ARON BROWN, CNN ANCHOR: Good evening again everyone. Drugs, the legal ones, are a huge business in the country and a huge part of our lives. The question on the table tonight is simple, though the answer is not. Is the government doing its job keeping the pipeline of good drugs open and keeping the dangerous ones off the market?
Vioxx, the pain medication pulled by Merck because of increased risk of heart attack, is the best current example. To critics of the FDA it is the tip of the iceberg.
A survey of FDA scientists found that two-thirds are less than fully confident in the safety of drugs on the market. Nearly 20 percent said they felt pressure to approve drugs they thought might be unsafe.
In a moment, the FDA’s leading critic, a 20-year employee, Dr. David Graham, first some background from CNN’s Elizabeth Cohen.
ELIZABETH COHEN, CNN MEDICAL CORRESPONDENT: Tillman and Mary Harris were married for 47 years, raised a daughter, had grandchildren.
UNIDENTIFIED FEMALE: I miss him terribly, wish he were here.
COHEN: Tillman Harris isn’t here because after taking a cholesterol-lowering drug called Baycol, he developed an unusual muscle wasting condition called rabdomyolysis. He became so weak his wife and daughter rushed him to the hospital where he died ten days later.
Six months after his death, Bayer pulled Baycol off the market. At that point, 31 people taking the drug had died of rabdomyolysis. And now the question is could Bayer have prevented those deaths?
Tillman Harris died in February, 2001. In March, 2000, nearly a year earlier, an internal Bayer memo that was quoted in the journal of the American Medical Association this month stated: “Baycol substantially elevates the risk for rabdomyolysis compared with other cholesterol-lowering drugs.”
Dr. Jerry Avorn is a professor at Harvard Medical School and author of the book “Powerful Medicines.”
DR. JERRY AVORN, AUTHOR, “POWERFUL MEDICINES”: Baycol is one of several drugs that we are asking ourselves how in the world did this drug stay on the market as long as it did?
COHEN: The answer, he and others say, is complicated. When drug companies hear of serious side effects they have to by law report them to the Food and Drug Administration but connecting the dots and analyzing the data is time consuming.
AVORN: They haven’t had the person power to receive and deal with all of these thousands and thousands of spontaneous reports that the companies send in.
COHEN: If a drug company finds a side effect before a drug goes on the market
COHEN: If a drug company finds a side effect before a drug goes on the market, it legally has to show that study to the FDA but the law prevents the FDA from making those studies public. Drugs companies say the studies contain trade secrets. Pharmaceutical companies say they reliably report side effects both before and after a drug is put on the market.
ALAN GOLDHAMMER, PH.D., ASSOC. V.P. FOR REGULATORY AFFAIRS: These are significant reporting requirements that companies engage on, on an ongoing basis.
COHEN: Concerning Baycol, Bayer says they kept the FDA fully informed about all pertinent safety information, including adverse event reports. When Bayer became aware of an increased rate of reports of rabdomyolysis it took appropriate action. But the Harris family is left wondering what if Bayer, what if the FDA had taken quicker action before there were 31 deaths.
ROSE HARRIS, DAUGHTER: Somewhere between the one and the 31 there were probably people who wouldn’t have passed away.
BROWN: It’s a reality, if not always a welcome reality that stories like this one rarely take off until there’s a media moment, if you will, even if a lot of people are hurt, some die, moments like the Army reservist in Kuwait or, in this case, an FDA whistleblower testifying before the Congress.
DR. DAVID GRAHAM, FDA SCIENTIST: I was pressured to change my conclusions and recommendations. One drug safety manager recommended that I should be barred from presenting the poster at the meeting and also noted that Merck needed to know our study results.
BROWN: That was Dr. David Graham and Dr. Graham joins us from Washington tonight. Sir, it’s nice to see you. GRAHAM: Thank you.
BROWN: I suppose to one degree or another all drugs on the market have some risk associated with them and presumably if they got to market they have some reward. Is the basic allegation that you make that this risk/reward balance is out of balance at the FDA? They’re more concerned about reward than the risk.
GRAHAM: That’s partially correct. What I maintain is, is that the FDA places almost complete attention and focus and value on what they perceive to be the benefit of a product and discount almost completely the risk side, the safety side, a consequence of a drug.
But, in addition to that, they don’t adequately measure what the actual benefit of a drug
But, in addition to that, they don’t adequately measure what the actual benefit of a drug is. When a clinical trial is done they’re measuring what is called the effect of the drug.
The effect of a drug is sort of does it lower your blood cholesterol? Does it lower your blood pressure? Does it lower your blood sugar? That would be the effect of a drug. The benefit of the drug is would it help you to live longer, to live healthier?
And, FDA only measures efficacy. It doesn’t measure benefit and yet when a safety problem emerges there we’re talking about real lives lost, real lives ruined. FDA typically places a very high value on the efficacy and translates that into saying there’s a benefit when they have no established evidence of a benefit and this was the case with Vioxx (UNINTELLIGIBLE) Vioxx.
BROWN: I want to talk about Vioxx a little bit here and perhaps drugs generally as well. In the case of Vioxx, first of all, the number 100,000 heart attacks and the like has been thrown out. Are those actual people or is this a statistical model? Is it a best guess? Do we actually know the names of 100,000 people?
GRAHAM: Well, no. We don’t know the names of 100,000 people. The government does this all the time in epidemiology, which is you can’t be out there with people counting every person who has a heart attack from Vioxx.
So you take the data that you have at hand, such as the clinical trials that Merck did that showed that Vioxx increased the risk of heart attack for high dose Vioxx 500 percent or the lower dose Vioxx by 200 percent.
And then you determine how many people were treated with the high and the low dose and it’s a very simple matter then to calculate out the number of heart attacks that would have resulted.
BROWN: Is it a larger we seem to take drugs longer. We’re on anti-cholesterol drugs the rest of our lives that sort of thing. Is the problem greater in drugs that are on the market or drugs coming to the market?
GRAHAM: Well, there are several aspects to that question. FDA when it’s looking at a drug for the pre-approval side before it comes to the market says that a drug is both safe and effective before they put it on the marketplace.
Well, they’ve got the efficacy part right. There they’re 90 percent sure or better that the drug works. But when it comes to safety, they’re not 95 percent sure that the drug is safe. Instead, what FDA is really saying is, is we don’t have 95 percent confidence that the drug will kill you and that’s a very different standard.
Now, on the post approval side, once a drug gets to the market drugs that are widely marketed, your blockbuster drugs have the potential theoretically at least to effect a much wider number of patients and with Vioxx that was precisely the reason why so many people were hurt by the drug.
It was a blockbuster drug
It was a blockbuster drug. It increased the risk of heart attack by a very large amount and heart attack itself is a fairly common event in the general population. You put those things together and you have the formula for a national disaster.
BROWN: Is this about money in the end that the drug industry is powerful, that the agency in your view, people disagree with this I assume, is just simply too close to the industry it’s supposed to regulate?
GRAHAM: My own view, and I’m not speaking for the agency of course, is that FDA views industry as its client and this is official FDA, not the FDA scientists. You mentioned the survey in your lead-in to our interview and there we see that many FDA scientists have experienced what I’ve experienced and that they realize and recognize that FDA is not doing what it needs to do to protect Americans from unsafe drugs.
In fact, I think what that survey demonstrates is, is that FDA is more interested in serving its business clients than it is from protecting the American public from unsafe drugs.
BROWN: There’s another way to look at that. I mean in the I think it was 18 percent of scientists said they felt some pressure to approve a drug they felt was unsafe. That means there is 80 percent who did not feel that pressure and how ought we look at that number?
GRAHAM: I think the American people should be appalled by the thought that only 82 percent felt no pressure to change their opinion. Think about this. FDA is a scientific organization. In a scientific organization, the science should speak for itself. No one should feel pressured to change their opinion.
The fact that you’ve got 18 percent of FDA scientists saying that they felt this pressure is an appalling statistic but consider this also. Most drugs that FDA reviews don’t have safety problems to begin with. They’re me-too drugs, so they’re very similar to other drugs that are already on the market where the problems have already been worked out.
So, the majority of drugs that FDA reviews nobody has a question about them, so we’re talking about a subset and in that subset, that subset might just be 18 percent of the drugs that FDA sees and then what you can see is that virtually all the drugs where there is a question about safety, if the scientist raises that question, that scientist will experience pressure to change their opinion.
GRAHAM: So, it’s a misleading statistic.
BROWN: I’m sorry. Dr. Graham, just as a final question, let’s talk about the pressure a little bit. Since you testified before Congress or since it was clear you were going to testify before Congress, have they pretty much put you in a closet?
GRAHAM: Well, my supervisors have canceled all their meetings with me. Yesterday I was at a research seminar that we hold in our department and one of our senior managers came into the meeting and there was one empty seat, which was next to me. I greeted this manager with a hello and the manager just basically looked the other way, sat in the seat and didn’t say a word to me the entire meeting.
So, it’s basically being put into the gulag out in Siberia. I have plenty of work to do and I’m happy to do it and I do it well and my colleagues are very pleased to have me there to help them do the important business of monitoring drug safety in the United States.
BROWN: And we’re happy you were with us tonight. We appreciate your time. Thank you, sir, very much.
GRAHAM: Thank you very much.
BROWN: Dr. David Graham, who has been at the FDA for 20 years, his view of the agency.
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