Vioxx:
How Marketing Drives the Pharmaceutical Industry

Firm misled doctors on Vioxx, panel says
Sales staff told not to discuss risk study 

BERNADETTE TANSEY / San Francisco Chronicle 6may2005

Merck & Co. trained its sales staff to mislead doctors in an aggressive campaign to boost prescriptions for its painkiller Vioxx despite evidence that the drug increased heart attack risks, according to a House committee analysis of company documents.

Vioxx, which was withdrawn from the market in September because of heart attack and stroke risks, built up sales topping $2 billion during a period when safety concerns were mounting among scientific experts and federal regulators, said Rep. Henry Waxman, D-Los Angeles, at a hearing of the House Government Reform Committee on Thursday.

Doctors were induced to write millions of Vioxx prescriptions by Merck sales strategies that amounted to "disinformation and censorship,'' said Waxman, whose staff analyzed 20,000 documents related to the promotion of Vioxx.

A Food and Drug Administration official said Merck's practices weren't illegal. But the revelations could bolster moves by Congress to beef up the FDA's powers and possibly prove a bonanza to plaintiffs in civil suits against the drug giant claiming that Vioxx caused severe side effects, or death.

Sales representatives who visited physicians at their offices and hospitals were told to make spurious claims of superior cardiovascular safety for Vioxx, but they were forbidden to discuss Merck's own 2000 study linking the drug to heart attack risks five times greater than those with another painkiller, the report concluded.

Those sales practices continued while Merck was resisting the FDA's efforts to include a warning on Vioxx's label about cardiovascular dangers, according to the analysis.

A Merck spokesman maintained that the company's marketing practices were "fair and balanced'' and noted that doctors had every opportunity to read the 2000 study that raised questions about Vioxx's cardiovascular safety because Merck published it.

"We promptly disclosed the results of this clinical trial and our interpretations of it to the FDA, physicians, the scientific community and the media,'' said Dennis M. Erb, vice president of global strategic regulatory development.

The House committee's dissection of Merck's sales practices came on the same day longtime company chief Raymond Gilmartin was being replaced by senior manager Richard Clark, a shakeup seen as an attempt to revive Merck's falling fortunes.

In addition to the loss of Vioxx revenues and other setbacks, the company is beset by personal injury lawsuits related to Vioxx that could cost Merck tens of billions of dollars.

Erb, however, told the House committee that Merck was discussing with the FDA the possibility of returning Vioxx to the market. Vioxx is part of a class of painkillers known as the COX-2 inhibitors, which include Celebrex and Bextra. They were once hailed as the solution to the dilemma of patients with arthritis and other ailments whose older remedies for chronic pain can sometimes cause stomach bleeding.

Some evidence indicates that Vioxx causes fewer gastrointestinal side effects than some older painkillers, though the makers of Celebrex and Bextra were never able to get that claim included on the drug labels. After Vioxx was withdrawn, the FDA concluded that all three drugs carried heart and stroke risks. It asked for Bextra's withdrawal but allowed Celebrex to remain on the market.

The controversy over cardiovascular risks for the COX-2 drugs -- which all achieved blockbuster sales -- has already focused scrutiny on the once- ubiquitous television ads that had promoted them directly to consumers. But the hearing opened a rare window into the tactics used to market drugs to doctors -- where the bulk of the money was spent to promote all three COX-2 inhibitors.

In the documents disclosed, Merck urged its 3,000 Vioxx salespeople to push the drug in campaigns tagged Project XXceleration and Project Offense, in which physicians' safety concerns were described as obstacles to sales that had to be overcome.

Sales representatives were offered $2,000 bonuses for making Vioxx sales goals and encouraged to compare their efforts to the struggles of historical figures like Martin Luther King Jr. -- a tactic that evoked outrage from Rep. Elijah Cummings, a black Democrat from Maryland.

"I'm tired of people dying because of prescriptions that should never have been prescribed,'' Cummings said.

The FDA officials who testified also took a bipartisan grilling about the agency's responsibility to control Merck's promotional practices and the delays that prevented a cardiovascular warning from being included on Vioxx's label until 2002.

"Just who is the FDA protecting, and what are the ethical responsibilities of pharmaceutical companies?'' said Minnesota Republican Gil Gutknecht. "Both the FDA and the pharmaceutical company sort of missed the mark.''

The committee focused on actions by the FDA and Merck during the period after March 2000, when a large company study called VIGOR first provided signals of cardiovascular risks -- only a year after Vioxx was approved for arthritis pain.

The study found five times as many heart attacks among those taking Vioxx as among those on another painkiller, naproxen. But Merck argued that the difference could be the result of a possible protective effect on the heart from naproxen -- not any damage caused by Vioxx. The FDA and Merck began negotiations over a cardiovascular warning on Vioxx's label.

The safety alarms were repeated at an FDA advisory committee meeting in February 2001, in a New York Times article that May and in a forceful paper in the Journal of the American Medical Association that August. The FDA advisors said doctors should be told about the VIGOR study.

But after each of those events, the committee analysis found, Merck told its sales staff not to initiate discussions of the VIGOR study with physicians. Instead, they were to offer information from a company-prepared "cardiovascular card'' that indicated Vioxx was eight to 11 times safer than other anti-inflammatory painkillers. If doctors inquired about the VIGOR study, the sales representatives were forbidden to discuss it. They were instructed to tell doctors to write the company for information.

Those limits were imposed because the VIGOR study was not yet included on Vioxx's label, Erb said, while the studies underlying the information on the cardiovascular card were part of the package of data submitted to the FDA prior to Vioxx's approval.

Waxman said no FDA rule prevented drug firms from discussing studies not mentioned on the label, especially if they suggest a safety risk.

"That would be an absurd result,'' he said. What's more, Waxman said, the safety claims made on the cardiovascular card were an ill-supported analysis of a melange of pooled studies that the FDA itself had refused to include on Vioxx's label.

In the meantime, the FDA was trying to reach an agreement with Merck over a cardiovascular risk warning. The agency lacks authority to simply impose the language it wants.

"We were trying to work out exactly what was acceptable to both sides,'' said Dr. Steven Galson, director of the FDA's Center for Drug Evaluation and Research. The label change wasn't made until April 2002.

Instead of the warning the FDA originally proposed, the committee found, the agency agreed to list a precaution and state that the significance of the VIGOR study was unknown. Merck's sales force then emphasized that statement of uncertainty.