Matthew Herper and Robert Langreth, 10.14.04, 11:30 AM ET
NEW YORK - Should Merck have conducted a bigger trial to test the safety of its arthritis drug Vioxx?
Merck (nyse: MRK - news - people ) pulled Vioxx from the market two weeks ago, but questions about the heart safety of the drug date back years, to an August 2001 paper in The Journal of the American Medical Association.
That paper, by two top cardiologists, called for a big clinical trial to specifically prove Vioxx was safe for the heart. In December of 2001, Merck seemed to indicate it would mount such a study--but the clinical trial never seems to have materialized, even though the firm started a similar trial for Arcoxia, a successor drug to Vioxx.
According to Merck's press release from its 2001 annual meeting with Wall Street analysts, the company "announced plans to conduct a large cardiovascular clinical outcomes study with Vioxx and a separate cardiovascular outcomes trial with Arcoxia. The company expects to begin the multinational trials in 2002."
In September of 2002, Merck began a 23,542-patient study called MEDAL that was specifically designed to examine the heart safety of Arcoxia, a potential Vioxx successor. But the company began no comparable study for Vioxx.
Merck spokesman Tony Plohoros says that Merck's statement at the analyst meeting referred to its plan to gather and combine heart-safety data from three other studies, whose primary aim was to show Vioxx could prevent or treat cancer. One of these studies, APPROVE, begun in 1999, is what ultimately led to the recall. The second study, begun in 2002 with 7,000 patients, aimed to show whether Vioxx could prevent colon cancer relapse. The third study, which didn't start until 2003, was designed primarily to test whether Vioxx could prevent prostate cancer.
"There is no missing study," says Plohoros.
But some cardiologists disagree. Suggesting the cancer trials were cardiovascular tests is misleading and inappropriate, says Richard Milani, vice chairman of the department of cardiology at the Ochsner Clinic in New Orleans. "That would not suffice on the surface as a true cardiovascular outcomes study," says Milani.
Steven Nissen and Eric Topol are the Cleveland Clinic cardiologists who raised questions about the heart risk of both Vioxx and Pfizer's (nyse: PFE - news - people ) rival drug Celebrex in August 2001. Both reject the notion that cancer prevention trials could have settled the issue of Vioxx's safety.
"I don't think that makes any sense at all," says Nissen. "When you want to study a particular outcome, you have to design a study that includes patients who are at high risk or substantial risk for that outcome. There's no substitute for a definitive trial in the right population."
Says Topol, "These trials, the primary reason they were done was to get extended registration for Vioxx use. They were totally insufficient and inadequate [for assessing cardiovascular risk]."
One cardiologist thought Merck's approach was appropriate. "Those studies would provide good long-term cardiovascular data," says Christopher Cannon, a cardiologist at Boston's Brigham & Women's Hospital, who is working on the Arcoxia trial. "You can't do every possible study under the sun."
Nancy Hersh, a plaintiffs' lawyer at Hersh & Hersh in San Francisco, says that in other drug liability cases she has filed, companies have been hurt by not doing trials that they should have. The juries focused on "the fact that the studies could have been done to demonstrate safety or efficacy but they weren't," she says.
Hersh, who filed an early case against Wyeth (nyse: WYE - news - people ) for its recalled diet drugs and has also been litigating against Eli Lilly (nyse: LLY - news - people ) for its antipsychotic Zyprexa, has already taken on some Vioxx cases against Merck. "It's too bad," she says, "because there's an inherent conflict of interest in all of this between the safety of the public and the bottom line of the manufacturer."
Quelle