It is perhaps the biggest drug scandal of recent years. Before Merck withdrew Vioxx in 2004, the popular painkiller was linked to heart attacks in tens of thousands of people. Now researchers have alleged that Merck knew of the dangers years earlier, but tweaked statistics and hid data so that regulators remained in the dark.

Vioxx was a blockbuster drug for Merck in the 5 years it was on the market, generating billions of dollars in revenue. After it was linked to heart attacks and strokes, the firm pulled its product, and earlier this year Merck agreed to provide almost US$5 billion in compensation to those claiming to have been harmed.

But an analysis of documents released during the litigation process that led to that settlement, carried out by Richard Kronmal, a statistician at the University of Washington, Seattle, who acted as an expert witness in the Merck lawsuits, suggests that company scientists were aware of the problems well before 2004.

Internal report

Kronmal’s study, co-authored with colleague Bruce Psaty, focuses on a 2001 internal company report. In it, Merck staff describe two recently completed trials involving around 1000 patients on Vioxx and a roughly equal number taking a placebo. Thirty-four people taking the drug died, compared with just 12 on the placebo.


But when Merck submitted the results to the US Food and Drug Administration (FDA) the same year, the company analysed the data in a different way. Deaths that occurred after patients completed their course of Vioxx appear to have been removed from the results, even though the drug can cause problems after patients stop taking it. Removing the deaths reduced the risk attributed to Vioxx.

The studies still prompted the FDA to ask whether the risk associated with the drug was enough to warrant stopping another ongoing trial, but Merck replied that it wasn’t. According to documents cited by Psaty and Kronmal, the company described the increase in mortality – which its own report revealed to be threefold – as “small numeric differences most consistent with chance fluctuations”.

A Merck statement, released to coincide with the Psaty and Kronmal paper, does not address the allegations in detail, but says that the company has analysed the trials and “found that there was no pattern suggesting the deaths had any connection to Vioxx; some of the deaths were caused by car accidents, poisonings, infections and other causes that are not related to Vioxx”.

The full set of documents released during the trials also contains details of other possible tactics employed by Merck. When a study suggested that Vioxx was more dangerous than a rival drug, for example, the company is alleged to have decided not to publish the results or properly inform the FDA.

Expert witness

David Egilman, a public health researcher and advocate at Brown University in Attleboro, Massachusetts, acted as an expert for Vioxx plaintiffs and has also analysed the internal documents. He says the documents contain descriptions of an experiment, known as Protocol 906, that compared the response of around 450 arthritis patients to Vioxx and Pfizer’s drug, Celebrex. The two drugs performed equally well, but the rate of side effects among Vioxx users – around 10% – was roughly twice that of those on Celebrex.

Egilman says the documents also contain an email in which a Merck employee tells a co-worker that “this is a very serious result and you will hardly be surprised by the idea of keeping this VERY TIGHT for the moment”.

Egilman adds that the results of Protocol 906 were never published or made clear to the FDA. Merck did not respond to a request from New Scientist for comment on Egilman’s analysis.

Critics say problems with data manipulation are due to intense pressure on drug companies to chase the multi-billion revenues generated by blockbuster drugs.

“It completely clouds your ethical responsibility,” says Merrill Goozner, director of the Center for Science in the Public Interest in Washington, D.C.

Journal reference:Journal of the American Medical Association (vol 299, p 1813)