The panel’s votes, taken after two days of intensive scientific discussions, were a blow to GlaxoSmithKline, which makes Avandia. The company argued that Avandia is a safe and needed option in treating diabetes.  But panel members voiced great skepticism about the company’s trustworthiness after questions were raised about its clinical trials. And internal company documents showed that the company for years kept crucial safety information about Avandia from the public.  The panel took six votes on a variety of issues, but its most important came near the end of the meeting when asked what the Food and Drug Administration should do. Of the panel’s 33 members, 12 voted that Avandia should be withdrawn; 10 voted that its sales should be restricted and the warnings on its label enhanced; 7 voted only to support enhanced warnings on the drug’s label; and 3 voted that the drug should continue to be sold with its present warnings unchanged. One member abstained, and no one voted for a final option, to weaken the label’s present heart warnings.  Dr. Janet Woodcock, director of the drug center at the F.D.A., said that the agency took the panel’s advice seriously and that it would consider its regulatory options.  The F.D.A. often takes the advice of its advisory panels, but in this case it was hard to predict what the agency would do, given the split nature of the vote. The agency allowed competing visions to spill out in the advisory hearing — something unheard of just a few years ago, when the F.D.A. nearly always spoke with a single voice.  “We will come to a decision as soon as possible, and we will announce that publicly,” Dr. Woodcock said.  Approved in 1999, Avandia helps control blood sugar levels in diabetics by making patients more sensitive to their own insulin. It is one of a class of three drugs, the first of which, Rezulin, was withdrawn because it caused liver damage. The other drug in the class, Actos, made by Takeda, has appeared safe.  Avandia, which was once the biggest-selling diabetes medicine in the world, saw its sales abruptly decline in 2007 after a study by Dr. Steven Nissen, a Cleveland Clinic cardiologist, found that it increased the risk of heart attacks. An advisory committee in 2007 decided that Avandia did increase heart risks but voted to keep it on the market.  Many of the same experts who decided to keep the drug on the market in 2007 voted Wednesday that it should be withdrawn or restricted. Those restrictions could mean that patients would have to apply for special permission to use the drug.  Reactions were as mixed as the vote.  In a statement shortly after the committee adjourned, GlaxoSmithKline noted that a majority of committee members had voted to keep Avandia on the market.  Dr. Nissen said the committee’s vote was the best he could hope for. “Effectively, this drug is gone,” he said.  Dr. Sanjay Kaul, who voted to require stronger warnings, said that the F.D.A. must ensure that Avandia was used far less regularly. “Make sure this is available as second-line and not as first-line,” Dr. Kaul urged.  The F.D.A. generally undertakes programs to restrict a drug’s sales only when a drug offers a unique benefit, something no study has shown about Avandia. Among the examples of drugs the F.D.A. has restricted are Accutane, an acne drug that can cause birth defects, and Lotronex, a drug for irritable bowel disease that in rare instances is fatal. A majority of the committee found that Avandia increased the risk of heart attacks but a majority also said that studies had failed to prove it increased the risk of death. A majority also decided that if Avandia were to continue to be sold, the company should complete a clinical trial to prove it was safe. But several members said that the vote probably made a trial impossible because patients would not want to risk taking Avandia.  GlaxoSmithKline said it was in the midst of a clinical trial that would test definitively if Avandia caused heart attacks. Several panel members said the trial came too late.  “The best time to do the trial would have been when the first signal about lipids came up way back in the 1990s,” said Dr. Peter J. Savage, a member from the National Institute of Diabetes, Digestive and Kidney Diseases.  In the 1990s, GlaxoSmithKline decided against just such a study because it feared that the results might hurt sales, according to internal company documents.  Throughout the meeting, GlaxoSmithKline was criticized over repeated findings by federal officials that the company had failed to conduct its Avandia studies appropriately.  At one point, Dr. Murray Stewart, a vice president at GlaxoSmithKline, was given five minutes to explain why a crucial trial called Record was done properly.  But he was immediately followed by Dr. Thomas A. Marciniak, a team leader at the F.D.A., who found numerous mistakes in the study that served to hide Avandia’s risks.  Time and again, GlaxoSmithKline overruled doctors who had concluded that patients had been harmed by Avandia, Dr. Marciniak said.  Dr. Stewart tried to respond, but the committee’s chairman silenced him.  Dr. William Knowler, a panel member who is chief of diabetes epidemiology at the National institute of Diabetes and Digestives and Kidney Diseases, described a different study done by GlaxoSmithKline as “totally incorrect and deceptive.”  Dr. David Capuzzi, a panel member who treats diabetics, said that clinicians need as many choices of drugs as possible, and he voted to keep Avandia on the market with no new restrictions.  Chuck Keyserling, a diabetes patient, echoed those concerns during a brief public part of the meeting. He said that he had been taking Avandia for 10 years.  “Please think about those of us who have flourished on Avandia,” Mr. Keyserling told the panel. “For those people, a negative position on Avandia may be a death sentence.”  Dr. John Teerlink, a panel member who voted Wednesday to restrict the drug, said he had served on the advisory panel in 2007 that voted to continue to allow Avandia to be marketed. But he said he made the earlier vote with the understanding that GlaxoSmithKline would use the added time to prove that its drug was safe and that he had not been convinced.
The majority of panel members voted either to withdraw the diabetes drug Avandia or allow sales with controls.