A BETTER SAFETY NET

First researchers disclosed fears that popular antidepressants might increase the risk of teen suicide. Then studies linked widely prescribed arthritis painkillers like Vioxx and Celebrex to heart attacks and strokes. And government officials warned that two eczema creams used by 15 million Americans could boost the risk of certain cancers. Just open the newspaper and odds are good you'll be confronted with yet another safety scare over a prescription drug--perhaps even one in your medicine cabinet. On its Web site, the watchdog group Public Citizen now lists nearly 200 government-approved drugs that its experts believe are too dangerous to use. In dramatic testimony before Congress last fall, whistle-blower Dr. David Graham, a reviewer in the Food and Drug Administration's Office of Drug Safety, said Americans are "virtually defenseless" against unsafe drugs, and called regulators "incapable of protecting America against another Vioxx."

That steady drumbeat of bad news has left patients confused, drug companies defensive and government officials at odds over how to fix the problem. Critics cite a long list of complaints: the FDA is too cozy with the industry it's supposed to regulate; it devotes more resources to approving new drugs than to monitoring the safety of those already on the market; science doesn't play enough of a role in the approval process itself. The problems are exacerbated, they say, by a flood of direct-to-consumer advertising that drives up drug sales too quickly, boosting the number of patients as well as side effects. And without strong leadership--the FDA has lacked a permanent director for more than a year--the agency has been hard pressed to institute reforms.

The FDA readily acknowledges it cannot guarantee drug safety. Although drugmakers are required to test their products extensively before they're greenlighted for pharmacy shelves, some problems don't become obvious until many thousands of patients take the drug. And even the safest drugs have dangerous side effects. The problem costs billions annually and, says Dr. Janet Woodcock, the FDA's acting deputy commissioner for operations, is perhaps the country's fifth leading cause of death. "You can't know everything about a drug before it gets on the market," she says.

Even so, officials are eager to stem the flow of bad news and restore public confidence. Health and Human Services Secretary Michael Leavitt, who earlier this year took the helm at the agency that oversees the FDA, has promised both "more oversight and more openness." Drug companies are also anxious to reassure consumers, but caution regulators not to go too far. "If these new drugs are going to reach patients who need them, you can't make the process too cumbersome," says Billy Tauzin, president of the Pharmaceutical Research and Manufacturers of America, the industry's lobbying group. The FDA has proposed some fixes it hopes will strike the right balance. Lawmakers and watchdog groups have suggested others. Although many changes are still up for debate, here are seven key areas to watch.

Scientific approach Critics say the FDA doesn't focus enough on whether the benefits of new drugs truly outweigh their risks. "Within the agency, there's not enough respect for the scientific process," says Sen. Charles Grassley of Iowa, one of the FDA's toughest critics on Capitol Hill. Some of the FDA's decision-making is hobbled by the fact that drug companies don't always provide research data that contradict their claims, says Dr. Bruce Psaty, professor of medicine and epidemiology at the University of Washington. Because today's blockbuster drugs are taken by millions of patients, reformers are lobbying for longer, more-extensive clinical trials before the drugs hit the market. "For drugs that are going to have wide exposure, there should be an even greater safety threshold," says the FDA's Graham. Critics also suggest requiring more post-marketing studies.

The structure of the FDA Although the FDA office that approves new drugs has more than 1,000 employees, the Office of Drug Safety has just 100. That means the emphasis is on pushing drugs through the pipeline, not on monitoring them once they reach the market. To change that, the FDA has proposed a drug-safety oversight board within the same FDA division that approves new drugs. Critics say that's not enough. As it is now, the current Office of Drug Safety "gets tremendous pressure from the office of new drugs who don't want egg on their face" from criticism of drugs they approved, Grassley says. He has won support from public-interest groups for his plan to create an independent Center for Post-Market Drug Evaluation and Research, reporting directly to the FDA commissioner. Other critics want a safety board outside FDA altogether.

Enforcement power Unless the HHS secretary declares an imminent health risk, the FDA cannot force a drugmaker to pull its medicine off the market. A proposal by Senator Grassley and Connecticut Sen. Chris Dodd would give new powers to the director of an FDA Center for Post-Market Drug Evaluation and Research. The director could require drugmakers to conduct clinical trials after the drug is approved. If safety concerns arise, the director would also be able to order label changes or withdraw the drug's approval altogether.

The FDA's view of drugmakers In the early 1990s, at the height of the AIDS epidemic, the FDA was criticized for being too cautious and slow about approving life-saving medicines. Congress decided to give the FDA more resources, not with tax dollars but by requiring drug companies to pay the administration a "user fee." In return, the agency promised a faster turnaround for new drug applications. Approval times dropped sharply. Critics charge it also created an FDA culture that sees drug companies as "clients," not an industry to be regulated. "Particularly in the last 10 to 15 years, the FDA has capitulated to the drug industry," says Dr. Sidney Wolfe, director of Public Citizen's Health Research Group. Grassley's plan would provide separate federal funds for post-marketing surveillance. Former FDA hands like Dr. David Kessler agree that's a good idea. "The pendulum needs to swing back so it's not just about getting drugs reviewed on time," he says.

Drug ads Critics say extensive advertising of new drugs fuels problems by exposing many millions of patients to their side effects within a short time frame. But limiting drug ads would probably violate the First Amendment. "We're in a free-speech area," says drug lobbyist Tauzin. Grassley's plan would require drugmakers to submit ads to the FDA for approval; it also calls for disclosing more risks and benefits to patients. In an effort to pre-empt a government crackdown, drugmakers plan to adopt their own ad standards this summer.

More transparency Traditionally, the FDA has kept its investigations under wraps until it reached a firm conclusion. No more. In February, Acting FDA Commissioner Lester Crawford promised to take more information about drug risks and benefits directly to consumers. Grassley has also submitted legislation that would make all the results of clinical trials publicly available.

Scientific advances Electronic prescribing will make it easier to get warning information into doctors' hands in real time. And electronic patient records will allow health officials to track adverse events more easily. But the biggest changes may come in pre-marketing studies, says the FDA's Woodcock. Advances in personalized medicine will allow doctors to identify individuals who are genetically vulnerable to a drug's side effects. Until then, policymakers will have to find other ways to keep Americans feeling safe about reaching into their medicine cabinets.

A BETTER SAFETY NET | News