Life Extension Magazine October 2012
As We See It
The FDA Exposed: An Interview With Dr. David Graham, the Vioxx® Whistleblower
The following interview with Dr. David Graham (senior drug safety researcher at the FDA) was conducted by Manette Loudon, the lead investigator for Dr. Gary Null. This interview contains jaw-dropping insights about the corruption and crimes that take place every day inside the Food and Drug Administration. This is no outside critic, either: these are the words from a top FDA employee who has worked at the agency for two decades. If you've ever wondered how the drug industry could pull off the greatest con of our time—and turn the human body into a profit-generating machine—you're about to learn the shocking answers in this interview.
This interview is reprinted here with permission from Dr. Gary Null. What you may find particularly troubling is that this interview was conducted in 2005, yet little has changed within the FDA to correct these atrocities.
MANETTE: Dr. Graham, it's truly a pleasure to have the opportunity to interview you. Let me begin by asking you how long you've been with the FDA and what your current position is?
DR. GRAHAM: I've been with the FDA for 20 years. I'm currently the Associate Director for Science and Medicine in the Office of Drug Safety. That's my official job. But when I'm here today I'm speaking in my private capacity on my own time, and I do not represent the FDA. We can be pretty certain that the FDA would not agree with most of what I have to say. So with those disclaimers you know everything is okay.
MANETTE: On November 23, 2004 PBS Online News Hour Program you were quoted as making the following statement. "I would argue that the FDA, as currently configured, is incapable of protecting America against another Vioxx®. Simply put, FDA and the Center for Drug Evaluation Research (CDER) are broken." Since you've made that statement, has anything changed within the FDA to fix what's broken and, if not, how serious is the problem that we're dealing with here?
DR. GRAHAM: Since November, when I appeared before the Senate Finance Committee and announced to the world that the FDA was incapable of protecting America from unsafe drugs or from another Vioxx®, very little has changed on the surface and substantively nothing has changed. The structural problems that exist within the FDA, where the people who approve the drugs are also the ones who oversee the post marketing regulation of the drug, remain unchanged. The people who approve a drug when they see that there is a safety problem with it are very reluctant to do anything about it because it will reflect badly on them. They continue to let the damage occur. America is just as at risk now, as it was in November, as it was two years ago, and as it was five years ago.
MANETTE: In that same PBS program, you were also quoted saying, "The organizational structure within the CDER is currently geared towards the review and approval of new drugs. When a serious safety issue arises at post marketing, the immediate reaction is almost always one of denial, rejection and heat. They approved the drugs, so there can't possibly be anything wrong with it. This is an inherent conflict of interest." Based on what you're saying it appears that the FDA is responsible for protecting the interests of pharmaceutical companies and not the American people. Do you believe the FDA can protect the public from dangerous drugs?
DR. GRAHAM: As currently configured, the FDA is not able to adequately protect the American public. It's more interested in protecting the interests of industry. It views industry as its client, and the client is someone whose interest you represent. Unfortunately, that is the way the FDA is currently structured. Within the Center for Drug Evaluation and Research about 80 percent of the resources are geared towards the approval of new drugs and 20 percent is for everything else. Drug safety is about five percent. The "gorilla in the living room" is new drugs and approval. Congress has not only created that structure, they have also worsened that structure through the PDUFA, the Prescription Drug User Fee Act, by which drug companies pay money to the FDA so they will review and approve its drug. So you have that conflict as well.
MANETTE: When did that go into effect?
DR. GRAHAM: The Prescription Drug User Fee Act came into play in 1992. It was passed by Congress as a way of providing the FDA with more funds so that it could hire more physicians and other scientists to review drug applications so that drugs would be approved more quickly. For industry, every day a drug is held up from being marketed, represents a loss of one to two million dollars of profit. The incentive is to review and approve the drugs as quickly as possible, and not stand in the way of profit-making. The FDA cooperates with that mandate.
MANETTE: And what about those new drugs? Are they any better than what already exists on the market?
DR. GRAHAM: It's a myth that is promulgated not only by industry but also by the FDA itself. It's a misperception that our lawmakers in Congress have as well and they've been fed this line by industry. Industry is saying there are all these lifesaving drugs that the FDA is slow to approve and people are dying in the streets because of it. The fact is that probably about two-thirds to three-quarters of the drugs that the FDA reviews are already on the market and are being reviewed for another indication. So, for example, if I've got a drug that can treat bronchitis and now it's going to be used to treat a urinary tract infection well, that's a new indication. But it's the same drug and we already know about the safety of the drug. There is nothing lifesaving there. There is nothing new. There is nothing innovative. A very small proportion of drugs represent a new drug that hasn't been marketed before. Most of those drugs are no better than the ones that exist. If you want to talk about breakthrough drugs - the ones that really make a difference in patients' lives and represent a revolution in pharmacology - we're talking about maybe one or two drugs a year. Most of them aren't breakthroughs and most of them aren't lifesaving, but they get treated as if they were.
MANETTE: Are you at liberty to discuss some of the problems your colleagues are finding with other drugs and if so, how widespread is the problem?
DR. GRAHAM: I'm really not at liberty to talk about things that pertain to my official duties at the FDA. I can talk in my private capacity, but I can't talk about material that would be confidential. What I can say is that there are a number of other scientists within the FDA who have also worked with drugs that they know are not safe, even though the FDA has approved or allowed them to remain on the market. They face some of the same difficulties that I do. The difference is that either the problem isn't as serious in terms of the numbers of people that were injured or that it's a fatal reaction - they're not willing to expose themselves to retaliation by the FDA - and retaliation would surely follow.
MANETTE: Do you think we should have any confidence in the FDA and if so, can you elaborate on what they do that you feel benefits the American people?
DR. GRAHAM: In terms of confidence in what the FDA does, there are two things that the FDA determines when it looks at a drug: it determines whether or not a drug is safe and it determines whether or not it's effective. Regarding the determination of drug effectiveness, I think the FDA does a pretty good job. If the FDA says that the drug will have a particular effect, probably for many of the patients who take the drug it will actually have that effect. If the FDA says a given drug will lower blood pressure and you're somebody who has high blood pressure, there's a good chance that the drug will have an effect that lowers your blood pressure. That has to do with the rigor with which they force the drug companies to establish that the drug actually has an effect.
On the safety side, I think that the American public can't be very confident. They can have some confidence because it turns out that most drugs are remarkably safe. But, when there are unsafe drugs, the FDA is very likely to err on the side of industry. Rarely will they keep a drug from being marketed or pull a drug off the market. A lot of this has to do with the standards that the FDA uses for safety. When they look at efficacy, they assume that the drug doesn't work and the company has to prove that the drug does work. When they look at safety it's entirely the opposite. The FDA assumes the drug is safe and now it's up to the company to prove that the drug isn't safe. Well, that's a no-brainer. What company on earth is going to try to prove that the drug isn't safe? There's no incentive for the companies to do things right. The clinical trials that are done are too small, and as a result it's very unusual to find a serious safety problem in these clinical trials. Safety flaws are discovered after the drug gets on the market.
MANETTE: I read somewhere that a drug only has to be better than a sugar pill
DR. GRAHAM: Right. The standard that the FDA uses to approve a drug is primarily "does the drug work?" That's what they call efficacy. Most often, they'll compare the drug against something called a placebo or a sugar pill. It's basically something that doesn't have a medical effect. The assumption is that the drug will be no different than the sugar pill. The FDA puts the onus on the drug company to conduct a clinical trial to show that the drug is different from a sugar pill. The way the FDA's approval standards are, the drug does not necessarily have to have a very great effect in order to be approved. The drug might lower your blood pressure by just a few millimeters of mercury, but the FDA will say we can approve it because it does lower your blood pressure.
Now, would that be a benefit or are there other drugs out there - many other drugs - that patients could take instead that would lower their blood pressure by 10 or 15 or 20 millimeters? The FDA doesn't really care about that. What happens is the drug gets marketed. You've got two drugs that are out there - one drug that effectively lowers your blood pressure a substantial degree and another drug that barely lowers your blood pressure at all. The company that has that second drug markets it like it's this breakthrough medicine. It lowers your blood pressure and they have all these glitzy ads, direct-to-consumer advertising. Lots of patients and lots of doctors will use that medication. What happens in the process is these patients are actually in a sense being denied a more effective treatment because the FDA doesn't require that drugs that come on to market be at least equivalent to, or better than, the drugs that are already there. All they have to do is be better than a sugar pill.
MANETTE: When you consider the financial impact your whistle blowing has had on the pharmaceutical industry do you have any fears that your life may be in jeopardy?
DR. GRAHAM: I have tried not to think about that. In the work that I've done I've never really thought about what the financial impact would be on any particular company. I put that out of my mind because my primary concern is whether or not the drug is safe. If it's not safe, how unsafe is it and how many people are being hurt by it? In terms of when I identify an unsafe drug, to me it doesn't really matter what drug company it is. I've helped to get ten different drugs off the market, and they're from ten different drug companies. It's not a vendetta against any particular drug company. I have to hope that the drug companies don't take it personally. I'm just a scientist doing my job and I have to leave the rest to God to protect me.
MANETTE: Has anyone tried to silence you and stop you from becoming a whistleblower?
DR. GRAHAM: Prior to my Senate testimony in mid-November of 2004, there was an orchestrated campaign by senior level FDA managers to intimidate me so that I would not testify before Congress. This intimidation took several forms. One attack came from our acting Center Director who contacted the editor of the Lancet, the prestigious medical journal in the United Kingdom, and intimated to the editor that I had committed scientific misconduct and that they shouldn't publish a paper that I had written showing that Vioxx® increases the risks of heart attack. This high-level FDA official never talked to me about this allegation. He just went directly to the Lancet.
The second attack was from other high level FDA officials who contacted Senator Grassley's office and attempted to prevent Senator Grassley and his staff from supporting me and calling me as a witness. They knew that if they could disarm Senator Grassley that would neutralize me.
The third attack came from senior FDA officials who contacted Tom Devine, my attorney at the Government Accountability Project, and attempted to convince him that he should not represent me because I was guilty of scientific misconduct; I was a bully; a demigod; and a terrible person that couldn't be trusted. These people were posing as whistleblowers themselves ratting on another whistleblower. Some of these senior level FDA officials were in my supervisory chain and are people I work for. They were involved in a coordinated attempt to discredit me and to smear my name and to prevent me from giving testimony.
There's one other thing that happened the week before I testified. The Acting Commissioner of the FDA invited me to his office and offered me a job in the Commissioner's Office to oversee the revitalization of drug safety for the FDA if I would just leave the Office of Drug Safety and come to the Commissioner's Office. Obviously he had been tipped off by people in the Senate Finance Committee who are sympathetic to the FDA's status quo that I was going to be called as a witness. To preempt that, he offers me this job, which basically would have been exile to a fancy title with no real ability to have an impact. This was a conspiracy and it was coordinated and there was collaboration among senior level FDA officials. What a mess!
MANETTE: All of these attacks backfired on them. Tell us a little bit about that.
DR. GRAHAM: Well, Senator Grassley and his staff quickly realized that what they were saying about me was fabricated. The editor of The Lancet also realized that what the high level FDA officials were saying to him was a pack of lies. He sent emails to them saying it looked to him as if they were trying to interfere with his editorial process. He was very savvy to what these people were doing. Tom Devine, as he said publicly, was very interested in doing the right thing. He said, "We don't want to protect somebody who's a lawbreaker and who really isn't representing the truth so produce your evidence." They had no evidence because there is no evidence. But I produced my evidence. I showed him all the documentation, all the emails, and the reports that I've written. They flunked every test and I passed every test.
In all of the criticism I have received relating to Vioxx® and drug safety, they've never attacked the work or the science that I've done or the results that I've come to. What they've done is call me names. The ad hominem attack is the last refuge of the indefensible. They don't have an argument that's substantial. They know that they're vulnerable. They know that they've disserved the American people. The FDA is responsible for 140,000 heart attacks and 60,000 dead Americans. That's as many people as were killed in the Vietnam War. Yet the FDA points the finger at me and says, "Well, this guy's a rat, you can't trust him," but nobody is calling them to account. Congress isn't calling them to account. For the American people, it's dropped off the radar screen. They should be screaming because this can happen again.
MANETTE: On CNN with Lou Dobbs you said that there was a certain "culture" that exists at the FDA. Can you explain what you meant by that?
DR. GRAHAM: The FDA has a very peculiar culture. It runs like the army so it's very hierarchal. You have to go through the chain of command and if somebody up above you says that they want things done in a particular way well, they want it done in a particular way. The culture also views industry as the client.
They're serving industry rather than the public. In fact, when a former office director for the Office of Drug Safety criticized me and tried to get me to change a report I'd written on another drug - Arava - he said to me and to a colleague who was a coauthor on this report that "industry is our client." I begged to differ with him. I said, "No, industry is not the client, it's the American people, the people who pay our taxes. That's who we're here to serve." He said, "No! Industry is our client." I ended the conversation by saying, "Well, industry may be your client, but it will never be my client."
Another aspect to the culture at the FDA is that it overvalues the benefits of drugs and undervalues the risks of drugs. And so the FDA will always say to you, "Well, we're leaving this drug on the market because the benefits exceed the risks." Well, the FDA has never assessed the benefit of any drug that it's ever approved. It works on what's called efficacy. Does the drug work or not? Does it lower your blood pressure or does it lower your blood sugar? Not: Does it prolong your life? Does it prevent you from having a heart attack? Those are benefits. All they focus on is efficacy.
For example, ask the FDA why on earth they didn't ban high dose Vioxx® after the VIGOR Study showed in early 2000 that it increased the risk of heart attack by 500 percent? High dose Vioxx® was approved for the short-term treatment of acute pain. What earthly benefit was there that exceeds a 500 percent increase in heart attack risk? Ask the FDA to produce its benefit analysis that shows that the benefits exceed the risks. It doesn't exist. The FDA has never looked at benefit. The FDA just says to the American people, "The benefits exceed the risks. Trust me. Believe me." If you held the FDA to its proof the American people would see how badly served they've been by the FDA and its culture that belittles safety in the drug companies' interest.
If the FDA were to pull a drug due to safety issues, it would hurt the marketing of the drug. It might also call into question why they approved the drug in the first place. Therefore, you get this culture of cover-up, this culture of suppression, this culture of denial, and this culture that demonstrates above all else that industry is the client and not the American people.
MANETTE: Have your peers turned against you?
DR. GRAHAM: No. I've been very fortunate. Tom Devine at GAP has told me that the experience of a typical whistleblower is that they'll have the support of their peers but the peers will be so afraid of retaliation that they won't express that support in public. I've had a very different experience. I've been basically embraced by my peers as someone who has said what they want to say and what they wished they had been able to say and that they recognize as the truth. They're really proud of the fact that I've said it and they're not afraid to be seen with me. They're not afraid to work with me. I've been pretty fortunate in that way.
Now with management it's been another story. Upper management avoids me and doesn't talk to me. I could be walking down the hall and I'll say hello, and they'll act like I'm not there. They don't give me interesting work assignments. They don't call me in to consult on things that I should be consulted on even though I am the senior epidemiologist in the Office of Drug Safety with more experience than any of the other people there. I'm looked up to by the scientific staff because of that expertise. Basically, I feel like I'm in the Gulag.
MANETTE: How do you cope with that going to work each day?
DR. GRAHAM: It's difficult. It's a mind game. They're hoping that I'll just become very frustrated and disillusioned and leave or that I'll slip up in some way so that they can take some sort of action against me. As Tom Devine at GAP has said, I have to be Saint David. I can't afford to make any mistakes. That's very difficult and it is a little bit discouraging. But I've been a target of retaliation in the past. You take ten drugs off the market well, no good deed goes unpunished at the FDA. I've experienced retaliation with many of those other episodes but not as severe as what I've experienced with Vioxx®. This is the first time that my job was actually in jeopardy and where the FDA actually intended to fire me. That was stopped only because Senator Grassley intervened. He put the heat on the FDA and told them, "Lay off. This guy has told the truth. He's helped America. Whose side are you on?"
MANETTE: Were there any warnings that Vioxx® was a problem? Did you see the disaster coming?
DR. GRAHAM: I think that I was afraid that there would be a disaster, but I only became aware of this with the publication of the VIGOR Study, which was this large clinical trial that was done that showed that Vioxx® increased the risk of heart attack five-fold. That study was published in November of 2000. It was written, performed, and paid for by industry. What industry concluded was not that Vioxx® increases the risks of heart attack, but that the drug they were comparing it against—Naproxen®—decreased the risk of heart attack. I knew that was not a sustainable argument. There was no way that Naproxen® was that protective against heart attacks. Clearly Vioxx® was the problem. I knew that Vioxx® was on the road to becoming a blockbuster drug (20 million users). All the ingredients were there for a disaster.
The FDA is responsible in so far as it could have prevented much of the damage, heart attacks, and deaths simply by banning the high dose Vioxx® back in mid 2000 when they knew the results of the VIGOR Study. But the FDA did nothing for almost two years. They were "negotiating" with the company over a label. What did the label accomplish? Nothing! Before the label 17 or 18 percent of people who took Vioxx® took the high dose. After the label change 17 or 18 percent were still taking the high dose. High dose use didn't change at all. People didn't read the label, and if they read the label they wouldn't know what to do anyway because it was very confusing. The right thing to do would have been to pull the high dose off the market because there is no benefit for short-term relief of acute pain that exceeds this risk. The FDA made bad decisions based on its culture and its institutionalized biases that favor industry, and as a result thousands of Americans died. Americans and Congress should be screaming bloody murder. They should be beating on the doors of the FDA demanding change.