By Merrill Goozner
Last September an advisory panel voted 8-1 to recommend that the Food and Drug Administration approve a new drug for diabetes even though the risk of heart attack and stroke doubled among patients in clinical trials. The only cardiovascular expert on the committee didn't attend the panel's meeting because he had performed work for the drug manufacturer. But then, so had the committee's chairman, who did attend and in fact ran the meeting.

Some of the nation's leading cardiologists were upset by the recommendation. Writing in the Journal of the American Medical Association a few weeks later, they called on the FDA to reject muraglitazar because Bristol-Myers Squibb and Merck, its manufacturers, had failed to provide an accurate measure of the medication's risk.

"I'm increasingly concerned that these panels have become unbalanced," says Steven Nissen, M.D., of Ohio's Cleveland Clinic, a co-author of the JAMA article and former chair of the FDA's cardiovascular drugs advisory panel. "We have to make certain we have a balance of experts, [including] people who deal with the complications and side effects."

"There's too much bias toward bringing new treatments to market," adds Art Levin, director of the Center for Medical Consumers in New York and the consumer representative on the FDA Drug Safety and Risk Management Advisory Committee.

The FDA regulates companies that account for 25 percent of the U.S. economy. Its job is to protect the public from unsafe drugs, faulty medical devices and contaminated food. But 100 years after the birth of this federal agency, many doctors, consumer groups and lawmakers worry that the FDA is becoming less effective in carrying out its mission.

The hazy relationship between the FDA's advisory committees, such as the one for the diabetes drug, and the companies the agency regulates is just one issue raising concerns about the effectiveness of the FDA, which is still considered the gold standard among food and drug regulators around the world. Two other issues are a reported backlog of more than 800 generics awaiting approval and what the FDA acknowledges is the lax monitoring of drugs after they are approved and on the market.

"A lot of people are nervous about what's in their medicine cabinet, and for good reason," says Sen. Chuck Grassley, R-Iowa, a leading agency critic on Capitol Hill. "[The FDA] has become too cozy with the industry it regulates ... That's not a recipe for full trust and faith among consumers."

Acting FDA Commissioner Andrew von Eschenbach, M.D., the director of the National Cancer Institute who has been nominated to head the FDA permanently, insists the agency is working to protect the public. "We are making a tremendous commitment to the whole area of drug safety," he told Congress in March.

Serious questions about conflicts of interest at the FDA arose in 2004 when the painkiller Vioxx was taken off the market because it increased the risk of heart attack and stroke. Concerned that similar drugs might pose the same risk, the FDA convened a special advisory committee to evaluate the evidence. The agency almost always follows the advice of advisory panels, whose members are usually drawn from prominent medical institutions outside the FDA. Critics say most of the outside advisory panels include scientists with ties to the firms whose products are under agency review.

The panel that analyzed Vioxx, Celebrex and Bextra voted in February 2005 to keep them on the market, even though Vioxx had already been pulled. Only later did the media report that nearly a third of panel members had ties to makers of the drugs. Had their votes been excluded, the drugs would not have gotten a positive vote.

An FDA spokesman says advisory panelists are screened to "carefully weigh any potential financial interest with the need for essential scientific expertise" to protect public health.

"One of the conundrums," says Carl Peck, former director of the FDA's Center for Drug Evaluation who now heads the Center for Drug Development Science in Washington, is that the scientists "who are capable of making an informed decision are the very ones who typically are called on by drug companies and FDA to advise." He argues that limiting advisers to those who've never had research or consulting agreements with drugmakers could reduce the pool of qualified experts.

But Eric Topol, M.D., of Ohio's Case Western Reserve University disagrees. He says it's "essential for the 'jurors' to have no conflicts. There are many people who would qualify who have absolutely no ties to industry."

After the Vioxx decision, the FDA pledged to tighten its review process by creating an internal Drug Safety Oversight Board. The group has come under fire for meeting in secret, but the FDA says information from the companies involved is confidential. Peter Gross, M.D., outgoing head of the FDA's drug safety advisory committee, has urged more transparency, with "public representatives" named to the board.

The FDA gets more than 20 percent of its $2 billion annual budget from industry user fees, which are paid by companies seeking the FDA's OK to market new products. The fees, which account for nearly half of the new-drug office's budget, were mandated by law in 1992 to speed up the approval process by enabling the FDA to hire more reviewers.

"That's the problem," says Nissen of the Cleveland Clinic. "It would be smarter if we funded the FDA through public dollars. In terms of our national budget, it's trivial."

"I understand the importance of bringing new medications to market," he says. "But I just want to make sure we've appropriately balanced risk with benefit."

Meanwhile, just under 3 percent of agency funds is devoted to monitoring drug side effects. The FDA recently reported that drugmakers failed to begin two-thirds of post-approval studies it had requested. The agency has hired a consulting firm to assess the problem.

"The greatest flaw in our post-marketing system," Peck says, "is that it's voluntary by physicians and patients. This needs to be fixed."

He adds, "Everything needs improving, all the time."