The Side Effects of Truth
In exposing the deadly threat posed by Vioxx, FDA researcher David Graham was serving the public interest. His bosses had other interests in mind.
DR. DAVID GRAHAM IS LOSING WEIGHT AGAIN. His wife noticed first, then his colleagues at the Food and Drug Administration. Graham is a skinny man, and when he drops weight, his cheekbones seem to sit higher on his face. His striped cotton shirts, the frumpy uniform of a government scientist, hang more loosely on his narrow frame. But he isn't eating, and no wonder: Graham, the scientist who brought the Vioxx scandal to the nation's attention, feels like a marked man.
"I'm no longer welcome," he says, sitting in a Rockville, Maryland, coffee shop in early February. He has just left another frustrating day at work, where his boss warned him not to disclose new safety findings about a popular class of painkillers called Cox-2 inhibitors. In a few minutes, he is due at his son's Boy Scout meeting, but all he can talk about now is the exhaustion of working in a drug-safety system in turmoil. "I'm hoping things will calm down, but I don't think the FDA will let that happen," he says. "How do you get off the merry-go-round?"
In August 2004, Graham told his supervisors that, in light of his research, high-dose prescriptions of the painkiller Vioxx, which appeared to triple heart attack rates, should be banned. They told him to be quiet. Their reasoning was circular: That's not the FDA's position; you work here; it can't be yours. Dr. John Jenkins, the FDA director of new drugs, argued that because Graham's findings didn't replicate the drug's warning label, Graham shouldn't be raising the warning. Another supervisor, Anne Trontrell, called Graham's position "particularly problematic since FDA funded this study." Days after Graham's pronouncement, the agency approved Vioxx for use in children.
But Graham was right. The following month, Merck pulled Vioxx from the market after its own research found that the drug, even when taken at low dosages, doubled the risk of heart attack. The announcement provided Graham no vindication. With a scandal on the horizon, the FDA brass now saw him as a danger. They couldn't silence the message, so they tried to take out the messenger.
Dr. Steven K. Galson, the acting director of the drug-evaluation division at the FDA, told reporters that Graham's work "constitutes junk science." Then he sent an email to an editor at the prestigious British medical journal The Lancet, questioning the "integrity" of Graham's data—a suspicion that proved baseless. The FDA's acting commissioner, Dr. Lester Crawford, criticized Graham for evading the agency's "long-established peer review and clearance process." Another official made calls to at least one Senate staffer, disparaging Graham personally and professionally.
Eventually, he was heard. In November he went before the Senate Finance Committee hearing on Vioxx. Gaunt (he'd lost 12 pounds over three months) but very lucid, Graham took his place before a bank of cameras, wearing his only sport coat, a 20-year-old blue blazer with brass buttons. He explained his conclusion that patients taking high doses of Vioxx were suffering heart attacks. "The estimates range from 88,000 to 139,000 Americans," he said. "Of these, 30 to 40 percent probably died. For the survivors, their lives were changed forever." According to the top end of those projections, the toll Vioxx had already taken was comparable to the number of Americans killed in Vietnam. "The FDA, as currently configured," Graham told the committee, "is incapable of protecting America against another Vioxx. We are virtually defenseless."
But three months later, as Graham sips iced tea in a Rockville cafe, the FDA is again trying to suppress his research, this time on the effects of pain medications similar to Vioxx. "I think we've already articulated our preference," his supervisor, Dr. Paul Seligman, wrote him in a terse email. The agency doesn't want Graham presenting his latest research to scientists who will be meeting in a few days to discuss the drugs.
David Graham is headstrong, but not insubordinate. He cannot afford to lose his job. His family has just moved to a new house. His wife, Nancy, stopped working as a lawyer so she could homeschool their six children. Really, though, he has no more time to sit here worrying. The Boy Scouts are competing for their merit badges this evening. He finishes his iced tea.
"I've made a commitment," he says, before walking out the door. "I'll weigh myself this evening."
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Disclaimer: I do not work for Big Pharma.
Problem with scientists like Graham is that they work from mortality data.
Yes, Vioxx had a significant impact in increasing heart attack risk, but for a very small minority of patients using it.
Had he used a bit of molecular smarts, he would have looked deeper into the mechanism behind this risk.
Its related to the risk for Avandia, and nother hoopla that has relatively easy fixes - IF you know the nuclear receptor causes, and the identifier symptoms that predispose a subset of patients to much higher risk than is acceptable.
Rather than remove these drugs from open market use, futher work should be done to demarcate the vulnerable patient subset and then appropriate precautions can be used to reduce their risk (or find other medications OR heaven forbid, correct their conditions by alternative medicine practices.
What we have is a well intentioned induhvidual who simply doesn't know his molecular biology very well. Too bad, because he is good at finding patterns in test cohort data that points to dangerous side effects.
Time to start connecting the dots. I'm telling you outright - you CAN identify the molecular mechanisms behind side effects and use additional steps to further reduce that risk to patients by direct or indirect intervention.
And, its high time we found diagnostics that identify patients susceptible to side effects from medications that otherwise are critical for patient treatment for a variety of chronic conditions.
For this reason, I can't condone the approach Graham uses to voice his disapproval of the drug testing and approval system here in the US. He still has his job - only the most lenient of managers would have kept him on, rather than firing him for insubordination.
Just as an aside, what the hell is this man doing with 6 kids?? Ever hear of overpopulation, Dr Graham?
You probably do work for Big Pharma. You must be one of those "Internet Watchdogs" I have been hearing so much about, or one of the 600 lobbyists that they employ. I am grateful that somebody is out there looking out for the consumer.
Mr. Smith, I do not personally know you, nor do I know what scientific background you may have, nor do I know for whom you work, however I do know Dr. Graham, as he is my father. I can understand that you may view any complications of taking medications to be very easily curtailed before they become serious enough to bring death into consideration. However, while you may be aware of the symptoms that would denote a dangerous reaction to medication, most people do not, and many of the symptoms can be explained by other causes. And until every person on any given medication is required to gain some sense of medical diagnostics, I think it is vital that someone else act on their behalf. As to the question of overpopulation, that comment has no bearing on the issue and is personally offensive to me. I accept that having six children, or any children for that matter, may not be an acceptable choice in your life, but do not presume to know the ins and outs of my father's life.
Mr. Smith, I suspect you are a wack job no doubt paid to submit an article written by someone else. I wonder why you felt it necessary to add your completely irrelevant, ignorant and rather vicious opinion on Dr. Graham's six children. You'd already lost any credibility you may have had with your use of the word "induhvidual."
Dr. Graham is a very brave and ethical man and I am grateful to him and thankful there are still some Americans who will take a stand and risk all to right a wrong.
It is of great benefit to patients that there is someone who is prepared to question safety issues concerning new drugs. When Vioxx was developed, its manufacturer was anxious to gain a share of the expanding osteoarthritic pain relief market. Developing a product that will service a chronic condition is the pot of gold at the end of the pharmaceutical rainbow. Increasing sales is, of course, not a problem in itself. However, when those sales are achieved at the expense of patient safety, it is quite unacceptable. There are publicly available documents which attest to Merck’s stalling on safety labelling requested by the FDA division responsible for approving new drugs. The FDA’s safety labelling requests were based on the evidence of clinical trials conducted by Merck and reported to the FDA. The manufacturer continued its direct-to-consumer advertising campaign with no mention of possible (sometimes fatal) cardiovascular side-effects. We patients are not able to know of the potential for adverse reactions to a drug when such information is suppressed, and we are thankful that there is someone who is sufficiently brave and sufficiently informed to care for our interests.
Mr Smith
Here is what your concern over Dr. Graham's six children demonstrates. His
right to have six kids is not unlike our right not to die from the drugs sold to resolve pain. To listen to you, 10,000
deaths attributed to Vioxx would be OK.
But the molecular mechanism is actually
cellular in nature. Molecular mechanisms are not organic biology which is what occurs within the cells.
Doctors can still prescribe Vioxx under
black label but what our research has shown is organic sulfur ( pure MSM ) may be more effective not only for the pain but also for the cellular regeneration necessary for cartilage regeneration and
repair of the nerve endings.
Why have you not responded to Daniel
Graham who spoke eloquently in defense of his father. Sir I believe you need
to explain what expertise you have that
makes you think any of us care to listen
to someone who feels that mortality data is just another solution to the over
population question.
Graham was not the first to point out Vioxx problems
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tagged as:
- solution
Google; Vioxx Timeline NPR... this will show you part of the horrible # of deaths and injuries suffered by people taking Vioxx, a drug that Merck still defends to this day as safe and effective. After you have done the research on Merck and Vioxx, remember this... They are promoting Gardasil the same way, bribing, lying and manipulating, to get at our health insurance dollars and trying to convince the Feds to REQUIRE Gardasil, not only for girls, but boys and men are on Merck's target list.
Eric Topol and Steven Nissen of the Cleveland Clinic reported in JAMA in 2000 that Vioxx was killing people. They let Merck know before they published, and Merck's reaction was to send Alise Reicin (Merck scientist then, executive now) down to first try to get them to change their paper, second, threaten them professionally if they published.
They published, Merck tried to screw them professionally, but they continued to work at Cleveland Clinic through 2005 when they exposed ANOTHER Merck drug, Pargluva, also killing people, this time they caught it in trials. Their research and (this time) persistance stopped that drug before it was released. The FDA was getting ready to release Pargluva after it passed the last FDA panel's approval.
With Vioxx Merck submitted to the FDA the correct data with the wrong conclusion (Vioxx was safe). When they published in New England Journal of Medicine, they gave the editors incomplete data so that their conclusions of safety were supported by it. Big Pharma knows the FDA will not look, they submit the correct data to the FDA because it is required by law. No such law protects the consumer or the medical magazines from submission of false data.
NEJM editor Dr. Drazen would later accuse Merck of hoodwinking the journal and demanded a correction from Merck in 2005. They're still waiting.
In Australian lawsuits against Merck and Vioxx LOTS of really bad info is coming out about Merck and the world of Big Pharma. One of the most fightening and potentially harmful was Elsevier (world famous publisher of scientific/medical journals) admitting in court records that Merck paid them to have a fake journal published. In this journal, content completely created by Merck, Merck pushed its drugs, including Vioxx. Elsevier admitted to creating 8 other fake journals, with 13 more in the works. they have since claimed that all such publications are stopped, or plans to publish abandonned.
Recently in Massachusetts (Sept 2009), a federal grand jury was commissioned to look into Vioxx, what Merck knew and when it knew as it contemplates charges against the company and individuals. Muder or manslaughter would be appropriate...
What would it take to get honest people with integrity in charge of public offices like the CDC, FDA, EPA? That problem would be solved if we the people started getting smart about this issue and demanding more from our President and the lawmakers who appoint and approve the regulatory agency leaders. Until that happens we can expect more of the same as good people like Steven Nissen, Eric Topol and David Graham are pressured to "shut up" while they are trying to protect the public interest.
FDA
It is completely ludicrous that it should be necesary to have someone inside the FDA alerting the world to the dangers of the drugs they approve! Hello? It is the JOB of the FDA to ensure that dangerous drugs are not sold at all! The situation os so bad, at this time, that anything which is approved by the FDA is suspect. I am much les likely to use it. I have to ask why it was approved - maybe because it is overpriced and the agency is getting a kickback from the outrageous profits? Maybe because the FDA is a progressive entity that wishes to contribute to population control by poisoning people with "FDA approved" drugs?
