Truth or Consequences at the FDA

Sometimes, as bad as you think things are, it turns out they’re actually worse.

Welcome to Bushworld Part Deux, where government agencies that are supposed to protect the public provide nothing more than a weak façade while thousands pay the price in illness and death. Think I’m exaggerating? You may have been hearing about the Vioxx scandal. Vioxx is the best-selling pain reliever that was recently withdrawn by Merck, its producer, but only after it has caused heart attacks in an estimated 88,000 to 139,000 Americans, 30-40% of whom probably died.

According to the fascinating, but disturbing testimony last week of FDA’s David Graham, Associate Director for Science and Medicine in FDA’s Office of Drug Safety,

Today, in 2004, you, we, are faced with what may be the single greatest drug safety catastrophe in the history of this country or the history of the world. We are talking about a catastrophe that I strongly believe could have, should have been largely or completely avoided. But it wasn’t, and over 100,000 Americans have paid dearly for this failure. In my opinion, the FDA has let the American people down, and sadly, betrayed a public trust.

***

The problem you are confronting today is immense in scope. Vioxx is a terrible tragedy and a profound regulatory failure. I would argue that the FDA, as currently configured, is incapable of protecting America against another Vioxx. We are virtually defenseless.

That’s reassuring. And what was the response of the Bush administration’s man at the FDA?

Dr. Steven Galson, director of the agency's Center for Drug Evaluation and Research, charged that some of Dr. Graham's conclusions "constitute junk science" and were "irresponsible."

Yeah, telling the truth is irresponsible, but killing up to 55,000 Americans is, what? Freedom of the marketplace?

Oh, but how was Merck and the FDA to have known? Turns out in 2000, Merck did a study showing that when compared with the pain reliever naproxin, Vioxx caused 5 times as many heart attacks as those who took naproxin. Alarm bells? Hardly. Merck just concluded that naproxin must be highly protective.

According to GWU Professor David Michaels, speaking at a recent American Public Health Association forum, if Naproxin were that good at preventing heart attacks, we’d be putting it in the water.

And where was FDA while this and other studies showing similar results were going on? Turns out that FDA, once it approves a drug is highly reluctant to withdraw it. According to Graham,

When it comes to safety, the OND (Office of New Drugs) paradigm of 95% certainty prevails. Under this paradigm, a drug is safe until you can show with 95% or greater certainty that it is not safe. This is an incredibly high, almost insurmountable barrier to overcome. It’s the equivalent of “beyond a shadow of a doubt.” And here’s an added kicker. In order to demonstrate a safety problem with 95% certainty, extremely large studies are often needed. And guess what. Those large studies can’t be done.

There are 2 analogies I want to leave you with to illustrate the unreasonableness of CDER’s (Center for Drug Evaluation and Research) standard of evidence as applied to safety, both pre- and post-approval. If the weather-man says there is an 80% chance of rain, most people would bring an umbrella. Using CDER’s standard, you wouldn’t bring an umbrella until there was a 95% or greater chance of rain.

The second analogy is more graphic, but I think it brings home the point more clearly. Imagine for a moment that you have a pistol with a barrel having 100 chambers. Now, randomly place 95 bullets into those chambers. The gun represents a drug and the bullets represent a serious safety problem. Using CDER’s standard, only when you have 95 bullets or more in the gun will you agree that the gun is loaded and a safety problem exists. Let’s remove 5 bullets at random. We now have 90 bullets distributed across 100 chambers. Because there is only a 90% chance that a bullet will fire when I pull the trigger, CDER would conclude that the gun is not loaded and that the drug is safe.

That’s reassuring.

Now let me say something about Graham. He’s a “government bureaucrat” not a wild-eyed public interest bomb thrower. Just doing the job like it’s supposed to be done. And he’s been doing it for twenty years:

To those who have closely followed the agency, his comments could not have come as much of a surprise. Dr. Graham has been making similar warnings for most of his 20-year career there.”

A physician trained at Johns Hopkins and Yale, Dr. Graham, 50, has spent his entire professional life in the agency's Office of Drug Safety, which monitors reports of adverse events for approved medicines and tries to determine whether drugs now on the market are as safe as initially thought.

Widely acknowledged as whip-smart and well prepared, he is a Roman Catholic and a strong opponent of abortion. On his wall is a picture of Jesus calling Peter and Andrew to be his disciples. When he works, he often glances at it, "and it reminds me why I'm here," he said in an interview on Friday.

Dr. Graham has six children and is an assistant scoutmaster for a Boy Scout troop. He said his faith had served as the spur and guide for much of his work. He has often been told to tone down his conclusions, to get on the team, he said. He has refused. "We all have a responsibility to honor the truth," he said.

There are still a log more government employees like Dr. Graham in the federal government. But more and more are leaving or being forced out, frustrated by the political domination of the agencies that are supposed to protect public health by the industries they are supposed to be regulating.

This is the so-called evil "big government" that the Republican spinmeisters use to scare the unknowledgeable American public. But their concern isn't really about about "big government" intruding on the lives of private citizens; what they're upset about is government agencies that enforce the laws as they were intended to be used; to put effective obstacles in the way of profits over public health. And after eight years of ignoring and harassing those who take their public responsibility seriously, what will be left?

These are the stories that the American people need to hear. Not just about the "evil" drug companies, but about a federal government controlled by those who are giving the green light to the the irresponsible.