A Food and Drug Administration official who sought to estimate the harm done to patients by side effects of the painkiller Vioxx said yesterday that his supervisors tried to suppress his conclusions, according to Sen. Charles Grassley (R-Iowa).
Grassley said in a news release that David Graham, associate science director of the Office of Drug Safety, told him that agency officials "ostracized" him and subjected him to "veiled threats" as he tried to have his study cleared for publication. When a top FDA official suggested "watering down" the report, Graham responded in an e-mail: "I've gone about as far as I can without compromising my deeply-held conclusions about this safety question."
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Graham gave Grassley a copy of an e-mail in which another top official wrote that Merck & Co., which made Vioxx, "needs to know before it becomes public so they can be prepared for extensive media attention that this will likely provoke." Merck decided to pull Vioxx from the market last week after a major clinical trial, unrelated to the FDA review, indicated the drug was causing an increased risk of heart attacks and strokes.
Steven Galson, acting director of the FDA's drug center, called Graham's accusations, as relayed by Grassley, "baloney." He said that Graham's study was going through the same review process used for all major drug-safety issues, and that the agency was frustrated by Graham's inability to produce the data he promised. "There was no battle because there was no data," Galson said. "We were waiting all summer, but he missed his deadline."
Graham's analysis was based on a review of 1.4 million Kaiser Permanente patients given Vioxx or one of its competitors, Celebrex. In a limited presentation at a conference in France this summer, Graham said the data showed that more than 27,000 heart attacks and sudden cardiac deaths would have been avoided if the patients had used Celebrex rather than Vioxx.
Grassley, who as chairman of the Senate Finance Committee has initiated a series of reviews of controversial FDA decisions, said: "It seems that while Merck was taking a fresh look at its clinical data in search of trouble, the Food and Drug Administration was challenging its own researcher. 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.' "
Just after Merck announced that it would recall Vioxx, Galson said in a teleconference that the FDA had received only an abstract of Graham's work and was awaiting the data and full report.
In a statement yesterday, the FDA said that after discussing his abstract with agency officials, "it was Dr. Graham's decision to revise the abstract. . . . He transmitted his completed report to his agency supervisors on September 30. The standard agency review process for this type of report is a more rigorous scientific peer review."
Grassley, however, likened Graham's experience to that of another FDA scientist, Andrew D. Mosholder, who had conflicts with his superiors this year over antidepressants and suicide in young people.