Merck's Vioxx Pain Lingers

At last, the Vigor study -- completed in 2000 -- examined the cardiac risks associated with Vioxx. It showed a fivefold increase in heart attacks. Singh, who was conducting his own research in this area, felt "stunned."

He sought additional information from Merck but, for the first time, found the company uncooperative. Indeed, he said, the company actually threatened him.

"I persisted in my inquiries and I was warned that if I continued in this fashion, there would be serious consequences for me," Singh said. "Subsequently, I learned that this was a persistent pattern of intimidation."

Only after Stanford complained to Merck's CEO, Singh said, did threats from the company stop.

By the end of 2000, results of the Vigor study had surfaced in the New England Journal of Medicine. Public Citizen, a consumer watchdog organization, placed Vioxx on its "worst pills" list a few months later.

Eric Topol, head of cardiology at the Cleveland Clinic, followed up with yet another damaging Vioxx study shortly afterward. But Merck consistently fought back.

"Each time a study was presented or published, there was a predictable and repetitive response from Merck, which claimed that the study was flawed and that only randomized, controlled trials were suitable for determining whether there was any risk," Topol wrote last fall in the New England Journal of Medicine. "But if Merck would not initiate an appropriate trial -- and the FDA did not ask them to do so -- how would the truth ever be known?"

Topol specifically blames senior executives at Merck and leaders at the FDA for the Vioxx fiasco. Merck secured a "priority" review, spanning only six months, for approval of Vioxx. The heavily advertised drug hit the market in the summer of 1999. The first study to examine its heart risks had not even ended.

Bruce Psaty, an epidemiologist and drug safety expert, suggests that timing made a big difference.

"If the Vigor trial results had been available ... it's possible the FDA never would have put Vioxx on the market," he said.