Millions of Americans unknowingly risk rare but serious drug side effects, Consumer Reports says.

In its January 2006 issue, the independent consumer magazine points to a dozen common prescription drugs linked to serious risks — including death. These risks, the article says, were "undetected or underestimated when the FDA approved them for use."

The issue isn't these 12 drugs. For people who need them, their benefits outweigh their risks. What's flawed is the U.S. drug safety system, says Marvin M. Lipman, MD, chief medical advisor for Consumers Union and emeritus professor of medicine at New York Medical College, Valhalla.

"This is a report that criticizes not only the preapproval process, but also the postapproval surveillance system," Lipman tells WebMD.

System Geared for Approval

Once upon a time, the FDA was very slow to approve new drugs. That changed in the early '90s, when Congress passed the Prescription Drug User Fee Act (PDUFA). The law gave the FDA deadlines for making approval decisions. In return, it charged drug companies fees used to hire new drug reviewers.

The Consumer Reports article quotes a former FDA reviewer as saying that the tight deadlines were frustrating. Indeed, a 2003 HHS survey found that 20 percent of FDA reviewers said they felt pressured to recommend approval despite reservations.

"The relationship of the FDA to the pharmaceutical industry has to be examined very closely," Lipman says. "Under the PDUFA law, a lot of money is paid by the drug companies to have their drugs reviewed. There is something inherently bad about that. It doesn't smell right."

Drug Industry Reaction

Jeff Trewhitt, a spokesman for the Pharmaceutical Research and Manufacturers of America (PhRMA), says PDUFA fees improve drug safety.

"PDUFA has raised hundreds of millions of dollars for FDA in a time when Congress has approved only stagnant funding, even though regulators' duties have expanded dramatically," Trewhitt tells WebMD. "PDUFA money is also being used to increase staffing in the Office of Drug Safety at FDA. It's recently allowed FDA to double the number of safety officers from 100 to 206 officers."

And Trewhitt notes that fewer than 3 percent of drugs are withdrawn from the market due to safety concerns — a rate that hasn't changed since PDUFA took effect.

Laurence B. Gardner, MD, chairman of the department of medicine at the University of Miami Miller School of Medicine, agrees with most of the points made by the Consumer Reports article. But he says the FDA's preapproval process isn't the problem.

"Consumer Reports implies that people at the FDA rush approvals through and don't look at safety data," Gardner tells WebMD. "But we are still the safest country in the world when it comes to drug approval. That being said, there are a lot of issues with our health care system. And current regulations don't protect the consumer."

After Drug Approval: Patient Beware

When the FDA approves a drug, it sometimes asks the manufacturer to conduct further safety studies. Consumer Reports notes that in February 2005, companies agreed to 1,191 such studies. Yet as of September 2005, more than two-thirds of the studies were still "pending."

The most important drug-safety experiment comes in the years following drug approval. The subjects of this study: consumers who take the drug.

Preapproval studies enroll no more than a few thousand people — usually healthier people than many of those who will take the drug after approval. And the studies usually last only a few months. Rare side effects, problems for people with multiple conditions taking multiple other drugs, and long-term side effects can only be seen in the years following approval.

And that, Lipman says, is where the U.S. system breaks down. Doctors are supposed to report any side effects that happen. But because there is no reliable system — and, Gardner says, because these reports aren't easy to file — only a small fraction of side effects actually get reported.

Compounding this problem, Lipman says, is direct-to-consumer advertising. Ads heavily promote new drugs. Yet there's a drug risk associated with every drug benefit. And the Consumer Reports article states the ads stress benefits but don't adequately identify risks.

"It is impossible to monitor all the ads that are out there," Lipman says. "And more ludicrous, the ad goes into the media, and it takes FDA three to six months to catch up with the ad. By that time, the damage is done. You need an approval system before, not after the ads hit the media. They should submit copy for vetting by the FDA, and the FDA needs resources for this. They don't have the personnel or the money."

The Consumer Reports article notes that PhRMA in August 2005 announced guiding principles for direct-to-consumer ads, including a wait before advertising new drugs. As of November, the article reports, most of PhRMA's 33 members had signed on.

Independent Drug Safety Board Needed?

Currently, the FDA's drug-safety office is one of 12 subgroups reporting to the director of the FDA's Center for Drug Evaluation. It's been lacking a permanent chief for some time.

Lipman says there should be a drug safety office — with regulatory teeth — outside the FDA.

"What is really needed, in our opinion, is an independent office of drug safety: nonbiased safety experts not part of either the pharmaceutical industry or the FDA," he says. "The same people can't be responsible for drug approval and drug safety. It just makes it that much harder for a drug to be withdrawn by the people who approved it."

Gardner isn't so sure. He thinks that a drug safety office would be no better than the expert advisory panels that currently advise the FDA. Instead of a new layer of bureaucracy, he would like to see more power given to these panels of experts.

PhRMA's Trewhitt doesn't see the need for any of this. "Simply put, the FDA still has the world's best drug safety record," he says.

Institute of Medicineto the Rescue

Lipman, Gardner, and Trewhitt all praise one thing about the FDA. The agency already has asked for help. Last year, it turned to the independent Institute of Medicine (IOM) for advice. An IOM committee has since been holding hearings. Its recommendations are expected in July 2006.

"The FDA has asked the IOM to thoroughly investigate the drug safety system," Trewhitt says. "It would behoove us to wait to see the results."

Lipman says it's already time for Congress to act.

"We are getting to where this is a problem for our government," he says. "There have to be some bills written that would address some of these problems and that would create a better workforce for the FDA, and that would give them more monetary resources so they don't have to rely on pharmaceutical company fees to process new drugs. Basically the buck passes back to our Congress."

Gardner says the problem goes far beyond the FDA. The real issue, he says, is health care in America.

"Our health care system is in real trouble," Gardner says. "This is an example of a real problem where we don't have the politics yet to create a solution."

Those 12 Drugs

The Consumer Reports article lists 12 drugs as examples of safety-system failures.

"These drugs are just examples," Lipman says. "There are bound to be others. Even a perfect safety system could never detect every problem of every drug."

The drugs are:

—Celebrex

—Estrogen, either alone (Premarin and others) or with progestin (Prempro and others)

—Accutane

—Ovide

—Depo-Provera

—Lariam

—Crestor

—Serevent

—Meridia

—SSRI antidepressants and other antidepressants

—Zelnorm

—Topical immunosuppressants such as Elidel and Protopic

Do not stop taking these drugs if you're using them, Consumer Reports warns. The drugs are helpful for people for whom the benefits outweigh the risks.

"These are important drugs. They are very useful drugs," Lipman says. "But in many cases they are not the only drug for the condition. And the patient should know that by taking one of these drugs there is a certain inherent risk, and the patient should be aware of this risk."

Lipman advises patients using these drugs to talk with their doctors about whether there is another drug that can be used with less risk. And all patients taking any drug should be aware of possible side effects and should tell their doctors about any ill effects — even those not listed on the label.

By Daniel J. DeNoon, reviewed by Brunilda Nazario, MD

SOURCES: Consumer Reports, January 2006;pp 34-39. WebMD Feature: "How Safe Are America's Medicines?" FDA web site. IOM web site. PhRMA web site. Marvin M. Lipman, MD, chief medical advisor, Consumers Union; emeritus professor of medicine, New York Medical College, Valhalla. Jeff Trewhitt, spokesman, Pharmaceutical Research and Manufacturers of America (PhRMA). Laurence B. Gardner, MD, vice dean, medical school, and chairman, department of medicine, University of Miami Miller School of Medicine.