Congress Seeks to Balance Drug Safety, Quick Approval

Three drugs -- Vioxx, Ketek and Avandia -- are casting long shadows over the congressional debate on how to update and revise the 15-year-old system that has dramatically sped up the process of bringing prescription medicines to American consumers.

All three ran into problems after the Food and Drug Administration approved them for use. The problems ranged from thousands of heart attacks partly attributable to the painkiller Vioxx to a few cases of liver failure caused by the antibiotic Ketek. And the hazards of the diabetes drug Avandia are only now emerging.

Together, the three drugs epitomize what can happen when a new pharmaceutical moves from the small and orderly world of scientific testing to the big and messy world of everyday use. Many experts now hope that efforts to do a better job of identifying the "unexpected toxicities" in drugs that have reached medicine cabinets will get a boost from an unexpected source -- the Prescription Drug User Fee Act.

The act's chief purpose when it was passed in 1992 was to help drugs get through FDA review quicker and out to patients sooner. It did so by creating a "user fee" that a company must pay when it submits the mass of research and paperwork that the FDA reviews before approving or rejecting a drug. As Congress debates reauthorizing the user-fee law, it is considering several proposals that would raise the fees and devote a larger portion of them to "post-market surveillance" of drugs -- the regulatory equivalent of chasing the horses after they are out of the barn.

The debate touches not only on how much to spend on post-market surveillance but also on the user-fee system itself. Those fees now provide more than half of the money the FDA spends, mostly on salaries, to review new drugs. The agency wants to collect $393 million next year, $87 million more than this year.

In April, the Senate passed a huge FDA-related bill that included a reauthorization of the user fees for five more years. The House will consider numerous bills on the same subjects -- not only user fees for drugs and medical devices, but also incentives for testing drugs in children and long-range strategies for enhancing drug safety -- probably later this month.

Differences would have to be resolved in conference. But it seems likely that heavy reliance on user fees -- rather than appropriations by Congress -- will continue to be a key feature of pharmaceutical regulation.

"I am deeply disappointed in the way things are headed. This is our last chance to get it right before five more years go by," said Jerry Avorn, a Harvard Medical School physician and expert on drug safety.

Avorn says that not enough money is being spent on "pharmacovigilance" -- the ongoing study of drug safety -- and that the FDA's dependence on industry money may be corrupting it in subtle ways.

The user-fee act, which goes by the awkward acronym PDUFA, was born of attacks from two quarters.

Industry wanted faster action by the FDA so that its review of new drugs would consume as little as possible of the period in which a product is under patent. Companies were willing to pay the FDA to hire more people because quicker reviews might ultimately increase profits. At the same time that companies were complaining of the FDA's slowness, advocates for patients were lambasting the agency for insufficient urgency in making drugs -- particularly AIDS drugs -- available to sick or dying patients.

As a strategy for addressing those complaints, the law has been a huge success.