Congress Seeks to Balance Drug Safety, Quick Approval

From 1993 to 2003, the average approval time for standard drugs fell from 22 to 14 months. For fast-tracked "priority" drugs it declined more steeply, from 13 months to six. This dramatically changed the United States from a country where new drugs came late to one where they came early. In the decade before the PDUFA, only about 8 percent of new prescription drugs became available first in the United States; now that number is about 50 percent.

The user-fee system nearly doubled the number of FDA workers reviewing new drugs, from about 1,300 in 1992 to 2,500 in 2004. Equally important, it changed the work culture at the agency.

The act laid out guidelines requiring that at least 90 percent of drug reviews be done within a specified time after an application was filed. It specified how quickly the agency had to respond to company requests for meetings with FDA reviewers. It allowed manufacturers to ask the FDA to look over their drug-testing protocols before the studies were done -- an option that by 2004 had added 346 meetings a year to the 2,132 regularly scheduled ones between the agency and the companies.

Although drug reviewers suffered no penalties if they missed these goals, they took them very seriously -- and consistently met them, FDA annual reports show.

The payoffs and the hazards of this more company-friendly FDA were revealed in two unusual studies published recently.

Tomas J. Philipson of the University of Chicago and four colleagues analyzed the economic and human effects of the first decade of the user-fee system.

They estimated that the speedier approvals yielded at least $11 billion in new profits for the industry -- an average of about $39 million for each new drug. Faster action also saved 180,000 to 310,000 years of life for patients -- a gain partially offset by up to 56,000 years lost to the harmful effects of drugs approved but later withdrawn for safety reasons.

The FDA touts the consumer payoff.

"Early access to safe and effective medicine is good for public health," Theresa Mullin, FDA assistant commissioner for planning, said in a recent interview. "For people with Parkinson's, with early Alzheimer's, with cancer, time is a luxury you just don't have."

On the other hand, Daniel Carpenter, a government professor at Harvard, has studied the potential effects of the time pressure that the PDUFA placed on the FDA.

He found that drugs approved in the two months before the deadlines were three to five times as likely to be taken off the market for safety reasons as drugs approved earlier in the cycle or after, when the agency missed the deadline.

"Our analyses suggest the [act's] clocks have dramatically changed the behavioral structure of the FDA review cycle," he wrote.