Seven weeks before Merck pulled Vioxx off the market, a Food and Drug Administration medical safety officer presented warnings to his bosses that the drug increased the risk of heart attacks.
But the author of that study, Dr. David Graham, reportedly has told Senate investigators that he was pressured by FDA management to water down his conclusions after he told the agency of them on Aug. 11.
Graham is the associate director for science in the FDA's Office of Drug Safety. His study, done in conjunction with Kaiser Permanente, looked at records for 1.4 million patients. Nearly 30,000 of those patients had taken Vioxx. The study concluded there was a threefold risk of heart attacks and sudden death with high doses of the drug, as compared to those taking a competitor's drug, Celebrex.
Sources told ABC News that Graham, who was to publicly present his findings at a conference in France, wanted to conclude with a very clear warning stating that "high doses of Vioxx should not be prescribed or used."
But the head of the office that had approved Vioxx wanted the language softened because, he said, the FDA was not looking to change its position on Vioxx.
He wrote in an Aug. 13 e-mail, "I think this is pretty strong language since to my knowledge the FDA is not contemplating such a warning for labeling."
Graham, who spoke to investigators from Sen. Chuck Grassley's office, told them that he was "ostracized, subjected to veiled threats and intimidation," according to a statement from Grassley's office.
Ultimately under pressure from his superiors, he did rewrite the conclusion. Instead of saying, "High doses of Vioxx should not be prescribed or used," he changed the wording to, "This and other studies cast serious doubt on the safety of Vioxx greater than 25 milligrams per day."
In an e-mail, Graham told his superior, "I've gone about as far as I can without compromising my deeply held conclusions about this safety question."
A top official in the FDA office of drug safety wanted to make sure Vioxx manufacturer Merck received advance notice of the FDA study. In an e-mail on Aug. 12, she wrote, "However the study is presented, the manufacturer needs to know before it becomes public so that they can be prepared for the extensive media attention that this will likely provoke."
Grassley, R-Iowa, wants a full investigation of the FDA's handling of Vioxx. "It does raise questions about the FDA and their relationship with the company, as opposed to their number one goal, their only goal, let's say, of protecting the public health and safety," he told ABC News.
‘Standard FDA Review Process’
When asked about the pressure to change Graham's presentation, the FDA released this statement: "As a scientific agency, FDA values open discussion and frank exchange about scientific and medical issues. Dr. Graham discussed with his supervisor the abstract of a poster about Vioxx he presented last August in France. Such a discussion is part of the standard FDA review process for this type of abstract.
"After that discussion, it was Dr. Graham's decision to revise the abstract. He did so voluntarily and presented the abstract during a scientific meeting. He transmitted his completed report to his agency supervisors on Sept. 30. The standard agency review process for this type of report is a more rigorous scientific peer review."
Grassley, however, likened the FDA's handling of Vioxx to the controversy over the FDA's treatment of the use of anti-depressants in children. In that case, another FDA scientist who raised an alarm about the anti-depressants was prohibited from presenting his findings at an FDA advisory committee meeting.
Graham did present his findings at the conference in France, and just last week he delivered his final report to the FDA. In that final report he estimated that, given the 20 million Americans who had taken Vioxx, it was likely that there had been more than 27,000 cases of heart attacks and sudden cardiac deaths associated with the drug.
But despite the strong warnings from their own scientist, it was not the FDA, but Merck, the maker of Vioxx, who ultimately removed the drug from the market.