Congress Seeks to Balance Drug Safety, Quick Approval

Few doubt, though, that even the most carefully tested drugs can produce surprises. That is true both when the problems they cause are extremely rare (such as spontaneous liver failure with Ketek) or very common (such as heart attacks with Vioxx, and possibly with Avandia). Either way, the problems are hard to detect.

"Many of the adverse reactions that we care about are not recognized as adverse reactions most of the time," said Richard Platt, a researcher at Brigham and Women's Hospital in Boston. Traditionally, the FDA has relied on spontaneous reports from many doctors, or on the sharp eyes of a few, to catch the bad actors. The latter occurred 10 years ago when several physicians at the Mayo Clinic noticed rare heart-valve lesions in women taking the diet-drug combination fen-phen.

Now, many experts -- Platt is one of the leaders -- believe large databases maintained by Medicare and HMOs can be "interrogated" by sophisticated computer programs to identify problems far earlier than if regulators just wait for reports to trickle in. A report last year by the National Academies' Institute of Medicine pushed for more such studies, among other drug-safety strategies.

Such database analyses helped reveal the hazards of Vioxx, which got fast-track approval in 1999 because it caused less intestinal bleeding -- and thus appeared safer -- than other nonsteroidal painkillers.

Five months before Merck voluntarily pulled the drug from the market in September 2004, a research team that included Avorn examined the experience of 54,000 elderly enrollees in two large pharmacy benefits programs. They found that people taking Vioxx had more heart attacks. A later study by Swiss researchers concluded that if another strategy called cumulative meta-analysis had been used to study the totality of research on Vioxx, the drug's risks could have been recognized by early 2001.

Today, nearly everyone agrees that more attention should be paid to tracking the safety of drugs already in use.

Originally, user-fee money could not legally be spent for that purpose. Now it can be, but only to study a drug's performance during its first three years on the market. Even that restriction would be lifted under the current proposals.

Meanwhile, the FDA increased the number of employees doing post-market surveillance from 62 to 96, with at least 80 more to be added next year. Bills in both the House and the Senate would more than double -- from $30 million to about $75 million -- the amount of user-fee money for post-market review of drugs.

But many people think that is not nearly enough for a country where the average 65-year-old takes six prescription medicines, $180 billion is spent on those drugs and manufacturers spend $12 billion advertising them.