dr. Nissen’s still-unpublished study. And Dr. Nissen did not mention that he had already sent it to the journal, the recording shows.
But a week before the meeting, the Congressional investigators said, GlaxoSmithKline had been secretly and inappropriately faxed a copy of Dr. Nissen’s manuscript by a journal reviewer who also worked as a consultant to GlaxoSmithKline.
The company confirmed that the faxed copy of Dr. Nissen’s study had been read by its executives, “some of whom attended the meeting with Dr. Nissen.” At one point, the executives said that studies showed that Avandia had no impact on cardiac death rates. Dr. Nissen’s study had concluded that the risk was increased by 64 percent.
At another point, Nevine Zariffa, a company statistician, asked what Dr. Nissen was studying. “So you’ve done a summary type meta-analysis looking at” heart attacks and heart-related deaths? she asked, precisely describing Dr. Nissen’s study.
“That’s right,” Dr. Nissen answered, then asked rhetorically, “Now, what am I going to do? What is my responsibility? I mean, answer the question for me. Do I sit on it? Drug’s being used by how many people?”
Dr. Nissen lost patience regarding the increased risk of heart attacks, or myocardial ischemia, in Avandia patients. “I hope you guys understand how much trouble G.S.K. is in here,” he said. “You’ve got a bunch of people who are incredibly vulnerable to myocardial ischemia, and you’ve had evidence that you’re provoking ischemia in those people, and that is of grave public health consequences.”
Dr. Krall asked Dr. Nissen if his opinion of Avandia would change if the Record trial — a large study then under way to assess Avandia’s risks to the heart — showed little risk. Dr. Krall said he did not know the results of Record.
“Let’s suppose Record was done tomorrow and the hazard ratio was 1.12. What does…?” Dr. Krall said.
“I’d pull the drug,” Dr. Nissen answered quickly.
The interim results of Record were hastily published in The New England Journal of Medicine two months later and showed that patients given Avandia experienced 11 percent more heart problems than those given other treatments, for a hazard ratio of 1.11. But the trial was so poorly designed and conducted that investigators could not rule out the possibility that the differences between the groups were a result of chance.
Even as Dr. Krall and the other executives tried to corral Dr. Nissen, executives were strategizing over how to blunt the impact of his study if it were published. But according to internal documents, the company’s own scientists had concluded that Dr. Nissen’s work was sound.
In one internal e-mail message, the Congressional investigation found that a company statistician stated that “there is no statistical reason for disregarding the findings” of Dr. Nissen’s study. In another, Dr. Moncef Slaoui, head of research at GlaxoSmithKline, wrote that federal drug regulators, Dr. Nissen and the company’s own researchers all seemed to agree that studies of the drug showed that it substantially increased the risks of death and heart attacks, also known as ischemic events:
“F.D.A., Nissen and G.S.K. all come to comparable conclusions regarding increased risk for ischemic events, ranging from 30 percent to 43 percent!” Dr. Slaoui wrote.
In public comments after Dr. Nissen’s study was published, company executives insisted that the study had been “based on incomplete evidence and a methodology that the author admits has significant limitations.”
If you or a family member has been personally injured because of the fault of someone else: by the use of dangerous and defective drugs, bad products, or toxic injury etc then please contact the Dallas Texas Avandia Defective Drug Attorney Dr. Shezad Malik. For a no obligation, free case analysis, please call 888-210-9693 or Contact Me Online.
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