Official at FDA Warns of Drug Risks

WASHINGTON -- In devastating testimony before a Senate panel yesterday, a whistle-blower at the Food and Drug Administration shocked a packed hearing room when he listed five drugs now on the market that he thinks are dangerous and accused the agency of stifling its own scientists who raise safety questions.

Dr. David Graham, an FDA drug-safety official, said the agency and drug giant Merck, didn't move fast enough to take the painkiller Vioxx off the market.

He said that because of the FDA's flawed structure, Americans are left "virtually defenseless" against dangerous pharmaceuticals.

"I would argue that the FDA ... is incapable of protecting America against another Vioxx," he said, because of the FDA's close relationship to the drug companies it regulates.

He was testifying before the Senate Finance Committee, which is looking into the FDA's drug-approval process.

Merck pulled Vioxx off the market in September in light of new information about its risk of heart attacks.

Graham said an earlier estimate that Vioxx may have caused 27,000 heart attacks was "extremely conservative." He said the drug may have caused as many as 139,000 heart attacks, leading to as many as 55,000 deaths.

Graham stunned the hearing room when he listed, when asked by a senator, five other drugs now in use that he thinks present safety problems: Meridia, a weight-loss drug; Crestor, an anti-cholesterol drug; Accutane, an acne drug linked to birth defects; Bextra, a painkiller; and Serevent, an asthma treatment. Makers of the drugs defended the safety of their products.

Graham said Serevent was shown, in a long-term trial in England, to cause asthma-related deaths. "We've got case reports of people dying, clutching their Serevent inhaler," Graham said. "But Serevent is still on the market."

The FDA approved Vioxx in 1999, just months before Merck released a study that showed an elevated number of heart attacks among Vioxx users. Merck downplayed the study results and kept the drug on the market until September.

In 1999, while Merck was estimating how much Vioxx it could sell, doctors at Group Health Cooperative in Seattle reviewed those results and other data on Vioxx's safety. Group Health's physicians decided not to make the drug available for its half-million members, citing the risks that eventually would lead to its withdrawal, Dr. Bruce Psaty of the University of Washington told Congress yesterday.

Psaty, co-director of UW's cardiovascular-research center and a researcher who works with Group Health patients, said Merck and FDA should have acted earlier on studies and signals regarding Vioxx's potential to cause heart attack and stroke.

Psaty was a key witness in a packed hearing, in which Merck and the FDA came under fire from panel chairman, Sen. Charles Grassley, R-Iowa, who called Vioxx "the worst drug disaster in America's history."

Seating was so hard to come by that trial lawyers and industry lobbyists paid people to stand in line for seats for them.

Psaty said that if Merck had completed its 1999 study several months sooner, "Vioxx might not have been approved."

He called on the FDA to institute an independent office to review drug safety "to prevent another disaster like this one."

Merck's Chief Executive Officer Raymond Gilmartin and a FDA official defended their organizations' handling of Vioxx, which generated sales of $2.5 billion last year.

Gilmartin said the company did not have convincing clinical trial evidence of heart-attack risk until just days before the drug was withdrawn. Before that data, "there was no demonstrated increased risk of cardiovascular events for patients taking Vioxx," he said.

But Group Health's Director of Studies, Dr. Eric Larson, who helped Psaty prepare his testimony, reviewed issues surrounding Vioxx in 1999. "We at Group Health decided not to use Vioxx when it came out, because we did not see enough evidence of its safety, or efficacy," Larson said.

Group Health is a nonprofit cooperative that provides care for more than 500,000 people in Washington and Idaho.

Larson said Group Health has rejected several highly touted and heavily advertised drugs for use by its subscribers that later were withdrawn from the market for safety reasons.

They include Baycol, a cholesterol drug; Seldane, an antihistamine; the diet-drug duo fen-phen; Rezulin, a diabetes medicine; and Posicor, a cardiac drug.

After the hearing, Graham was asked how he became a FDA whistle-blower. He said, "I didn't start out that way. The FDA made me into one."