Journal Raises New Questions About 2000 Vioxx Study

The prestigious New England Journal of Medicine is publishing more criticism of a 2000 study on Vioxx. The journal says at least two researchers knew about "adverse cardiovascular events" more than four months before the article was published. Merck removed Vioxx from the market in 2004 and faces thousands of Vioxx-related lawsuits.

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There is renewed controversy over a scientific study published five years ago on the safety of the painkiller Vioxx. The journal that published the study is the authoritative New England Journal of Medicine. Two months ago, the journal's editors said scientists conducting the study withheld information about heart problems among patients on Vioxx. Now the journal is publishing a response from those scientists and repeating its own concerns about the study.

NPR's Snigdha Prakash reports.


Vioxx, of course, is the blockbuster painkiller that was used by an estimated 20 million Americans. In 2004 its manufacturer, Merck, released data showing that Vioxx increased heart attacks and other coronary problems. The company took Vioxx off the market. It now faces close to 10,000 product liability lawsuits by patients and their families who say they were harmed by Vioxx.

The scientific study in question was published in the New England Journal in the fall of 2000, some 18 months after Vioxx came on the market. It was widely cited by Merck because it showed that Vioxx caused fewer gastrointestinal problems than an older painkiller, Naproxen. But the study also turned up something else; patients on Vioxx had four times as many heart attacks as those on Naproxen. The study scientists interpreted those findings to mean not that Vioxx was dangerous, but that like aspirin, Naproxen protected patients from heart problems.

Last December, as the third product liability suit against Merck went to a jury in Houston, the New England Journal published an editorial. It said that court documents had revealed that Merck scientists knew about more heart attacks than they included in their study back in 2000. The journal's editors said that including the additional heart attacks would have made Vioxx look much riskier.

In their responses to that editorial, published online Wednesday, the scientists, from academia and from Merck, defended their original study and its conclusions as scientifically appropriate. Here's what they said. They said the three additional heart attacks that were missing from the New England Journal paper weren't in there because they were not reported until after an established cutoff date. That date was February 10, 2000. Information on the three missing heart attacks came in between February 16th and February 22, 2000.

The Merck scientists defended the omission. They wrote, quote, "Adherence to a pre-specified plan is routine and appropriate when reporting scientific data, precisely because this practice avoids later allegations that they were manipulated," end quote.

But what is a pre-specified plan? Documents obtained by NPR showed that it wasn't until February 7th that Merck scientist Alise Reicin committed to the February 10 cutoff date. She said that cardiovascular events reported to Merck by that date would be analyzed. Merck says that the crucial point is not when the date was established, but that the cutoff was set before scientists knew what the study outcome was.

The Merck scientists also said they disclosed all the cardiovascular events to the Food and Drug Administration promptly. In fact, an internal Merck email obtained by NPR shows that the company knew about heart problems reported after the cutoff date, but did not include them in a study report filed in late June 2000 with the Food and Drug Administration. The events weren't disclosed to the FDA until October.

The Vioxx scientists also said the additional heart problems would not have materially effected the outcome of the study. The New England Journal editors disagreed. They pointed out that had all the data on cardiovascular adverse events been included, the missing heart attacks, strokes, various serious clotting events, it would have shown that the gastrointestinal benefits of Vioxx came at the expense of serious cardiovascular events.

Snigdha Prakash, NPR News, Washington.

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