David Graham and the Deathly Hallows

David Graham and the Deathly Hallows

He’s not a boy wizard, but he is surrounded by calculating adversaries and he does have an uncanny wizardry for exposing safety problems in drugs that have already been approved by his bureaucratic employers.

His name is Dr. David Graham, he’s a drug safety scientist, and he’s a rare ray of light in the dark hole known as the FDA.

Just another day at Hogwarts

Here’s a disturbing statistic: About 70 percent of all diabetes patients will eventually succumb to heart disease. So how would you describe a diabetes drug that increases cardiovascular risk?

One word: Unacceptable.

That was the word Dr. Graham used to describe Avandia when he appeared before an FDA panel last week.

In 2003, HSI first reported on an association between Avandia and an increased risk of congestive heart failure. More recently, in the e-Alert “Catching Up” (5/29/07), I told you about a New England Journal of Medicine study that reviewed more than 40 Avandia trials and found the drug to be linked to a significant increase in the risk of heart attack.

Dr. Graham told the Associated Press that keeping Avandia on the market “makes no medical sense and violated the principle taught us all in medical school, “First, do no harm.” He added: “A wrong decision will cost thousands of lives.”

So what was the panel’s decision? Panel members voted 22 to 1 to keep Avandia on the market. One caveat: The panel suggested that Avandia packaging carry “strict warnings.”

Just how strict will those warnings have to be to avoid the cost of thousands of lives?

Muggles abounding

After the decision was announced, Rebecca Killion (described in the New York Times as the panel’s patient representative) offered this simple insight: “My feeling here is that we’re being asked to take a very draconian action based on studies that are very inadequate for us to make that kind of decision.”

Heavens! Draconian! No, we certainly wouldn’t want to be too strict in our safety requirements for a drug that’s taken by millions of patients.

In the Times, Dr. Sidney Wolfe of Public Citizen pointed out that in addition to cardiovascular risks, Avandia has also been linked to liver problems and an increased risk of bone fracture. And he noted that if Avandia were up for approval today, the “draconian” FDA approval process would not give this drug the green light.

In short, the panel backed the wrong horse, even though they were given an invaluable insider’s tip from Dr. Graham. When the Master Wizard of drug safety says, “Stop,” it’s pure folly to say, “Go.”

Remember the Vioxx scandal? Long before Merck pulled Vioxx from the market, Dr. Graham warned that the drug increased heart attack risk. For his diligence, Dr. Graham was publicly criticized by FDA officials, most notably by Dr. Robert J. Meyer of the FDA’s Center for Drug Evaluation and Research, who seems to constantly play the role of Draco Malfoy to Dr. Graham’s Harry Potter. Dr. Meyer’s department approves drugs and Dr. Graham often shoots them down.

As I’ve noted in previous e-Alerts, Dr. Graham has frequently been the loudest voice warning the FDA and Congress about unsafe drugs – such as the antibiotic Omniflox (pulled from the market in 1992), Rezulin (a diabetes drug pulled in 2000), and others.

Time and again Dr. Graham has been vindicated, as he was so dramatically with Vioxx. Will this new FDA panel decision on Avandia eventually be vindicated, or will it soon become another FDA embarrassment, courtesy of Dr. Graham’s research?

I know who I’m betting on.