FDA Officials Tried to tone Down Report of 27,000 heart attacks on Vioxx – WSJ – WashPost

FDA Officials Tried to tone Down Report of 27,000 heart attacks on Vioxx – WSJ – WashPost

Sun, 10 Oct 2004

The FDA attempted to block a senior medical officer from making his findings known about the lethal hazards of Vioxx: Senator Chuck Grassley stated: “Instead of acting as a public watchdog, the Food and Drug Administration was busy challenging its own expert.”

Dr. David Graham, associate science director of the Office of Drug Safety, analyzed the data of 1.4 million Kaiser Permanente patients given Vioxx or one of its competitors, Celebrex. He found 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.

Based on the evidence, Dr. Graham concluded that “this and other studies cast serious doubt on the safety of rofecoxib (Vioxx)” at doses greater than 25 milligrams “and its use by physicians and patients.”

According to the Wall Street Journal and the Washington Post, senior FDA officials wanted him to water down his conclusion, subjecting him to “veiled threats” when he stood firm.

FDA officials tried to forestall public disclosure about the increased risk of heart attacks–even as Merck was in the process of deciding to pull Vioxx off the market.

Contact: Vera Hassner Sharav
212-595-8974

http://www.washingtonpost.com/wp-dyn/articles/A16546-2004Oct7.html

FDA Official Alleges Pressure to Suppress Vioxx Findings

By Marc Kaufman
Washington Post Staff Writer
Friday, October 8, 2004; Page A23

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.”

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.

http://online.wsj.com/article/0,,SB109719486136740053,00.html
THE WALL STREET JOURNAL
October 8, 2004

FDA Officials Tried To Tone Down Report on Vioxx
By ANNA WILDE MATHEWS
October 8, 2004; Page B2

The Food and Drug Administration staffer whose research pointed to the cardiovascular risks of Vioxx in August clashed with superiors at the agency who felt his conclusions about the drug’s safety were too strongly worded. E-mail messages detailing disagreements between the researcher, David Graham, and other FDA officials emerged in the wake of last week’s decision by Merck & Co. to recall the blockbuster arthritis drug because of concerns that it was tied to heart attacks and strokes. The messages were reviewed by The Wall Street Journal.

Congressional scrutiny has focused on how the FDA responds to safety issues raised by its own staffers. Senate Finance Committee Chairman Charles E. Grassley (R., Iowa) is one of several lawmakers investigating the FDA’s handling of safety. “Instead of acting as a public watchdog, the Food and Drug Administration was busy challenging its own expert,” Sen. Grassley said in a statement.

Steven Galson, acting director of the FDA’s drug center, yesterday said that “all there was was an exchange of views, which is completely regular and normal.” Dr. Graham did change his conclusions slightly “on his own,” he said, but the adjustment didn’t “change the thrust of the report.” Dr. Graham’s research, done with several authors, focused on Vioxx, generically called rofecoxib, and similar drugs. The research found high doses of Vioxx correlated with risk of a heart attack or sudden cardiac death.

Some of the findings became public Aug. 25, when an abstract was presented at a medical conference. On Aug. 12, Anne Trontell, an official in the FDA drug-safety office, wrote in an e-mail to another official that a recommendation about high-dose Vioxx was “unnecessary and particularly problematic” because the FDA funded the study, and that Dr. Graham might be asked to also display “alternative FDA opinion on this.”

On Aug. 13, John Jenkins, director of the FDA’s office of new drugs, wrote about a proposed conclusion that “this is pretty strong language since to my knowledge FDA is not contemplating such a warning for labeling.” He added, “I think something like, ‘this and other studies suggest an increased risk of AMI [acute myocardial infarction, or heart attack] with rofecoxib use and should be considered by prescribers when making individual treatment decisions.’ ”

Dr. Graham wrote the same day that he had “gone about as far as I can without compromising my deeply-held conclusions about this safety question.” In the end, the conclusions listed in the Aug. 25 abstract were more toughly worded than Dr. Jenkins appeared to favor. The abstract said “this and other studies cast serious doubt on the safety of rofecoxib” at doses greater than 25 milligrams “and its use by physicians and patients.”

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