Merck overruled researcher's concern about Vioxx in 2000

Records indicate alarm after death in clinical trial


In 2000, amid rising concerns that its painkiller Vioxx posed heart risks, Merck overruled one of its scientists after he suggested that a patient in a clinical trial had probably died of a heart attack.

In an e-mail exchange about Vioxx, the company's most important new drug at the time, a senior Merck scientist repeatedly encouraged the researcher to change his views about the death "so that we don't raise concerns." In subsequent reports to the Food and Drug Administration and in a paper published in 2003, Merck designated the cause of death as "unknown" for the patient, a 73-year-old woman.

The discussion of the woman's death is contained in several previously undisclosed Merck records, including e-mail messages from Dr. Edward M. Scolnick, Merck's top scientist from 1985 until 2002, and from Dr. Alise S. Reicin, a vice president for clinical research, that indicates Merck's concerns about data contradicting its view that Vioxx was safe.

In one e-mail message, Scolnick said the drug trial that included the woman's death had "put us in a terrible situation." In others, Scolnick fiercely criticized the Food and Drug Administration and said that he would personally pressure senior officials at the agency if it took action unfavorable to Vioxx. As lawsuits against Merck over Vioxx move toward trial, the documents could help plaintiffs paint a picture of the company that is at odds with Merck's public statements that it had no evidence of Vioxx's cardiac risks until last fall.

Theodore V.H. Mayer, a lawyer for Merck, said that the company had disclosed all information from clinical trials to the FDA, and that Scolnick's e-mail messages merely reflected his concern that the FDA weigh Vioxx's benefits and risks fairly. The e-mail discussion between the Merck scientists reflected an honest scientific debate over the cause of the woman's death, Mayer said.

Merck withdrew Vioxx in September after a different clinical trial found the drug increased the risk of heart problems. More than 25 million Americans took Vioxx between 1999 and 2004, and at least 4,600 people or their survivors are suing the company, claiming Vioxx caused their heart attacks or strokes. The first individual cases are scheduled for trial next month in Alabama and Texas, filed by the survivors of two men who the suits say died of heart attacks after taking the drug.

Merck, the nation's third-largest drug maker, has said it plans to contest every suit. The company says it did everything reasonably possible over the years to determine whether Vioxx caused heart problems and to disclose the drug's risks to patients and doctors. The e-mail messages and other internal Merck documents, including the report of the woman's death, were provided to The New York Times by a person working with plaintiffs.

The death of the 73-year-old woman - who was not identified by name in the documents and whose identity has not been disclosed - occurred during a 12-week clinical trial called Advantage that covered 5,500 patients. Clinical trials are at the core of the development of new medicines, providing data that enable the FDA and doctors to weigh drug risks and benefits.

Mayer said the doctors involved in the e-mail exchanges could not be certain whether the woman who died was taking Vioxx or an older painkiller, naproxen, that was used in the trial, because information about which participant was taking which drugs was kept confidential. But at the time, there was widespread concern within the company about the relationship between Vioxx and heart attacks as a result of troubling earlier research.

During the Advantage trial, eight people taking Vioxx suffered heart attacks or sudden cardiac death, compared with one taking naproxen, according to data released by the FDA this year. The difference was statistically significant, but Merck never disclosed the data that way.

Back in 2000, Merck was struggling to explain the results of another study, called Vigor, which also indicated that patients taking Vioxx had more heart attacks than those taking naproxen, which is found in such over-the-counter drugs as Aleve. Unlike the Advantage results, the Vigor results had been publicly disclosed by Merck.

Scolnick expressed his worry in e-mail messages to other senior Merck scientists that the Advantage results would encourage the FDA to demand that Vioxx's label highlight its cardiac risks. Such a change would have damaged Vioxx's sales, especially because a competing drug, Celebrex, did not have heart risks prominently displayed on its warning label.

In e-mail messages April 7, 2001, to Dr. Douglas A. Greene, an executive vice president at Merck Research Laboratories, Scolnick wrote that he was especially angry because the Advantage trial had no scientific purpose. In theory, Merck set up the trial to show that Vioxx caused fewer stomach problems than naproxen. But Merck had demonstrated that with the Vigor trial, which tracked more than 8,000 patients for a year.

Baltimore Sun Articles
Please note the green-lined linked article text has been applied commercially without any involvement from our newsroom editors, reporters or any other editorial staff.