In the U.S. drug industry, it often takes a disaster to bring change. Not until thousands of European babies were deformed by thalidomide in the late 1950s and early 1960s did Congress raise standards for approvals. Now the Food & Drug Administration and Congress are grappling with what FDA whistle-blower David Graham says "may be the single greatest drug-safety catastrophe in the history of this country" -- the use by millions of people of a painkiller, Merck & Co.'s (MRK) Vioxx, that raises the risk of heart attacks. "It is a shame that something bad had to happen," says Dr. Albert I. Wertheimer, director of Temple University School of Pharmacy's Center for Pharmaceutical Health Services Research, "but this is a wake-up call."
Still, that call may not be fully heeded in Washington, where the powerful pharmaceutical industry will oppose serious reforms. That would be a mistake. Congress and the Bush Administration should legislate changes long advocated by safety experts, such as better clinical trials before drug approvals and stronger oversight after drugs are on the market.
The problem is that not enough is known about the benefits and risks of new drugs. Congress made this gap more difficult to address in the early 1990s by requiring faster FDA approvals, funded by industry dollars. Before that, drugs typically hit the market first in Europe, so the FDA had a chance to learn from data collected abroad before deciding to approve a drug here. Now that approvals are swifter, there's greater need to study and monitor new drugs more closely. Key steps:
BETTER PRE-APPROVAL CLINICAL TRIALS. "We have to demand more of drug companies," says Dr. Jerry Avorn, associate professor at Harvard Medical School and author of Powerful Medicines: The Benefits, Risks, and Costs of Prescription Drugs. A typical months-long trial with 3,000 carefully selected patients is unlikely to spot problems that show up only with longer-term use by more patients. Merck's original Vioxx trials should have been longer, larger, and more representative of the general population.
These changes don't have to be costly. Modern statistical tools and trial designs could yield more information for a given cost, adds Dr. Raymond L. Woosley, vice-president for health sciences at the University of Arizona College of Medicine.
MORE RIGOROUS POST-APPROVAL MONITORING. There's always a balance between getting drugs to patients quickly and studying medicines long enough to learn about side effects. In pre-approval testing "it is very difficult to pick up infrequent effects," says Dr. Steven Galson, acting director of the FDA's Center for Drug Evaluation & Research. That's why the FDA must beef up its post-marketing oversight. The agency could make mandatory doctors' reports of cases where patients appear to be harmed; now they're voluntary and haphazard. The FDA should also require companies to track what happens to the first 100,000 or 200,000 patients who get a new drug. And it should demand more clinical trials when problems are suspected.
The FDA approves some drugs on the condition that companies do follow-up studies. But two-thirds of the time companies fail to do them. Congress should give the agency the power to levy fines big enough to give drugmakers the incentive to actively pursue needed follow-up studies.
BOOST DRUG-SAFETY EXECS' CLOUT. The same FDA division that approves drugs also decides whether to take a drug off the market. But "reviewers don't like to admit they made a mistake," explains a congressional staffer. The result: It takes too long for the FDA to add restrictions or pull drugs. The agency's Office of Drug Safety needs more resources and more power to make these key decisions.
While it ponders these steps, Congress could also consider deeper questions. Do Big Pharma's dollars for drug reviews make the agency too beholden to the industry? Do direct-to-consumer ads encourage people to take drugs they don't need? It's tragic that thousands of Vioxx users may have died. But their deaths should lessen the chances of similar disasters.
By John Carey