FDA Tried To Thwart Release of Vioxx Data
Researcher sought to voice safety fearsOct 8, 2004 | Star Ledger
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A Food and Drug Administration researcher was pressured by agency officials who wanted to prevent him from publishing a study that linked painkiller Vioxx to a high rate of heart problems, congressional investigators said yesterday.
For the past few months, FDA epidemiologist David Graham was subjected to "veiled threats and intimidation" about his efforts to release his findings, according to U.S. Sen. Charles Grassley (R-Iowa), who heads the Senate Finance Committee.
Vioxx was pulled from the market last week by Merck, which cited data showing an unexpectedly high rate of heart problems. Graham reviewed medical records from 1.4 million people and reportedly projected Vioxx may have led to more than 27,000 heart attacks and strokes.
A series of e-mails released late yesterday by the committee revealed Graham's supervisor suggested alerting Merck to the findings, shortly before Graham presented the data at a scientific conference in France two months ago. The official wrote Merck "needs to know before it becomes public, so they can be prepared for extensive media attention that this will likely provoke."
Grassley said: "While Merck was taking a fresh look at its clinical data in search of trouble, the FDA was challenging its own researcher. Instead of acting as a public watchdog, the FDA was calling his (Graham's) work scientific rumor."
In a statement, the FDA said "discussion is part of the standard FDA review process," which includes pursuing a "more rigorous scientific peer review." The agency also said it values "open and frank discussions about scientific and medical issues."
This marks the second time this year the FDA has been accused of trying to squelch the findings of one of its medical researchers. In both cases, the researchers were examining safety concerns about widely used prescription medicines.
At an FDA meeting last February, the agency prevented a researcher from presenting his conclusions that antidepressants were linked to suicide in children and adolescents. At the time, FDA officials said the researcher's findings merited more extensive review.
The episode prompted two congressional committees to launch investigations. The committees are looking at how the agency handles clinical trial data and responds to reports of serious side effects, among other things.
"In both cases, what looks like foot-dragging by the FDA is downright alarming," Grassley said.
The Graham study was initiated by Kaiser Permanente in 2002. The health maintenance organization wanted to examine risks associated with Vioxx, which was widely promoted.
Kaiser officials sought out Graham and also contacted the FDA, which initially provided about $50,000 in seed money. Graham worked with Kaiser officials and Wayne Ray, a Vanderbilt University medical school professor on the project.
Initially, FDA officials were believed to be enthusiastic about the project, according to two people involved in the study. The effort involved sifting through Kaiser medical records and death certificates to find risk factors known to be tied to heart disease.
Agency enthusiasm, however, turned to anxiety last spring after the results were shared with FDA officials, who disagreed with Graham's conclusions, according to these people.
The study found Vioxx demonstrated a greater chance of causing heart attacks and sudden cardiac death than Celebrex, a rival drug made by New York-based Pfizer. And the highest dosages of Vioxx caused three times the risk of heart problems as nonsteroidal anti-inflammatories.
As a result, the agency attempted to "water down" the findings, Grassley said.
In response to an e-mail from a supervisor, Graham wrote back Aug. 13 that he had "gone about as far as I can without compromising my deeply held conclusions about this safety question" about Vioxx.
He ultimately presented the findings in France Aug. 25. But the study contained a disclaimer indicating the findings weren't necessarily those of the FDA. In effect, this amounted to a compromise that allowed Graham to present his findings, the people involved in the story said.
The FDA said Graham voluntarily revised his findings, although he still raised serious questions about the safety of Vioxx.
"Based upon the evidence in this study, I don't think doctors should prescribe high-dosage Vioxx, and patients shouldn't take it," Graham said at the time. "The problem is that some patients continue to take it for 30, 60 or 90 days."
At the time, Merck disagreed vehemently with the findings. But last week, Merck withdrew Vioxx after learning the painkiller caused twice as many heart attacks and strokes than a placebo, or dummy pill, in people who took the drug for more than 18 months.