Clear Thinking About Vioxx

The risk is not what you think.

David Henderson & Charles Hooper | January 3, 2005

(Page 2 of 3)

CBS' 60 Minutes starts its November 14 segment on Vioxx with the story of a healthy, beautiful 39-year old, Janet Huggins, who died within a month of starting to take Vioxx. CBS goes on to say:

Instead, Merck found something potentially worse: Patients taking Vioxx for longer than 18 months were twice as likely to suffer a heart attack or stroke than those taking a placebo.

CBS then shows Huggins' husband saying that he's sure that Vioxx killed his wife. But 18 months is not one month. Merck has solid evidence that Vioxx shows no additional cardiovascular risk until after 18 months of therapy. The odds that Mrs. Huggins died from Vioxx are slim indeed. But that didn't stop CBS from exploiting her death to make a point.

Merck's Responsibility

Of course, our view of Merck might change if we had reason to think that Merck withheld evidence of Vioxx's harmful side effects. But so far we have no basis for thinking Merck did withhold evidence and, in fact, we have a strong basis for believing that it didn't.

First, let's consider the easy case. No one seems to think that Merck moved too slowly in withdrawing Vioxx within four days of getting the results from the aforementioned APPROVe study. So the issue comes down to whether Merck withheld information from earlier studies.

The closest anyone has come to a "smoking gun" is an email about the VIGOR study that Merck's chief of research, Edward Scolnick, sent to his colleagues. Here's how The Wall Street Journal put it:

On March 9, 2000, the company's powerful research chief, Edward Scolnick, e-mailed colleagues that the cardiovascular events "are clearly there" and called it a "shame." He compared Vioxx to other drugs with known side effects and wrote, "there is always a hazard." (Anna Wilde Mathews and Barbara Martinez, "E-Mails Suggest Merck Knew Vioxx's Dangers at Early Stage," Wall Street Journal, November 1, 2004.)

In that same e-mail, Scolnick lamented, "it is a shame but it is a low incidence and it is mechanism based as we worried it was." In other words, Scolnick was saying that, contrary to what Merck researchers had believed, the higher incidence of heart attacks was due not to the fact that people taking Vioxx weren't taking NSAIDs but rather to something within Vioxx itself. This does sound like a cover-up. But notice something interesting in the time line that some anti-Vioxx lawyers put together. The next event they note after the March 9 email is that on March 17, only eight days after Scolnick's speculation, Merck updated its label by adding, in the "adverse events" section, "cardiovascular" reports. Some cover-up.

60 Minutes breathlessly added:

However, according to internal Merck documents 60 Minutes has seen, and interviews with outside scientists, Merck had concerns that Vioxx could possibly cause cardiovascular risks long before it was pulled off the market.

Of course they had these concerns. Those risks were known from the VIGOR trial, which was completed in March 2000, and whose results were reported to the FDA in June 2000.

Beginning in September, 2002, this new information was printed on the Vioxx package insert. It was reprinted, shortly after that, in the widely used 2003 version of the Physicians' Desk Reference. The package insert devotes two full tables and a number of paragraphs to the risk of cardiovascular problems. The package insert shows that 45 of 4,047 patients on Vioxx experienced a cardiovascular thrombotic event, compared to only 19 of 4,029 patients on naproxen. The package insert goes on to say that Vioxx is not a substitute for aspirin and that patients who need cardiovascular protection should continue taking aspirin. It also notes the additional one in 4,000 risk of a fatal heart attack.

The real test of whether Merck was responsible is a market test: after this information was revealed to the public in September 2002, did the demand for Vioxx decline? If it didn't decline substantially, that suggests that people taking Vioxx were not very concerned about this small additional risk. You might argue that people are not informed enough to know about this risk. But their doctors are, and doctors, in the U.S. at least, write all the prescriptions for Vioxx. Doctors regularly page through the Physicians' Desk reference and word on Vioxx would have been out by early 2003. Yet the worldwide demand for Vioxx grew slightly while the U.S. demand declined slightly. The U.S. decline of five percent between the second quarter of 2003 and the second quarter of 2004, was so small that it could have been due to a number of other factors, including competition from similar drugs such as Celebrex. (Celebrex has also been linked to an increased risk of cardiovascular problems, but the drug's manufacturer, Pfizer Inc. has chosen not to withdraw it from the market.)

There's another test of Merck's responsibility or lack of same: look at the behavior of Merck employees, especially those intimately involved with the VIGOR study. After learning of the VIGOR results, did those employees who took Vioxx stop taking it? We don't know, but those data are relevant and, in fact, Merck would do well to gather them for its legal defense. And we do know one sample point. Merck's CEO, Ray Gilmartin, told a congressional committee that his wife took Vioxx until the day the company withdrew the drug. Unless we speculate that he was out to kill his wife slowly, and was willing to accept a low probability of succeeding, his and her behavior are powerful evidence that Merck was selling a drug it considered relatively safe.