On September 23, 2010, the U.S. Food and Drug Administration (FDA) placed significant restrictions on the anti-diabetic drug Avandia. The FDA analyzed multiple studies and concluded that use of rosiglitazone (the active ingredient in Avandia) appeared related to increased risk of cardiovascular problems, particularly heart attacks and strokes. The restrictions require all physicians to prescribe Avandia only as a last resort after all other medications and treatments for Type 2 diabetes have been tried.
Problems with Avandia started appearing in 2007 when a Cleveland clinic determined that Avandia use led to an increase in the chance of heart attacks by 43 percent. This prompted the FDA to place a “black box” Avandia warning on the product, requiring the label to explain the side effects the drug causes. Apparently, FDA officials could not be convinced to remove the drug from the market altogether, so no Avandia recall is in effect. Meanwhile, evidence of the drug’s problems has continued to grow. For instance, in the same year, the New York Times reported that in 2000 a diabetes expert had warned the FDA that Avandia contributed to heart problems; the FDA reprimanded GlaxoSmithKline.
By 2010 the situation worsened: A U.S. Senate committee had found that GlaskoSmithKline knew about Avandia’s risks yet declined to inform the public. Calls to remove the drug from the market grew. Then, the New York Times discovered that one of GlaxoSmithKline’s predecessors, SmithKline Beecham, had found that Avandia was not only no better than a competing drug, Actos, but it also caused heart problems in users. The pharmaceutical company had buried the report because it had no other promising drugs in development at the time. A SmithKline executive in a March 29, 2001, memo wrote:
Per Sr. Mgmt request, these data should not see the light of day to anyone outside GSK.
Meanwhile, Dr. David Graham of the FDA conducted a separate study comparing Avandia to Actos. Using data from 227,500 patients, he found that Avandia users were more likely to suffer strokes or heart failure and were more likely to die than Actos users. Dr. Graham advocated removing Avandia from the market in early 2010.
The FDA decided to convene a panel in June 2010 to discuss whether to remove Avandia from the market. Prior to the meeting, it published a report heavily criticizing a 2009 study (“RECORD”) by GlaxoSmithKline that had attempted to clarify concerns about the drug’s cardiovascular effects. Over a 5.5 year period, RECORD evaluated 4,500 individuals, some on Avandia, the rest on other diabetes drugs, and it found no increased heart problems in Avandia users. The FDA argued that GlaxoSmithKline had used an inadequate methodology in the study and had drawn the wrong conclusions from the evidence. Indeed, the FDA even discovered that Avandia patients who suffered heart problems were not counted against the drug’s effectiveness. As a result, the FDA ordered GlaxoSmithKline to readjudicate its RECORD conclusions.
The panel ultimately decided not to recommend removing Avandia from the market. Instead it severely restricted its use, so a person with Type 2 diabetes had to try every other prescription medication before turning to Avandia. The European Medicines Agency, on the other hand, has removed Avandia from its markets altogether.
On November 25, 2013, the FDA removed the restrictions on Avandia. The independent readjudication of the RECORD data showed that Avandia was no more likely to cause heart attacks than standard-of-care diabetes drugs metformin and sulfonylurea. However the readjudication did not compare the probability that Avandia would cause a heart attack to a placebo because placebos weren’t part of the RECORD trial.
Thousands of Avandia-related lawsuits have been filed against GlaxoSmithKline to date, but the Rottenstein Law Group does not know of any Avandia class action lawsuits. In February 2012, GlaxoSmithKline announced an Avandia settlement with 20,000 litigants, according to Bloomberg. It settled 15,000 claims in 2011 for $700 million, and the reported average amount of compensation in each Avandia settlements was roughly $50,000. No Avandia jury trials have taken place.