Is the FDA Doing Its Job?

First Vioxx, now Avandia. The news that this widely prescribed drug for type 2 diabetes might boost the risk of heart attack in some patients—though not yet scientifically confirmed—sent patients into a panic and once again raised questions on how well the Food and Drug Administration is doing as the country's watchdog on drug safety.

Some of those questions have been stinging. "We need to know if this is another Vioxx, where the FDA sat on its hands and endangered lives," thundered Sen. Chuck Grassley, R-Iowa, who began a congressional investigation.

The storm over Avandia, currently used by about 1 million Americans, broke on May 21 when the New England Journal of Medicine published a report by the Cleveland Clinic's Steven Nissen, M.D., former president of the American College of Cardiology. His analysis of 42 clinical trials suggested that the drug could cause a 43 percent increase in heart attack risk.

Avandia's manufacturer, GlaxoSmithKline, strongly disagrees with the findings, citing other, unpublished studies. Nissen himself acknowledges his analysis was "limited by a lack of access to original source data." Other experts say the issue is far from settled. "We don't know whether there's a small increased risk for everyone [on Avandia] or a very high risk for a few or no added risk at all," says Richard Hellman, M.D., president of the American Association of Clinical Endocrinologists. Even so, he adds, there was "absolutely a panic" among patients who called their doctors "within 24 hours of hearing it on the evening news."

FDA Commissioner Andrew von Eschenbach, M.D., defended the agency against accusations that it hadn't issued earlier alerts, telling reporters in May: "I believe we did it right in regard to Avandia." But in early June he announced that he had asked Glaxo and Takeda, which makes another diabetes drug, Actos, to place "black box" warnings—the strongest warning—about heart failure risks on their labels.

The incident has again raised the wider issue of how the FDA handles drug safety and to what extent Congress gives it the funds and regulatory teeth to do its job.

Fifteen years ago, faced with complaints from the drug industry that the FDA was taking too long to approve new drugs, Congress passed the Prescription Drug User Fee Act (PDUFA), allowing drug companies to help fund the process. That shortened the review time but also resulted, critics say, in the agency losing its scientific independence. Over time, the FDA has become "more focused on the industry and less on what the science is telling us and what is in the best interest of public health," says Susan Wood, a former FDA official and now a professor at George Washington University's School of Public Health.

Wood and 21 other leading scientists and physicians recently sent a letter to Congress asking it to rethink PDUFA. Drug approvals completed too quickly, they said, are often associated with later safety problems. In 1999 the eight priority new drugs the FDA approved in only six months or less included Vioxx—the painkiller withdrawn in 2004—and Avandia and Actos.

Next year the drug industry will likely pay the FDA's Center for Drug Evaluation and Research $400 million in user fees. "When you're getting paid directly from an industry you're supposed to be regulating, it takes quite a bit of edge out of the regulating," says Sidney Wolfe, M.D., director of health research for the consumer advocacy group Public Citizen, which often asks the FDA to withdraw drugs it considers risky. The group's publication Worst Pills, Best Pills currently lists 181 drugs it says "you should not use." Several of the brand-name drugs have been withdrawn from the market.

In February four former FDA heads said they'd prefer drug reviews to be funded by Congress rather than by user fees. Now, Grassley says of the drug companies' offer to pay for reviews, "We were suckers to take them up on it."

Experts say that the way complex new drugs are tested before approval—on relatively small groups of usually young and healthy people taking the test pill or a placebo—can't accurately forecast how safe they'll be over time for millions of patients who are older and may take several medications.

Yet the FDA devotes far more of its limited resources to approving new drugs than monitoring safety after they're on the market, according to two scathing reports from the Government Accountability Office and the Institute of Medicine in 2006. The IOM called on the agency to track the risks and benefits during a drug's entire lifetime on the market.

Congress has not yet given the FDA the authority to require drug companies to carry out post-marketing studies, and those conducted voluntarily are frequently not completed, the GAO says. In disputes over what action should be taken when safety problems arise, it is the FDA's approval office, which has closer ties to the industry, rather than the safety office that typically has the final say.

A Senate bill to reauthorize PDUFA, passed in early May, gives the FDA more ammunition to insist on follow-up studies. But an amendment giving the office of safety equal authority with the approvals office was defeated by one vote. The Avandia issue could push the provision into a House bill, Grassley says, but he doesn't underestimate drug industry opposition. "They don't want this sort of independence for post-marketing surveillance."

With increased use of prescription drugs, the FDA's workload has increased considerably in recent years, prompting AARP and many lawmakers to call for more funding for the agency.

There's also the issue of "transparency"—publishing all drug studies so scientists outside the FDA can review them and making the reasons for FDA decisions public. "Sometimes [drug safety] is complex, and there are pros and cons, and the data are not very solid," Wood says. "But at least we'd be able to see what's happening and why...and restore confidence in what FDA does."

What to do if you take Avandia:

• Don’t just stop taking medicine. If your blood sugar isn’t controlled, the risk of heart disease increases along with other risks.
• Ask your doctor: “What do you think is my risk on Avandia at this time?” That’s because the medical condition of your heart may have changed since you began taking it.
• If you’re not considered at risk but are uncomfortable with Avandia, ask about alternatives such as the older drug metformin.
• Consider insulin injections. Many people with type 2 diabetes become insulin-deficient with age. When used properly, insulin is safe and effective.