Originally created 07/11/98

Critics question FDA safety net



WASHINGTON -- Almost as many prescription drugs were yanked off the U.S. market in the past 10 months as were banned in the entire previous decade, a spate that has critics questioning if the Food and Drug Administration's safety nets are breaking down.

A senator has persuaded Congress' General Accounting Office to investigate whether the FDA -- under political pressure to speed approvals -- is doing enough to safeguard against risky medicines, or is passing drugs that once would have been held up for further study. One longtime FDA pharmacologist told The Associated Press that she just left the agency in frustration with pressure to skim over safety concerns.

The message was that "one should be approving things, not questioning problems that arise, and ... give the drug company the benefit of the doubt," said Elizabeth Barbehenn, who spent 13 years at FDA monitoring the safety of certain experimental drugs.

"The red flag is up," said consumer advocate Dr. Sidney Wolfe of Public Citizen, who noted experts had questioned some of the five recently banned medicines before they were ever sold. "Whoever is responsible for creating the attitude at the FDA that they have to approve drugs even with serious safety concerns is starting to see the bloody results."

Dr. Michael Friedman, FDA's acting commissioner, vehemently denies that outside pressure influences drug-safety decisions.

"What drives the agency is not political or commercial or any other interest short of scientific," said Friedman. "It is not a responsible position ... to suggest the agency would ... do anything less than our very best to make public health decisions."

The FDA appropriately approved the later-banned drugs because the full scope of side effects did not show up at first -- and the system worked by catching them as soon as they did appear, Friedman said.

Five drugs have been pulled off the market since September: The painkiller Duract for causing liver failure, including four deaths and eight liver transplants; the blood pressure drug Posicor, after 400 injuries and 24 deaths when it interacted dangerously with other medications; the diet drugs fenfluramine and Redux for damaging hearts; and the antihistamine Seldane, which interacted lethally with a long list of other drugs.

In the previous 10 years, the FDA had banned just six other drugs.

The FDA performs a complex balancing act: Getting the promising new drugs to desperately ill patients quickly, at the same time hunting the often subtle clues that signal which drugs will cause dangerous side effects.

Drugs are approved based on studies in a few hundred to a few thousand carefully chosen patients. That means rare problems may not emerge until tens of thousands of patients, or sicker ones, take them.

Over the past three years, Congress intensely pressured the once-backlogged FDA to speed approvals. Critics even accused FDA of killing patients by delaying potentially lifesaving therapies.

Attempts to force a drastic speedup ultimately failed. Still, by charging new fees to drug makers, FDA hired hundreds more reviewers and approved a record 92 unique new drugs in 1996 and 1997, up from 50 the previous two years.

Faster approval of lifesaving therapies is good, Wolfe said -- but just 20 percent of FDA-approved products are medical breakthroughs.

Most instead are "me-too" drugs like the just-banned Duract and Posicor. Wolfe lists at least 18 similar painkillers and 30 blood-pressure alternatives, questioning why the two were approved last year. The FDA knew that Duract, for example, caused serious liver damage if taken for longer than 10 days.

And there's a separate problem: How to inform doctors of the side effects that come with every drug.

Some 2 million Americans are hospitalized annually for side effects, and 100,000 die, Thomas J. Moore, a researcher at George Washington University, reported this spring.

The FDA has to upgrade safety warnings on more than 20 drugs every month.

But doctors aren't required to report side effects to FDA so it can warn the public, and many don't. The agency has only about 80 employees to monitor more than 3,000 prescription drugs, but is working to improve surveillance, Friedman said.

Nor can the FDA force doctors to heed warnings. Duract, the painkiller, had to be banned because doctors ignored FDA's warning not to prescribe it for longer than 10 days, Friedman said. "If these products were used as prescribed, many of them would still be on the market."

Sen. Edward Kennedy, D-Mass., asked the GAO to quickly investigate how well the FDA handles drug safety and side effects. Republicans, too, are making inquiries, but agree with Friedman that the drug bans actually may mean the system is working by detecting trouble.

There's no easy answer, because every drug approved is ultimately a judgment call, stressed Moore. He wants Congress to establish a scientific panel that judges how the FDA handles drug controversies, much as the National Transportation Safety Board investigates plane crashes.

"How safe does a drug have to be? There is no simple answer," Moore said. "It is a question of getting the right balance, of learning from our mistakes, which is not happening now."