Washington Report: A Warning Trend

Washington's new answer to drug safety concerns is more warnings and more disclosure of undigested data. But warnings can go too far. Haven't FDA's critics ever heard the story of the boy who cried wolf?
Apr 01, 2006


Jill Wechsler
The campaign against unsafe drugs is escalating on all sides. FDA is requesting postmarketing studies for just about every innovative new medicine—not just those receiving accelerated approval. FDA advisory committees are urging black box warnings at the least hint of adverse events. Legislation has been proposed to overhaul FDA oversight of drug safety and to require pharma companies to complete promised Phase IV studies. Meanwhile, members of Congress have been calling for more public disclosure of emerging safety issues.

Unfortunately, critics seem to be paying little attention to the possibility that "transparency" may confuse prescribers and patients, and curb access to effective treatments. An overly risk-averse FDA may be slow to bring new therapies to market. And more extensive preapproval studies will likely raise the already astronomical cost of drug development, without producing much useful information.

FDA is caught in the middle. If agency officials question the need for more safety warnings, they'll look like they're in the pharmaceutical industry's pocket. But if they demand heightened warnings on more and more drugs, they run the risk of teaching doctors and patients to ignore them. Getting the risk-benefit equation right is never easy, and it's getting harder.

Aggressive Advisors

Case in point: At its February meeting, FDA's Drug Safety and Risk Management Advisory Committee unexpectedly recommended black box warnings for medicines that treat attention deficit/hyperactivity disorder. Advocates of the move pointed out that patients taking similar drugs ran an increased risk for myocardial infarction and stroke—and that some one million adults (as well as four million children) now take these medicines. Although the vote was close (eight to seven) on the black box proposal, the panel was unanimous in recommending that MedGuides be distributed with these drugs.

For their part, FDA officials questioned whether the new warnings were justified by the evidence. At a post-meeting briefing, Robert Temple, director of the Office of Medical Policy, acknowledged that there are concerns about people with heart problems using these drugs. But FDA doesn't usually write a black box warning "without some pretty decent data," he said. Robert Laughren, director of the Division of Psychiatry Products, pointed out that overuse of the black box warning could both dilute its impact and limit access to needed treatment—as has occurred since black box warnings were added to antidepressants.

Congressional Scrutiny

More severe warnings will go on ADHD drugs, however, if Senator Charles Grassley (R-IA) has anything to say about it. Grassley, who chairs the Senate Finance Committee, has added FDA oversight to his committee's agenda. (Now that Medicare is paying for prescription drugs, Grassley says the panel is responsible for ensuring that taxpayers pay only for safe and effective medicines.) The committee has been probing FDA activities and drug safety, and Grassley backs legislation to strengthen FDA enforcement authority and to establish a new office to oversee drug safety, separate from the drug approval process.

A current Grassley target is supposedly lax FDA oversight of medical device safety. The committee recently issued a lengthy report criticizing the director of FDA's Center for Devices and Radiological Health (CDRH) for approving expanded use of Cyberonics' nerve-stimulation implant to treat persistent depression in addition to epileptic seizures, despite CDRH staff concerns about safety problems and weak efficacy data. Whether or not FDA made the right call, such public scrutiny will make agency officials even more reluctant to approve controversial applications in the future.

Cutting Both Ways

Politically inspired attacks on FDA regulatory decisions are not limited to over-prescribing of medications with hidden cardio risks. They also open the door for politicians to challenge the safety and effectiveness of birth control and other controversial therapies. Conservative Republicans have been calling for increased scrutiny of the abortifacient Mifeprex (mifepristone or RU-486), following reports of several deaths among women using the drug. Danco Laboratories has marketed the treatment since 2000 with black box warnings that highlight the need for careful administration and follow-up.