A sick agency in need of a cure? - FDA - USNews

[Guest guest]

{Should citizens persist in the unfounded belief that the FDA serves the

interests of US citizenry? Alternatively, should we willingingly accept

that the primary duty of " regulatory " agencies, the CDC, and IOM is to

the owners and investors who control major pharmcos?

,

who believes that insights accumulating in the various FDA

articles help us move towards solutions, including (someday soon) a

major media's expose of the CDC's 1999 thimerosal findings and the CDC's

deliberate data-dilutions regarding thimerosal's adverse effects. The

coverup must end soon. Helpful urls follow the news item.}

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A sick agency in need of a cure?

Recall of a popular pain drug has focused attention on government drug

regulation

By Spake

http://www.usnews.com/usnews/issue/041213/health/13fda.htm

When Graham got his medical degree from s Hopkins University,

he figured he'd opt for the comforts of an academic career in neurology.

But he couldn't shake his other infatuation, with public health, so

instead of heading to the lab he began what would become a 20-year

government career at the U.S. Food and Drug Administration: " At the

FDA, " he says, " there seemed to be the possibility that you could have

an effect that would benefit patients to a greater extent than at any

university. "

Today, that dream has turned sour. Indeed, Graham is now at the center

of a national controversy over the FDA's ability to protect the public

against unsafe medicines. As associate director for science and medicine

in the FDA's Office of Drug Safety, Graham told Congress last month that

FDA's problems with ensuring drug safety were " immense in scope " and

left the nation " virtually defenseless " against the chance that unsafe

drugs will reach consumers.

Graham was called before the Senate Finance Committee to explain why it

took the FDA years to acknowlege that the pain reliever Vioxx increased

cardiovascular risks. Merck, Vioxx's manufacturer, removed the drug from

the market in September because of Vioxx-related heart attacks and

stroke, which Graham and other researchers say may surpass 100,000 in

the United States alone. The FDA has known of the risks since 1999, yet

a warning was not added to the drug's label, which the FDA regulates,

until 2002. According to Kweder, the deputy director of the

Office of New Drugs, the FDA did not have enough leverage to force Merck

to include a warning about heart risks; the agency negotiated with the

company for some 14 months after the problem was first identified. When

the warning was included, it was not a " black box " type, which might

have reduced the flood of advertising directed at consumers. Vioxx

remained a top seller for two more years.

High stakes. Product liability lawsuits, according to Merrill Lynch, may

run as high as $18 billion, from patients and their families. And last

week the New York State pension fund announced it was suing Merck,

charging that the company concealed Vioxx's risks from shareholders,

leading to a loss of $171 million by the fund. " Vioxx is a terrible

tragedy and a profound regulatory failure, " Graham told the Senate

committee. It illustrates troubles at the FDA " that will make future

Vioxxes inevitable. " Graham, who is expressing his opinion, not that of

the FDA, paints a picture of " an agency in denial, " where bureaucratic

wrangling has replaced scientific debate and a climate of fear stifles

healthy dissent.

Many scientists believe that FDA's dual role of promoter and regulator

of medicines is to blame. " The people in the agency who become the

champion of a new drug can't be responsible for sustained surveillance, "

says Topol, chairman of cardiovascular medicine at the Cleveland

Clinic. " The position is just too awkward, and if they are critical of a

drug, it makes them look like they made the wrong decision in the first

place. " As a member of the Institute of Medicine, Topol may serve on the

committee the IOM is impaneling at the request of the FDA to sort out

its drug surveillance system and make recommendations. " I believe the

FDA is really trying to do the right thing, " says Topol, " but they need

more authority over the companies. "

Part of the problem is that drug companies pay " user fees " to make up a

portion of the FDA's costs for reviewing and approving drugs. Indeed,

user fees now pay the salaries of about half of the more than 1,400

doctors, pharmacists, chemists, and other scientific personnel who

decide if a new drug is safe and effective, according to a government

report issued last year. This measure, first passed in 1992, was

intended to provide the FDA with greater resources to reduce the time

needed to evaluate new drugs, and it has. Where a new drug approval

commonly took 27 months in 1993, it took 14 months in 2001. Ten months

is now the goal.

" There's not a problem with speeding up the approval process, " says

Bruce Psaty, a drug safety expert at the University of Washington. " It

just requires an additional commitment to drug safety. And that hasn't

happened. It's like building up one set of muscles and ignoring the

other. " As the approval time has become shorter, the number of recently

approved drugs withdrawn from the market has grown threefold.

Psaty feels this is one of many signs that more resources need to go

into post-marketing surveillance of drugs, which is now limited

primarily to self-reporting by physicians and drug companies (box, Page

36). Psaty reviewed the FDA documents on both Vioxx and Baycol, an

ill-fated cholesterol-lowering statin that caused cases of muscle

injury, kidney failure, and death. " The medical reviewers for FDA raised

the correct issues, " he says. " But what happens to these issues after

they are raised? "

No one seems to have an answer, including the reviewers themselves. In a

survey released last year by the Department of Health and Human

Services' inspector general, 66 percent of FDA medical reviewers said

they were somewhat or not at all confident that the FDA adequately

monitors the safety of drugs once they are on the market. The same

report found that out of some 2,400 post-marketing studies reviewers had

asked companies to conduct, only 882 had been done.

What's more, some 40 percent of reviewers interviewed said that the

review process had gotten worse in terms of allowing time for in-depth,

science-based reviews. About a fifth said the work environment did not

allow for the expression of differing scientific opinions, and 18

percent said they had felt pressure to approve or recommend approval of

drugs, despite reservations about safety or effectiveness.

Graham believes part of the problem is philosophical. The pressure to

approve drugs comes from the agency's position that potential for harm

must be proven beyond doubt. When Vioxx was approved, the FDA medical

reviewer questioned the drug's potential for risky clotting but said the

agency could not answer " with complete certainty " whether the drug would

lead to cardiovascular events. This demand for " complete certainty " that

a drug is unsafe " is the heart of the scientific problem at FDA, " says

Graham.

This attitude leads to the approval of questionable drugs, which

according to Graham include: Accutane, a potent acne drug that can cause

birth defects; Crestor, a statin that has been associated with the same

muscle-wasting disorder as Baycol, as well as kidney failure; and

Bextra, like Vioxx another painkiller in the -2 inhibitor class,

which may increase cardiovascular risks in some people.

The first product liability lawsuit against Bextra was filed last month

in New York. , a 46-year-old New Jersey waste disposal

driver who had taken Bextra for nine months for arthritis pain, suffered

a heart attack in June and died in his sleep. His widow sued. If the

case goes to trial, part of the evidence may be the research of Garret

FitzGerald, the first scientist to suggest that -2's might harm the

heart. FitzGerald has identified one possible mechanism: The drugs

suppress a protective lipid, which in turn leads to more clotting,

increased blood pressure, and hardening of the arteries.

Palace intrigue. The FDA has scheduled a meeting in February to discuss

these drugs. Curt Furberg, a colleague of FitzGerald and an FDA drug

safety adviser, was originally invited to attend this meeting. " Then, I

had a call from one of the administrators of the committee, and she said

that I'd been disinvited because of statements I'd made in the New York

Times, " he says. Furberg had expressed the opinion that Pfizer was

trying to suppress the results of studies about Bextra.

A few days later, Furberg got a call from someone on the FDA's Ethics

Committee who apologized, said that acting Commissioner Lester Crawford

had not been informed of the disinvitation, and asked for a confidential

copy of Furberg's draft manuscript about Bextra, which he provided. He's

heard nothing more.

The FDA's Kweder insists that the agency is not trying to stifle

scientific dissent and that she assumed Furberg's disinvitation had gone

through Crawford's office. It hadn't.

So will Furberg be reinvited? Kweder hesitated: " No decision has been

reached. "

Long overdue. When the new Congress convenes in January, Sen.

Grassley plans to introduce legislation to establish an independent drug

safety office, separate from the FDA, that will monitor safety,

negotiate labeling changes, oversee post-market testing, and more. The

Journal of the American Medical Association supported a separate drug

safety agency this month. " My sense is now we have the momentum, " says

Furberg. Many scientists feel it's long overdue.

But the FDA opposes such an office as unnecessary. " I don't think there

is a conflict of interest, " says Kweder. " The decisions about safety and

risk always have to be considered fully. " She also believes that the FDA

fosters a free-flowing exchange of ideas about drug safety: " We thrive

on disagreements. "

Three years ago, with FDA's support, Graham embarked on a large study of

the heart risks associated with Vioxx in 1.4 million patients at Kaiser

Permanente in California. Completed in September, just before Merck

withdrew the drug, the study showed a more than threefold increase in

serious cardiovascular events among some Vioxx patients. The study was

accepted for publication by the Lancet , a highly regarded medical

journal. Last week, it became public that FDA officials contacted the

Lancet 's editor to complain about the study's " basic data integrity. "

The Lancet was not intimidated, but Graham decided to withdraw his study

from the journal anyway. " Basically, I was threatened with punitive

action, " he says. " The article was censored. "

*

Reporters and editors are attuned to this subject. They need hear about

the CDC's 1999 findings of a strong association between thimerosal and a

range of neurologic disorders including autism and about the CDC's

subsequent and deliberate dilutions of the its own data (1-2). Reporters

and editors also need hear about the Institute of Medicine's deliberate

focusing upon studies strongly tainted by conflict of interest regarding

thimerosal (3). Anyone with a working relationship with a reporter is

invited and encouraged to share with them these three URLs.

-

CDC thimerosal findings in 1999 - subsequent data dilution - Generation

Zero analysis is up on Safe Minds web-site

1. text synopsis

http://www.safeminds.org/Generation%20Zero%20Syn.pdf

2. full analysis, with charts

http://www.safeminds.org/Generation%20Zero%20Pres.pdf

Conflicts of interest in various studies that whitewashed thimerosal.

3. Mercury in Medicine Panel Discussion

Auburn University

Mark Blaxill - Powerpoint Presentation

<http://www.nationalautismassociation.org/mercury/Mark%20Blaxill.ppt>

* * * * * * *

Regulation redefined:

At F.D.A., Strong Drug Ties and Less Monitoring

By GARDINER HARRIS

http://www.nytimes.com/2004/12/06/health/06fda.html

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