According to a November 2007 report by the Senate Finance Committee, an analysis by FDA scientists presented at a July 30, 2007, safety panel meeting estimates that Avandia has caused approximately 83,000 excess heart attacks since coming on the market.
The report entitled, "The Intimidation of Dr. John Buse and the Diabetes Drug Avandia," summarizes the Committee's findings regarding GlaxoSmithKline's intimidation of Dr Buse, an independent scientist who first voiced concerns about Avandia back in 1999.
The Committee points out that Dr Buse is an expert in diabetes with extensive research experience in the thiazolidinedione class of drugs that includes Avandia and states: "Corporate intimidation, the silencing of scientific dissent, and the suppression of scientific views threaten both the public well-being and the financial health of the federal government, which pays for health care."
In November 2007, the FDA added a black box warning to GlaxoSmithKline's diabetes drugs Avandia, Avandamet, and Avandaryl about an increased risk of heart attacks, and a boxed warning about an increased risk of heart failure was added in August 2007.
On October 26, 2007, Senator Chuck Grassley (R-Iowa), ranking member of the Finance Committee, sent a letter to FDA Commissioner Andrew von Eschenbach asking him to respond to reports that on October 2, 2007, the agency convened a drug safety oversight board that voted to keep Avandia on the market by a one-vote margin while considering whether to add a second warning.
"The Avandia case continues to present new rounds of questions about the way the FDA monitors and assesses drug risks and decides whether to let the public know about emerging risks," Senator Grassley said in a press release the same day.
The Senator also asked the Commissioner to explain the conditions governing disclosure of this information. "I have yet to see any public notification of this vote," he states.
"Accordingly," he writes, "I would appreciate information from the FDA regarding the internal policies and procedures governing the DSOB and the terms and conditions governing the release of information from the DSOB to the public."
The Department of Veterans Affairs was among those who voted to remove Avandia from the market and has since removed Avandia from its formulary of approved drugs. On December 6, 2007, two pharmacy benefit managers, Prime Therapeutics and HealthTrans followed suit and announced the removal of Avandia from their formularies.
The studies verifying the dangers of Avandia have been non-stop over the past 6 months. On June 5, 2007, the New England Journal of Medicine published a paper by Dr Jeffrey Drazen, Dr Stephen Morrissey and Dr Gregory Curfman, which drew more attention to the safety concerns that were first reported in a study in the NEJM by Cleveland Clinic cardiologist Dr Steven Nissen and Kathy Wolski, in May 2007.
The paper cites an analysis which showed about a 40% increased risk of myocardial infarction in patients receiving Avandia when compared to patients receiving diabetes drugs such as metformin or a sulfonylurea or a placebo.
On September 11, 2007, the Journal of the American Medical Association published two more studies. The first, co-authored by Dr A Michael Lincoff and Dr Nissen, found Avandia's main competitor, Actos, appeared to protect diabetic patients from heart attacks, stroke and death by 18%. The second, by Dr Sonal Singh and researchers at Wake Forest University, concluded that Avandia increased heart attack risks by 42%.
On December 12, 2007, JAMA reported another population-based study by Canadian researchers of patients 66 and older with diabetes, that found thiazolidinedione treatment, primarily with Avandia, was associated with an increased risk of congestive heart failure, acute myocardial infarction, and mortality when compared with other combination oral hypoglycemic agent treatments.
According to the Senate Committee report, if GSK had considered Avandia's increased cardiovascular risk more seriously when the issue was first raised in 1999 by Dr Buse, "instead of trying to smother an independent medical opinion," some of the 83,000 heart attacks may have been avoided.
The report says the Committee found it "most troubling" that plans to silence Dr Buse involved discussions by GSK executives at the highest levels, including then and current, CEO Jean-Pierre Garnier.
In response to a letter dated May 21, 2007, in which the Committee asked about the retaliation against Dr Buse, the report notes that GSK issued a press release to refute the allegations and the Wall Street Journal reported that, "[GSK] called the suggestion 'absolutely false.'"
