A drug manufacturer and the Food and Drug Administration failed the public by not heeding the warning signs associated with Vioxx, and Congress should investigate their actions, a Cleveland Clinic cardiologist said Wednesday.
And Dr. Eric Topol, chairman of the Clinic’s department of cardiovascular medicine, is not the only one who wants answers.
Last week, when Merck & Co. pulled Vioxx from the worldwide market after research showed the drug put patients at greater risk for heart attacks and strokes, Senate Finance Committee Chairman Charles Grassley of Iowa asked the FDA for detailed information.
Citing multiple studies in a letter to Health and Human Services Secretary Tommy Thompson and Acting FDA Commissioner Lester Crawford, Grassley asked: “Why has the FDA blindly dismissed a wealth of data showing serious cardiovascular side effects occurring in patients using Vioxx since the drug was approved in 1999?”
Though no decision has been made, it is also possible that the Government Accountability Office, the investigative arm of Congress, will include Vioxx in its investigation of the safety of drugs approved by the FDA.
Marcia Crosse, director of health care issues for the GAO, said House and Senate committees cited antidepressants as one issue of concern when they requested a broad inquiry, but did not limit it to specific drugs.
In an editorial posted Wednesday on the Web site of The New England Journal of Medicine more than two weeks before print publication, Topol wrote that “it is possible that there are tens of thousands of patients who have had major adverse events” attributable to Vioxx.
In calling for the congressional review, Topol wrote that officials from Merck and the FDA “share responsibility for not having taken appropriate action and not recognizing that they are accountable for the public health.”
Merck “valued sales over safety,” Topol said. Had it not, he wrote, “a suitable trial could have been initiated rapidly at a fraction of the cost of Merck’s direct-to-consumer advertising campaign.”
The campaign worked, since patients would regularly ask their doctors for Vioxx, saying, “I saw it on TV,” Topol said in an interview.
He faulted the FDA for allowing the advertising to continue in spite of concerns raised by independent investigators.
Vioxx, used to treat osteoarthritis, rheumatoid arthritis, menstrual pain and acute pain, had worldwide sales of $2.5 billion in 2003.
Merck said in a statement that Topol’s opinion is “flawed.” The company maintained that it told the FDA, researchers and the media about the cardiovascular concerns over Vioxx as soon as the risks were uncovered, beginning in 2000.
The company also noted that a randomized, placebo-controlled trial is ultimately what led to the voluntary withdrawal of the drug.
That trial was designed to evaluate whether Vioxx could prevent recurrence of colorectal polyps.
Topol said he hopes to see the government scrutinize all the facts of the Vioxx case, including direct communication between Merck and the FDA.
“We need to fix the FDA so we don’t have something like this again,” he said.
Kathleen Quinn, a spokeswoman for the FDA, said the agency has been aware of cardiovascular issues relating to Vioxx, has looked into them and has taken appropriate action. She noted the FDA implemented labeling changes in April 2002 to include information about such events as heart attacks and strokes.
In a separate piece for the journal, Dr. Garret FitzGerald of the University of Pennsylvania raised concerns about all COX-2 inhibitors, or coxibs, a subset of nonsteroidal anti-inflammatory drugs that includes Pfizer’s Celebrex and Bextra.
Pfizer has asserted its drugs are safe. But given the Vioxx findings, FitzGerald wrote, “It is essential to determine whether the cardiovascular risk is or is not a class effect. The burden of proof now rests with those who claim that this is a problem for [Vioxx] alone and does not extend to other coxibs.”