Merck Canceled an Early Study of Vioxx

By BARRY MEIER

Published: February 8, 2005

Merck & Company executives have long insisted that they never pursued a clinical trial to directly study the heart risks of the pain drug Vioxx because other tests they were conducting would supply those answers just as quickly.

But previously undisclosed company documents show that the drug maker was poised to begin a major cardiovascular study of the drug in 2002, and abruptly dropped the project just before it was set to start. The trial was scheduled to produce data by March 2004 but may have provided answers about Vioxx's risks even earlier if patients had shown ill effects.

It was not until September 2004 that Merck halted a separate study when patients in that trial experienced heart attacks and strokes at twice the rate of those receiving a placebo. At the same time, Merck withdrew Vioxx from the market.

In a statement, Merck said it had decided not to do the study because, among other things, it would have involved "high-risk" patients. The test in question would have involved patients with acute coronary syndrome, a condition characterized by chest pain from cardiovascular disease.

Merck officials briefly cited their plan to run a study in patients with chest pain as part of a 176-page document recently submitted by the company to the Food and Drug Administration. It submitted the document ahead of agency hearings next week on problems with a class of widely used pain relievers known as COX-2 inhibitors, which include Vioxx, Celebrex from Pfizer and other drugs.

However, Merck has never disclosed how extensively it planned that study, which was known inside the company as the Valor trial, or how close it came to starting it. By early 2002, the drug maker had already contacted outside researchers to oversee the test, had approached a competing drug maker to obtain anti-ulcer drugs to ease the possibility of side effects, and had prepared a 70-page protocol that spelled out how the test was to be conducted, according to documents reviewed by The New York Times.

One planning document, for example, shows that the first patients were supposed to enter the study in June 2002 and the last patient was to leave it in January 2004. But in mid-March 2002, just days before company researchers had planned to submit the study's protocol to the F.D.A., top executives of the drug maker ordered work on the project halted. It was never revived.

"I have the unpleasant task of having to inform you that the VIOXX CV Outcomes Study has been placed on hold," a memo dated March 13, 2002, and sent to dozens of Merck employees worldwide, stated. "At this time we do not have any of the details that led to this decision, however, we have been informed that upper management is in the process of reviewing the various study options."

In a statement issued yesterday, Merck said that even after the company had developed the trial's protocol "we continued to ask ourselves and our consultants whether this was the right study to definitively answer" the question of whether Vioxx posed cardiovascular risks. "We ultimately decided not to conduct that particular study." In clinical trials, drug companies usually retain outside specialists as consultants who help design the trial.

Merck officials have previously said that, rather than running a specific cardiovascular study of Vioxx, they decided to collect such data from studies in which Vioxx was being tested for other possible uses. One of those studies, which began in 2000, examined the drug's potential for preventing colon polyps. Two other studies, one of which started in 2002 and the other in 2003, looked at the drug as a possible treatment for colorectal and prostate cancer.

It was the result from the colon polyp trial that led Merck to withdraw Vioxx.

Work on the Valor trial was halted at the same time that officials from Merck and the F.D.A. were concluding lengthy and heated negotiations over how Vioxx's label would reflect data from an earlier trial, known as the Vigor study, which indicated that the widely used painkiller posed potential cardiovascular risks.

Merck officials said yesterday that the company's decision to not go forward with the planned trial was not related to those talks, which culminated in April 2002.

In its statement, Merck said both it and some of its consultants were also concerned that, because patients with acute coronary syndrome in the Vioxx study would also be taking low doses of aspirin to prevent heart attack and stroke, their experiences might not translate to patients who were not taking aspirin.

Joan Wainwright, a Merck spokeswoman, said it was not unusual for trial planning to go forward while company officials and consultants debated a study's merits. "There was a wide range of opinions about whether this was or was not the study we were going to do and in the end we decided it was not," she said.

Asked to provide a copy of a document from March 2002 which summarized the decisions given at the time for not going forward with the study, Ms. Wainwright said that no such document existed.