Was the FDA Negligent in Overseeing the Diabetes Drug, Avandia®?
WASHINGTON, DC -- June 22, 2007 --The Food and Drug Administration (FDA) may have been too hasty in approving the diabetes drug, Avandia®, and negligent in issuing timely warnings about its safety, according to some participants at a recent hearing before the House Oversight and Government Reform Committee. The hearing was called after a negative report about Avandia® was published in the New England Journal of Medicine. A meta-analysis of 42 studies, the article said that compared to patients who took fake pills or placebos, diabetics using Avandia® were 43 percent more likely to have heart attacks (N Engl J Med., 2007 Jun 14; 356(24): 2457-71).
The FDA approved Avandia® (rosiglitazone) in 1999 to lower blood sugar levels in patients with type 2 diabetes, a disease that affects over 17 million Americans. When deciding whether or not Avandia® sales should go forward, an FDA medical reviewer warned that the drug may have a "deleterious long-term effect on the heart" and recommended a post-marketing study to investigate this problem.
The FDA and Avandia®'s manufacturer, SmithKline Beecham (now GlaxoSmithKline), agreed on a post-market study, which became known as ADOPT. However, its purpose was to consider Avandia®'s ability for long-term control of blood sugar levels, not whether it increased heart attack risks. "Doctors and their patients should be able to turn to FDA for guidance about the safety of the drugs they take. But in the case of Avandia, FDA did not insist upon the data it needs to answer their questions definitively," commented Rep. Henry Waxman (D-CA), the Committee chairman.
Dr. John Buse, a director of the Diabetes Care Center at the University of North Carolina School of Medicine, worked on projects for SmithKline Beecham and other drug companies for many years. In March 2000, he sent letters to the FDA and SmithKline Beecham, warning about Avandia®'s potential for heart problems and requesting further studies. In his letter to the FDA, Dr. Buse encouraged cardiovascular safety trials of Avandia® in high-risk populations and accused SmithKline Beecham of overstating the safety of Avandia®. At the House Committee hearing, Dr. Buse testified that SmithKline Beecham had tried to pressure him into keeping quiet about Avandia® safety issues. According to Dr. Buse, the company had called his criticisms "scurrilous," implied that his actions could result in drops in the drug company's stock price and said that he was a liar.
On May 23, 2007, the FDA finally requested that a "black box" warning be added to the prescribing instructions for Avandia®. Such a warning is the strongest alert that can be given for a drug, short of taking it off the market. In this case, however, the warning was about the increased risk of congestive heart failure rather about heart attack risks.