Prescription For Trouble

Ed Bradley Reports On The Painkiller Vioxx

(CBS)  Merck says that study was too small and not statistically significant enough to be able to draw any conclusions. But Topol maintains that, combined with the VIGOR trial, it showed that by the year 2000, there was solid evidence that Vioxx was not safe. Merck says Topol's methodology was flawed and disputed his findings.

"Merck took on any study that questioned the safety of Vioxx, with respect to the heart attacks and strokes. Any study," says Topol.

"But can't they say on the other hand, 'OK, there are always dissenters. We've got these other studies that say the drug is fine,'?" asks Bradley.

"Whenever you find a problem and you're thinking maybe it's not a problem, you want to see if there's independent replication," says Topol. "So if you have Study '090', and you want to discount that somehow, then you have VIGOR. You've got two trials now. You have essentially lightning striking twice. That's independent replication. That's really serious confirmation. This is unequivocal. This is a problem."

Merck says while it was concerned about the cardiovascular risks seen in the VIGOR study, it was not conclusive evidence that Vioxx caused heart attacks. And the company points out that it conducted a number of studies before and after FDA approval, which did not show the heart risk seen in the VIGOR study.

As safety questions about Vioxx continued to be raised in medical journals, Merck continued its $500 million advertising campaign. The company had developed a training document 60 Minutes obtained called "Dodge Ball Vioxx," which instructs Merck sales representatives how to promote the drug to physicians.

The document consists of a 12-page list of obstacles. These are questions a doctor could pose, such as "I am concerned about the cardiovascular effects of Vioxx."

A former Merck sales representative told 60 Minutes how she was trained to answer that question. She asked that 60 Minutes not use her name, and that 60 Minutes alter her appearance and voice.

"We were supposed to tell the physician that Vioxx did not cause cardiovascular events; that instead, in the studies, Naproxen has aspirin-like characteristics which made Naproxen a heart-protecting type of drug where Vioxx did not have that heart-protecting side," she said.

The FDA says there is no conclusive evidence that Naproxen protects the heart. Merck told 60 Minutes the use of the word "dodge" was unfortunate and that the company instructed its sales force to be honest and straightforward about Vioxx.

The former sales representative we spoke to told us she feels the company betrayed her: "I put my reputation on the line. I gave my physicians my word that Vioxx was a safe, effective product and it's been pulled from the market because it was killing people."

Merck's marketing campaign didn't sit well with the FDA, which sent a warning letter to the company in September 2001, saying that sales representatives "have engaged in false or misleading promotional activities," and that the company's promotional campaign "minimizes the potentially serious cardiovascular findings" about Vioxx.

Janet Woodcock, acting deputy commissioner of the FDA, says her agency took appropriate action based on the Vioxx studies. "Certainly, we were concerned," says Woodcock.

"If you were concerned, you weren't concerned enough to pull it off the market," says Bradley.

"That's correct," says Woodcock. "Here we had a new benefit, and I think it's important to recognize that there are many thousands of deaths every year from the gastrointestinal toxicity of the anti-inflammatory agents.

"On the other hand, we had, as you said, a red flag for clotting, for cardiovascular events. But we didn't know what it meant. There were other studies that did not show this increase with the ordinary dose of Vioxx, and more study was needed to understand what this meant."

Looking back, was there anything the FDA should have done?

"I think we were on top of the case here," says Woodcock. "And we did what we could to get all the evidence together and keep information flowing."

The FDA says Merck made certain changes, including changing the Vioxx package label in 2002 disclosing cardiovascular risks. But that was more than a year after the FDA asked the company to do so.

The British medical journal The Lancet published a study that concluded, based on an analysis of previous studies, Vioxx should have been "withdrawn several years earlier."

While Merck disputes that finding, Topol says there is a lesson to be learned.

"In trying for now two decades in my career to try to prevent heart attacks and treat heart attacks, to have a medicine that's causing heart attacks and strokes is something that can't be tolerated," Topol says. "These are the two biggest, most important killers in our society. And then it's important that we never have something like this happen again."

Vioxx isn’t the only pain medication to raise safety concerns. In April, the FDA persuaded Pfizer to withdraw its popular drug Bextra from the market and issued a requirement that more than a dozen similar pain drugs (such as Celebrex) carry strong warnings about cardiovascular risks.