The two Merck & Co. executives were somber as the company plane pitched and rolled through the remnants of Hurricane Jeanne on the night of Sept. 28. The turbulence outside the aircraft was an echo of the corporate tempest leading up to their trip.
For five days Merck had been struggling with what to do with frightening new data that showed that long-term use of their $2.5 billion arthritis drug Vioxx doubled the risk of heart attacks and strokes, confirming concerns raised by earlier studies. Now research lab director Peter S. Kim and general counsel Kenneth Frazier were flying to Boston to tell one of the men most responsible for Vioxx's success that Merck would be pulling the drug in two days.
As they sat at the former lab director's dining table that night, they watched Edward M. Scolnick, who had been a champion of the drug before he retired, take in the implications of the data and become "despondent," they said. Scolnick was the one who had thrown Merck's resources behind the creation of Vioxx, a painkiller with fewer gastrointestinal side effects than traditional drugs. Backed by a $195 million ad campaign, featuring testimonials from former skater Dorothy Hamill and music by the Rascals to appeal to aging baby boomers, Merck had sold Vioxx to more than 20 million Americans since its approval in 1999 and millions more worldwide.
Now their wonder drug was suddenly under a cloud and Merck officials faced a difficult decision about how to handle the catastrophe.
On Sept. 30, the company would take the dramatic step of withdrawing the drug, sending the price of its stock into a steep slide that wiped out a quarter of the company's value, a slide from which it has not yet recovered.
An examination of how and why Merck reacted offers an unusual look at how safety issues are handled in clinical trials once a drug is on the market and the complex business of weighing risks against benefits. Even as Merck was deciding to withdraw the drug, there were medical experts arguing that it should not. It also shows that federal regulators often rely on drug companies to tell them that a product is dangerous . The whole saga, industry experts said, raises unsettling questions about aggressive consumer marketing of drugs before their long-term safety has been proven.
Sen. Charles Grassley (R-Iowa) who has launched an investigation into the Food and Drug Administration's handling of Vioxx said one of the questions will be whether "a too cozy relationship between the FDA and drug companies is getting in the way of public safety."
Over the past two weeks The Washington Post had interviewed independent researchers who collected and reviewed the Vioxx data, company officials who decided how Merck would respond, critics of the drug industry and regulators who, in the end, played almost no role in its recall.
With Vioxx, researchers had been warning about the drug's possible cardiovascular risks since 2000, only a year after it was approved by the FDA. Data from a company study found then that users had four times as many heart attacks and strokes as those who used another painkiller. But the data was not definitive, and Merck, which even critics say is one of the most responsible drug companies, repeatedly reassured the medical and financial communities that Vioxx was safe.
Independent studies of Vioxx users continued to add to the questions, and the FDA began its own review. The safety officer who conducted it concluded this summer that the drug posed a serious risk. But he said that the results were ignored and that the FDA made efforts to silence him.