Drug safety crusader gets results, criticism

Back in the '60s, when University of Michigan students were holding protests over civil rights and the Vietnam War, an undergraduate named Steven E. Nissen was at the center of the political dissent.

Four decades later, that former campus activist is now Dr. Nissen, who is shaking up the nation's pharmaceutical industry.

His questioning of the safety of the Avandia diabetes medication in late May, for example, prompted a federal safety warning and led to a sales decline of about 30 percent for the drug, which brought in $3.2 billion for GlaxoSmithKline last year. Now, with a federal panel soon to decide whether it can remain on the market, Avandia's future is uncertain.

The drug is the latest example of why Nissen, 58, whose day job is chairman of cardiovascular medicine at the Cleveland Clinic, has emerged as a Naderesque figure and America's unofficial arbiter of drug safety.

Admirers laud him not only for raising safety questions about Avandia, but also for sounding early warnings about the painkiller Vioxx, as well as other drugs. By digging deeply into companies' clinical trial data -- information that used to be available only to federal drug regulators who did not always mine it as aggressively -- Nissen is among a new cadre of activist scientists demanding greater vigilance on drug safety.

But Nissen also has critics, who say he seeks the spotlight as much as the safety of medicine. Others see a conflict of interest in his self-appointed role as the drug industry watchdog while he also presides over industry-financed research worth millions of dollars. "I'm an insider and an outsider at the same time," Nissen says in an official Cleveland Clinic biography.

His crusading for drug safety, and his recent informal advisory role to members of Congress on legislation to strengthen drug safety enforcement, have fostered speculation that Nissen, a Democrat who has worked with members from both parties, covets an official public platform. Some see him angling to be the commissioner of the Food and Drug Administration, an agency whose decision-making he has frequently questioned.

Although Nissen denies that he is campaigning for the job, or that he is interested in it, he refuses to rule it out. "I want to fix the FDA," he said in a recent interview.

He also wants to influence health policy more generally. In one of his final acts this year as the president of the American College of Cardiology, a doctors' group, Nissen gave a speech calling for universal health insurance.

People listen to Nissen partly because of his unabashed self-confidence and outgoing personality. Friends from college remember his mischievous air, a demeanor that has endured alongside his willingness to raise tough questions.

Nissen also has a statistician's zeal for drilling deep into clinical data, seeking signs that some widely used drugs pose undisclosed risks to patients. In discussing his work, he describes sleepless nights poring over numbers.

His article in The New England Journal of Medicine, published in May, was based on his review of 42 clinical studies of Avandia involving nearly 28,000 patients. His conclusion, that the drug seems to raise the risk of heart attacks, was widely covered in the news media .

After the Nissen article appeared on the journal's website on May 21, the FDA, which said it had been evaluating the drug's risks, issued a safety alert advising patients who use Avandia to consult their doctors.

The agency also scheduled a hearing on July 30, at which a panel of expert advisers could recommend restrictions, or even a ban, on Avandia's use. The FDA has asked Nissen to attend to answer questions. GlaxoSmithKline has challenged the significance of Nissen's findings and has defended the drug's safety.

Avandia, which has been used by about 7 million people, is the latest drug to become a target of Nissen, who describes himself as an advocate of patients.

In 2005, for example, Nissen attacked the experimental diabetes drug Pargluva, from Bristol-Myers Squibb, saying it posed serious heart risks. Although an FDA advisory panel had overwhelmingly recommended its approval, Pargluva never made it to market.

Nissen, who had warned of the dangers of the painkiller Vioxx, from Merck, before it was withdrawn in 2004, challenged Merck's follow-on product, Arcoxia, which failed to win approval this year. He called Arcoxia the "son of Vioxx," telling a reporter, "This is a genie I don't want to see let out of the bottle."

In his article on Avandia, Nissen was careful to note the limitations of his analysis. In some media interviews, though, he was less guarded. On the ABC television program "Nightline," Nissen predicted that the deaths caused by Avandia could "dwarf" the carnage of Sept. 11, 2001.