Los Angeles, CA- The diabetes drug Avandia, made by GlaxoSmithKline, hit the news with a bang Jun 14, 2007, when the influential New England Journal of Medicine published a study by heart expert Dr. Steven E. Nissen showing that patients taking the drug had a 43% increase in heart attack risk.
This worrying news caught the FDA, diabetics and doctors by surprise and caused a panic reaction including an immediate drop in prescriptions for Avandia (and sales for GlaxoSmithKline), a Senate committee hearing, an FDA investigation and new analysis. It led to a war of words between the supporters of Avandia, and the critics of the drug, its manufacturer and the FDA.
There is good reason for a diabetic person to be afraid after learning that the drug he or she takes carries with it a whopping increase in heart attack risk. Diabetics are at increased risk for heart attack and stroke to start with, and any increase in that risk is serious.
The most important consequences of the Nissen report were that the FDA almost immediately required a Black Box (highest level) warning on Avandia's packaging warning of the increased heart attack risk, and doctors around the world decided not to take any chances and backed off on any new prescriptions of the drug. They likely concluded "why risk any danger to my patient's well-being, and why risk a law suit?"
On August 7 the Annals of Internal Medicine published a new report online on the Avandia risks by Dr. Sanjay Kaul, a cardiologist and professor of medicine at the University of California, Los Angeles. He and his colleagues say they re-examined the same trials that Nissen had used in his study, and found that the Nissen study had excluded certain trials that should have been included, trials that would have lowered the risk calculations because in those studies no heart attacks occurred.
Dr. Kaul concluded that none of these clinical trials had been designed to look at heart attack risk in long-term use of Avandia, and that therefore the true increased risk of heart attack connected with Avandia is not yet known. The FDA's advisory committee last week recommended that Avandia stay on the shelves, available for prescription, but with the warning included. Nissen defends his study, pointing out that the FDA's recent analysis mirrors his own conclusions.
It is confusing and troubling to have experts weighing in on both sides–troubling because it is hard to find a scientist or researcher without some monetary conflict of interest. Lawmakers in Congress are now talking about making the FDA bar anyone with a conflict of interest from the powerful outside advisory panels the FDA relies on. The FDA has said it only intends to bar advisors with financial ties to drug and medical device companies that exceed $50,000, which seems a relatively high cut-off line. Insiders say the FDA tends to pack panels with clinicians more apt to keep questionable products on the market to help their patients, and includes fewer drug safety proponents who argue for restrictions and market withdrawals.
The drug industry spends billions of dollars in the United States each year to support and fund universities, researchers and major hospitals. The drug industry's long arm reaches out to many of the leading experts in the various fields of health. The FDA has said it has a difficult time finding enough scientists free of conflicts to establish the advisory panels it needs.
Last week, of the 26 members of the panel that recommended keeping Avandia on the market, five had direct financial ties to GlaxoSmithKline, or to rival manufacturers. One of those, Dr. John R.Teerlink, director of the heart-failure clinic at the San Francisco Veterans Affairs Medical Center, reported receiving funding in the highest category-between $10,001 and $50,000 from a drug company that competes with Glaxo. He agreed that the heart attack risks now associated with Avandia are real, but he voted with the majority to keep the drug on the market.
By now, however, it may be too late for Avandia. Likely every diabetic in the U.S., every pharmacist, and every doctor treating diabetics has the words "Avandia linked to increased heart attack risk" burned into memory. Anyone who has taken Avandia in the past or continues to take it is going to point the finger of blame at GlaxoSmithKline in the event of heart failure. All these studies and "reassurances" won't stop the lawsuits that will follow.