Healthy Skepticism Library item: 929

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Publication type: news

FDA should have required Vioxx safety study years ago, says Vanderbilt professor
SCRIP - World Pharmaceutical News 2004 Oct 4

Full text:

It only took a prospective, randomised, clinical study of 2,600 patients to confirm the first suggestion of a possible increased risk of heart attacks and strokes in patients taking Merck & Co’s Vioxx (rofecoxib), and such a study “should have been mandated by the FDA at an earlier stage”, says Dr Alistair Wood, a pharmacologist and professor of medicine at the Vanderbilt School of Medicine in Nashville, Tennessee.

In an interview with National Public Radio, Dr Wood (who two years ago was on a shortlist of candidates to become the next FDA Commissioner and in 1997 wrote an editorial in the NEJM calling for an independent drug safety board) said that the story of Vioxx was an indictment of the whole industry, because a much-needed confirmatory trial never took place after the first suggestion of a cardiovascular risk surfaced from the VIGOR study in 2000.
“More than 84 million people took this drug… We did nothing for four and half years and that is a big problem.”

After the first indication of a potential risk, the FDA took the findings of the VIGOR study along with other evidence to its advisory panel in February 2001, then changed Vioxx’s US data sheet in April 2002 to reflect the association with higher heart attack risk. In Dr Wood’s view, this was inadequate. “How did that help, since 2.5 million Americans were still taking the drug as of June?” he asked. “That doesn’t speak to the effectiveness of the warning.”

Dr Wood claimed that the Vioxx story was “a public health disaster” and that it needed to be taken as seriously as other disasters. “We need to have a public investigation of this, and we need a recommendation as to what needs to be done in the future to avoid the next Vioxx being taken by 84 million before we discover that a study of two and half thousand people would have shown the risk.”

Dr Wolfe concurs
It is certainly within the power of the FDA to mandate safety trials, Public Citizen’s Dr Sidney Wolfe told Scrip. Such studies should have been required not just for Vioxx but for the other COX-2 inhibitors as well. “The agency can do whatever it wants. It could have said that, with one of the drugs in the class, there has already been evidence of increased cardiovascular disease and that therefore the manufacturers need to conduct further studies or the agency will try to take the drugs off the market. There was enough reason to be concerned about risk.”

In the view of Dr Wolfe, the VIGOR study was clear, and should have been more of a warning sign.

Dr Wolfe says that at least the agency tried to get Merck to abide by some of the concerns arising from the VIGOR study. The study found that Vioxx was associated with an increased risk of heart attack, which led to Merck receiving a warning letter from the FDA in September 2001 because its ads for the drug failed to mention the increased risk.

In an eight-page warning letter, addressed to CEO Raymond Gilmartin, the FDA
stated: “You have engaged in a promotional campaign for Vioxx that minimises the potentially serious cardiovascular findings that were observed in the VIGOR study, and thus misrepresents the safety profile for Vioxx.
Specifically, your promotional campaign discounts the fact that in the VIGOR study, patients on Vioxx were observed to have a four to five-fold increase in myocardial infarctions compared to patients on the comparator NSAI, Naprosyn (naproxen).”

Overall, Dr Wolfe is critical of the way the FDA handled any concerns about Vioxx and heart attack risk. In April 2002, the US data sheet was changed to say that Vioxx might protect against ulcers but increase heart risks. “The warning was buried, and the FDA did not require a boxed warning and did not say that the product should be considered a last resort drug,” he said. The FDA is too passive, he added, and is becoming increasingly so with user fees coming from industry.