FDA Accused of Silencing Vioxx Warnings

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Fri, 8 Oct 2004 07:45:14 -0400

[sSRI-Research] FDA Accused of Silencing Vioxx Warnings [and

let's not leave out SSRIs...]

 

 

 

FDA Accused of Silencing Vioxx Warnings

 

http://news./news?tmpl=story & cid=534 & u=/ap/20041008/ap_on_he_me/fda_vio\

xx_worries & printer=1

 

24 minutes ago

 

By DIEDTRA HENDERSON, AP Science Writer

 

WASHINGTON - The Food and Drug Administration (news - web sites) silenced

one of its drug experts who raised safety concerns weeks before Merck

& Co.

yanked the blockbuster drug Vioxx due to increased risks for heart attack

and strokes, the chairman of the Senate Finance Committee said Thursday.

 

Dr. David J. Graham, associate director for science in the FDA (news - web

sites) Drug Center's Office of Drug Safety, told Senate investigators he

faced stiff resistance within the regulatory agency to his findings.

" Dr. Graham described an environment where he was 'ostracized,' 'subjected

to veiled threats' and 'intimidation,' " Sen. Chuck Grassley, R-Iowa,

said in

a statement after Finance Committee investigators interviewed the

researcher

Thursday.

 

Graham told The Associated Press that Grassley's characterization was

accurate. Raising safety concerns within the agency is " extremely

difficult, " the 20-year employee said, declining further comment.

 

In a prepared statement, the FDA said it " values open discussion and frank

exchange about scientific and medical issues " and subjects its

scientists to

" more rigorous " scrutiny than typical scientific peer reviews. The

Government Accountability Office, an investigative arm of Congress,

already

has been asked to look into whether the FDA muzzled another staffer who

linked antidepressants to raising the odds of children suffering suicidal

tendencies. When Merck voluntarily pulled Vioxx from the market on

Sept. 30,

the GAO was asked to roll the FDA's handling of that controversy into its

inquiry.

 

That report is not expected for months. Grassley's committee is one of

three

in Congress also scrutinizing the FDA's actions.

 

A " picture is emerging of an agency that can't see the forest for the

trees, " Grassley said. " Merck knew it had trouble on its hands and took

action. At the same time, instead of acting as a public watchdog, the Food

and Drug Administration was busy challenging its own expert and

calling his

work 'scientific rumor.' "

Graham was lead author on a research project that studied the records of

1.39 million Kaiser Permanente patients, including 40,405 treated with

Pfizer's Celebrex and 26,748 treated with Vioxx. The study found that high

doses of Vioxx, known as rofecoxib, tripled risks of heart attacks and

sudden cardiac death.

The research team's original conclusion said that high doses of Vioxx

should

not be prescribed or used.

Graham, scheduled to present those findings in late August during an

epidemiology conference in France, said he ran into resistance when

the FDA

reviewed his abstract.

" I think the recommendation about high dose rofecoxib is unnecessary and

particularly problematic since FDA funded this study and David's travel to

France to present it, " Anne E. Trontell, deputy director of the FDA's

Office

of Drug Safety, wrote in an Aug. 12 e-mail.

The internal e-mail exchange was released by Grassley.

In the e-mail, Trontell suggested that Graham defer his presentation in

favor of a journal article so dissenting scientists - including within the

FDA - could comment.

She also said Merck should be alerted before the findings became

public " so

they can be prepared for extensive media attention that this will likely

provoke. "

Others within the agency suggested Graham's conclusion was too strongly

worded, given the FDA had not added such warnings to Vioxx labels.

 

" I've gone about as far as I can without compromising my deeply held

conclusions about this safety question, " Graham replied in an Aug. 13

e-mail.

 

The FDA said such discussions are typical before scientific findings are

published.

 

The conclusion Graham presented in France was revised: " This and other

studies cast serious doubt on the safety " of Vioxx doses higher than

25 mg.

per day.

 

The FDA said that Graham decided to revise his abstract conclusion.

" He did

so voluntarily, " the agency said.

 

In testimony before a congressional panel in mid-September, Andrew

Mosholder, an FDA epidemiologist, said his bosses asked him to soften

recommendations about antidepressants.

 

Mosholder's analysis pointed to increased suicidal thoughts and behaviors

among children taking antidepressants well before federal advisers pushed

for strident warnings on the drugs. He suggested preferential use of

Prozac,

the only drug approved to treat depressed children and - according to his

review - the one with the lowest risk.

 

His supervisors within the FDA told him to suggest that children use such

medications " with caution, " Mosholder told the Congressional panel.

 

Dr. Paul Seligman, acting director of the FDA's Office of Drug Safety,

said

the agency did not pressure Mosholder to change his conclusion.

___

On the Net:

FDA: http://www.fda.gov/