At FDA, Graham is still the whistle-blower – USA Today

Thu, 17 Nov 2005

On Nov. 18, 2004, Dr. David Graham, FDA’s associate director for science and medicine, blew the whistle in testimony before the Senate Finance Committee, on FDA’s “profound regulatory failure” to protect the public against lethal prescription drugs. See:Testimony http://finance.senate.gov/hearings/testimony/2004test/111804dgtest.pdf

One year later, Dr. Graham told USA Today:

“Today, the United States of America is worse off when it comes to drug safety than it was a year ago when I testified. That’s because the FDA’s recent drug safety initiatives serve only as window dressing, diverting attention away from real solutions, such as an independent Office of Drug Safety.”

Among the most harmful marketed drugs are the so-called atypical antipsychotics which are were approved for schizophrenia but are being prescribed primarily off-label, mostly to control behavior in children and the elderly– despite the fact that they are linked to severe, irreversible harm, including hyperglycemia, diabetes, and death. Dr. Graham says “FDA has known about this for two or three years.” He estimates that off-label use of antipsychotics may cause up to 62,000 excess deaths a year.

“What does FDA do? It tinkers with the label.”

USA Today reports that an article in this week’s Journal of the American Medical Association supports Graham’s assessment of the FDA.

Especially in the past five years, writes Howard Markel, a University of Michigan pediatrician and history of medicine professor, the FDA has been heading downward “from a sterling – albeit very human – regulatory agency into one much more tarnished, politicized, and increasingly disputed by the very people it was designed to protect.”

Clearly, news reports that essentially transcribed the self-serving claims made by high ranking FDA officials about the improvements in the agency’s safety standards were simply tripe. Reporters covering science, medicine, and healthcare agencies must be better trained to get at the truth by asking probing questions rather than transcribing what officials tell them. As the New York Times learned the hard way, a reporter’s reliance on government “sources” for “scoops” has resulted in the newspaper becoming a conduit for relaying planted misinformation.

Contact: Vera Hassner Sharav
212-595-8974

http://www.usatoday.com/news/health/2005-11-16-fda_x.htm     

USA TODAY
At FDA, Graham is still the whistle-blower
By Rita Rubin,

OLNEY, Md. – As David Graham sipped a large decaf skim mocha – hold the foam and whipped cream – at a suburban Washington, D.C., coffee shop last week, a fellow customer, a stranger, walked over and wished him well.

It was a year ago Friday that Graham made headlines by blowing the whistle on the Food and Drug Administration at a Senate committee hearing. But he’s still sometimes recognized by fans. (Related story: Graham’s least-favored drugs)

They’ll be happy to know that he’s still associate director for science and medicine in the FDA’s Office of Drug Safety, which – much to his dismay – is still part of the FDA center that reviews and approves new drugs.

But they may not be thrilled to hear what he has to say about what has changed – or, more accurately, what has not changed – since he told the Senate Finance Committee the FDA is “virtually defenseless” against another “terrible tragedy and a profound regulatory failure” like Vioxx. Merck pulled the blockbuster arthritis drug off the market in September 2004 because it raises heart attack and stroke risk.

“Today, the United States of America is worse off when it comes to drug safety than it was a year ago when I testified,” Graham says. That’s because the FDA’s recent drug safety initiatives serve only as window dressing, diverting attention away from real solutions, such as an independent Office of Drug Safety, Graham says.

Take the Drug Safety Oversight Board established by the FDA in February to oversee management of drug safety issues. “A kangaroo court,” Graham says, noting that several of the 15 members are FDA employees who work for the center that reviews and approves new drugs.

Or take the ongoing Institute of Medicine study of drug safety requested by the FDA. Graham says he doubts the study will make much of a difference, because it’s based largely on information supplied by the FDA.

Senate Finance Committee chair Chuck Grassley, R-Iowa, who convened the November 2004 hearing, says Graham should not be discouraged. “Dr. Graham and people like him make a big difference,” Grassley says.

Because of Graham’s coming forward, Grassley says, his staff talks to several FDA whistle-blowers – some new, some not – every week.

Neither Acting FDA Commissioner Andrew von Eschenbach nor Steven Galson, director of the FDA’s Center for Drug Evaluation and Research, agreed to be interviewed for this story.

Instead, Susan Bro, senior communications adviser in the FDA commissioner’s office, responded via e-mail:

“Who’s the ‘we’ behind the FDA? Thousands of cutting-edge scientists, physicians, pharmacists and public health experts who consult with their colleagues and outside experts to make sound medical decisions and recommendations each and every day. To characterize the work being done here as anything less than substantial, forward-looking and ambitious is simply not accurate.”

An article in this week’s Journal of the American Medical Association supports Graham’s assessment of the FDA. Especially in the past five years, writes Howard Markel, a University of Michigan pediatrician and history of medicine professor, the FDA has been heading downward “from a sterling – albeit very human – regulatory agency into one much more tarnished, politicized, and increasingly disputed by the very people it was designed to protect.”

http://www.usatoday.com/news/health/2005-11-16-fda-side_x.htm
Drugs non- grata
By Rita Rubin, USA TODAY

At a Senate hearing a year ago, FDA whistle-blower David Graham named five drugs he felt posed serious safety concerns:

Accutane

Graham called this acne drug a “regulatory failure” because the FDA had not done enough to ensure that pregnant women, in whom it can cause serious fetal abnormalities, not take it. Less than a week later, the FDA announced plans to strengthen such efforts.

Bextra

Pfizer stopped selling Bextra, a cousin of Vioxx and Celebrex, on April 7. The FDA said it wanted Bextra withdrawn because it was no better than Celebrex and was more likely to cause a deadly skin reaction. Graham says the FDA knew this before approval.

Crestor

Graham said Crestor is the only cholesterol-lowering drug that causes acute kidney failure. “I think Crestor should be a second-line drug,” Graham says. Maker AstraZeneca reported Tuesday at a scientific meeting that Crestor, alone or with cholesterol drug Zetia, is “an important and effective treatment option” for severe high cholesterol.

Meridia

Graham said this weight-loss drug can cause high blood pressure. But in August, the FDA denied a petition from consumer advocacy group Public Citizen to withdraw it. The agency said Meridia’s benefits outweigh its risks.

Serevent

An FDA advisory committee in July recommended that Serevent and two other asthma drugs stay on the market. But the panel urged more research to see whether the drugs might worsen asthma in some.

In an interview last week, Graham talked about a new set of drugs he’s concerned about:

Atypical anti-psychotics

Risperidone, or Risperdal, is the oldest and likely best known of the drugs approved to treat schizophrenia. But they’re widely used off-label for behavioral problems in elderly dementia patients.

In April, the FDA warned that off-label use has been linked to a higher death risk, and it asked makers to add to their labels a black-box warning noting the risk and that treating behavioral problems in dementia patients is an unapproved use.

“FDA has known about this for two or three years,” Graham says, figuring that off-label use may cause up to 62,000 excess deaths a year. “What does FDA do? It tinkers with the label.”

Natrecor

In 2001, the FDA followed its advisory panel’s advice and approved Natrecor to treat hospitalized heart failure patients.

Graham cites a July New England Journal of Medicine article by Eric Topol of the Cleveland Clinic that questions whether the drug should stay on the market, given that no trial has yet proved that it reduces the risk of death or repeated hospitalization from heart failure. Last month, maker Scios posted a letter on its site saying Natrecor is safe and effective when used in hospitalized heart failure patients.

Pargluva

Unlike other drugs that concern Graham, this type 2 diabetes pill isn’t yet on the market, but he cites its recent history as another example of FDA laxity on safety. An advisory panel Sept. 9 voted 8-1 in favor of approval. Collaborators Bristol-Myers Squibb and Merck said Oct. 18 they’d received an “approvable letter” from the FDA that it would OK Pargluva once questions about ongoing and finished studies were answered.

But on Oct. 20, The Journal of the American Medical Association website posted a critical analysis of the same data reviewed by FDA staff and the advisory panel. Compared with a placebo or the diabetes drug Actos, Pargluva raised the risk of death, heart attack, stroke and congestive heart failure, the authors wrote.

On Oct. 27, Bristol-Myers said it might do more studies, or it might just stop developing Pargluva.

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