By Rob Stein
Washington Post Staff Writer
Thursday, June 7, 2007
A prominent doctor who sounded an early alarm about a widely used diabetes drug testified yesterday that he was intimidated by the manufacturer when he raised concerns about the drug's safety.
John B. Buse of the University of North Carolina School of Medicine, the incoming president of the American Diabetes Association, told a congressional hearing that officials at SmithKline Beecham began pressuring him in 1999 after he questioned whether Avandia might cause heart problems.
Buse said company officials considered his actions "scurrilous" and implied that he might be held accountable for a $4 billion drop in the drug firm's stock.
"I was characterized as a liar and I was characterized as being for sale," Buse told the House Oversight and Government Reform Committee, which released a letter that he wrote in response.
"Please call off the dogs. I cannot remain civilized much longer under this kind of heat," Buse wrote.
Moncef Slaoui of GlaxoSmithKline, the company's new name after a merger, expressed regret about the episode, attributing it to the "passion" of officials at the time.
"I probably would not have done it the same way," Slaoui said. "We regret Dr. Buse felt pressured."
But Slaoui defended the drug's safety, saying numerous studies have shown no increased risk of heart attack.
"The overall safety of Avandia is comparable to other available oral anti-diabetes medicines," he said.
The revelations came during a tense four-hour hearing focused on how the Food and Drug Administration handled safety concerns about Avandia.
The drug, which has been used by 7 million people worldwide, including about 1 million Americans, was approved in 1999 to help patients with the most common form of diabetes control blood sugar levels. Doctors and patients taking the drug have been scrambling to decide what to do since the New England Journal of Medicine published an analysis on May 22 of 42 studies that concluded that Avandia increases the risk of heart attack by 43 percent.
Committee Chairman Henry A. Waxman (D-Calif.) criticized the FDA, saying it "dropped the ball" by not requiring the company to examine the drug's potential heart attack risks.
"Although Avandia has been on the market for eight years and has been used by millions of Americans, the post-market studies have not been done to say conclusively whether Avandia increases or decreases the risks of heart attacks. That's a major failure of our system," Waxman said.
FDA Commissioner Andrew C. von Eschenbach revealed that agency decided on May 23 to call for much stronger label warnings about the risks of congestive heart failure in patients taking Avandia and a similar drug called Actos.
But von Eschenbach said the agency is still analyzing conflicting data about whether Avandia increases the risk of heart attack.
"Up until this point in time we have not had sufficient data that we can rely upon to make a decision," he said.
The agency has scheduled a July 30 meeting of outside experts to evaluate Avandia and similar drugs, he said.
Yesterday's hearing was marked by tense exchanges between Waxman and several Republican committee members, who questioned whether the safety concerns and hearing were politically motivated.
"This does look like in fact it was a political concoction to go after a company, and I object to that," said Rep. Darrell Issa (R-Calif.), charging that the hearing was "politicizing science."
Issa and several other members aggressively questioned Steven E. Nissen of the Cleveland Clinic, whose analysis prompted the hearing, about why he contacted members of Congress before he contacted the FDA.
Nissen said he had approached several lawmakers in the hope that they would help him get access to data for his study.
"This is about patients, it's not about politics," Nissen said.
Waxman and other committee members said the episode provides support for legislation that would give the FDA more power to ensure drug safety.
"FDA needs the will, the resources and the authority to be a more effective watchdog of drug safety," he said.
Sen. Charles E. Grassley (R-Iowa), meanwhile, sent a letter to the FDA asking for an investigation into why an agency scientist was reprimanded for agreeing with a recommendation that stronger warnings were needed for Avandia.
"The Avandia case has opened a new round of questions about the way the FDA monitors drug risks and decides whether to let the public know about emerging risks," he said.