Juicy news: Scientist says FDA called journal to block Vioxx article

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Posted 11/28/2004 11:41 PM

http://www.usatoday.com/news/health/2004-11-28-fda-vioxx_x.htm

 

Scientist says FDA called journal to block Vioxx article

By Rita Rubin, USA TODAY

 

Just days before a medical journal was to publish a Food and Drug

Administration-sponsored study that raised concerns about the safety of

the arthritis drug Vioxx, an FDA official took the unusual step of

calling the editor to raise questions about the findings' scientific

integrity, suggests e-mail obtained by USA TODAY.

 

Lead author David Graham says the call was part of an effort to block

publication of his research, an analysis of a database of 1.4 million

Kaiser Permanente members showing that those who took Vioxx were more

likely to suffer a heart attack or sudden cardiac death than those who

took Celebrex, Vioxx's rival. Graham had reported his study in August at

an epidemiology meeting in France, but publication in a medical journal

would have exposed it to a wider audience.

 

Graham, associate director for science and medicine at the FDA's Office

of Drug Safety, says The Lancet, a medical journal published in London,

had planned to post the study on its Web site Nov. 17, a day in advance

of his appearance before the Senate Finance Committee to testify about

the FDA's handling of Vioxx.

 

Merck had pulled the drug from the market Sept. 30 because of safety

concerns. Publication of the study could have embarrassed the FDA, which

was being criticized for not warning patients sooner of Vioxx's

cardiovascular risks.

 

Steven Galson, acting director of the FDA's Center for Drug Evaluation

and Research, said Sunday that Graham's charges are unfounded. " We

didn't make any efforts to block publication in The Lancet, " he said.

" What we did is let The Lancet know that the paper was submitted in

violation of the agency's clearance process. " Graham had sought to

publish his study before getting the FDA's OK, Galson said.

 

And in a written statement, FDA Acting Commissioner Lester Crawford said

that Galson contacted Lancet editor Richard Horton " out of respect for

the scientific review process. "

 

Galson said he would like to see the paper published some day but didn't

see the value of timing its release to the Senate hearing, " not exactly

a scientific imperative. "

 

Graham says he pulled his paper at the last minute because he feared for

his job. Following is a chronology of the events surrounding the paper's

withdrawal:

 

• Nov. 12. Galson called Horton to tell him that the FDA had not cleared

Graham's paper for publication. He then e-mailed Horton a link to a

document describing the FDA's internal review process for journal

articles. " As you will see, there are some ambiguities here, " Galson

said in his e-mail.

 

In a later e-mail to Horton that day, Galson brought up points from a

nine-page review of Graham's study by Ann Trontell, deputy director of

the FDA's drug safety office. Galson and Trontell noted discrepancies

between the article submitted to The Lancet and an abstract of the study

that had been submitted in May for presentation at a second scientific

meeting, an American College of Rheumatology conference. Trontell's

review, which Graham had forwarded to Horton, refers to " potential

charges of data manipulation. "

 

Graham says he had already explained the discrepancies to his superiors

at the FDA. After the abstract was submitted to the rheumatology group,

Graham says, he discovered two problems: A computer program had

misclassified the amount of Vioxx some patients had taken; and one of

his co-authors noticed that an analysis Graham had done was incorrect.

 

Graham says the rheumatology group told him that it was too late to

correct the printed abstract, but that he could present the corrected

analysis at its annual meeting in October, as he had at the epidemiology

meeting in August.

 

• Nov. 14. In an e-mail to Galson, Horton wrote, " You will not be

surprised if I say that I was a little taken aback to get your call on

Friday (Nov. 12). " It is very unusual indeed for a member of the

employing institution of an author to contact us in the middle of the

review and publication process of a manuscript. "

 

Horton wrote that Galson's call could be perceived as an improper

attempt to interfere with The Lancet's review process. Raising the

possibility that a scientist manipulated data " is an extremely serious

allegation, " Horton wrote. " One could read such an allegation as an

attempt to introduce doubt into our minds about the honesty of the

authors — doubt that might be sufficient to delay or stop publication of

research that was clearly of serious public interest. "

 

• Nov. 18. Graham told a Senate panel that the FDA is " virtually

defenseless " against another " terrible tragedy and a profound regulatory

failure " like Vioxx.