Changes will ensure drug safety, FDA says

WASHINGTON —  The Food and Drug Administration pledged Tuesday to make major changes in the nation’s drug safety system, responding to a blue-ribbon panel that last fall found the agency’s priorities skewed toward approving new medications without adequate follow-up to identify rare but risky side effects.

FDA Commissioner Andrew C. von Eschenbach said the improvements would help the agency regain the “trust and confidence” of doctors and patients after a series of highly publicized safety lapses, including the withdrawal from the market of Vioxx, a previously approved and popular painkiller found to cause heart attacks.

But the FDA’s internal fixes stopped short of addressing key issues such as increased funding and broad new legal powers for the drug safety program -- reforms that depend on congressional action that may come this year. And some critics said the agency had not done enough to bring safety officials into the drug approval process.

Von Eschenbach conceded that more remained to be done, saying, “The initiatives we announce today are not the whole story, and they are not the final chapter in the story.”

The changes recognized the need to address safety over the entire lifecycle of a drug, from development to use by patients. They included measures to improve the scientific underpinnings of the safety system, increase monitoring for hazardous side effects, expand communication with patients and doctors, and address long-standing turf battles among FDA scientists that have gotten in the way of alerting the public to safety problems.

A pilot program also will be established to assess the safety record of new drugs 18 months after approval. It will be tried initially with a small number of medications, and results will be reported to the public.

Consumer groups dismissed the FDA’s initiative as too little, too late, but members of the panel of medical, legal and policy experts that spent more than a year investigating the drug safety program called it a respectable first step.

“It was a thoughtful and engaged response,” said Dr. Bruce M. Psaty, a professor of medicine and epidemiology at the University of Washington in Seattle and a member of the panel that studied shortcomings in the FDA’s safety program.

“It looks like they are launching a number of initiatives to address drug safety. Many of them are new, so the degree to which they will improve safety remains to be seen, but I think it’s a fairly comprehensive response,” he said.

The panel’s head, Sheila Burke, a former Republican Senate staffer who is now chief operating officer of the Smithsonian, took a tougher line. “I would have wanted to see more formal involvement of the safety staff in the drug development process,” she said.

Nonetheless, she said, “I think they are serious about trying to make some progress.”

The committee she led was sponsored by the Institute of Medicine, part of the National Academies that provide scientific, engineering and medical advice to the government. Convened at the FDA’s request, the panel issued a scathing report in September that seems to have chastened agency leaders.

Concerns about the safety of newly approved medications have been building for years. But they gained national attention in fall 2004 when Merck withdrew the blockbuster painkiller Vioxx, after company-funded studies confirmed heart attack risks that safety experts inside the FDA bureaucracy had unsuccessfully tried to warn about.

Testimony later at a congressional hearing showed that agency managers had dismissed their own experts’ warnings.

Tuesday’s announcement marked the second time in two years that the FDA had pledged to fix the drug safety system. Early in 2005, the agency set up an internal drug safety oversight board. But partly because the board meets in secret, its effects have been hard to gauge.

Some of the improvements announced Tuesday would require congressional approval to increase industry user fees, which would finance new safety initiatives.

Some of those initiatives will apply to drugs in development and after approval. Others attempt to resolve long-standing communication problems within the FDA, and between the agency and the public.

In the development phase, the FDA said it was working on new tests that might predict early on whether a drug would be toxic to humans. It has launched a research program to help identify the potential heart and stroke risks of medications, and is working with the National Institutes of Health to develop a computer model that could indicate a drug’s potential to cause liver damage -- a common risk.

It also is looking at how the burgeoning field of genetic research might aid drug safety.

Drugs in development are tested on several hundred or a few thousand human subjects. But rare side effects may emerge only after tens of thousands of patients have taken a medication. Many academic experts think new drugs should be considered “experimental” for the first two or three years after they are approved for marketing.

Indeed, the advisory panel recommended a special caution label for new medications, and restrictions on advertising.

To increase detection of unexpected side effects during the early years, the FDA announced several improvements to its drug safety monitoring system.

The agency said it would modernize its “adverse events” database -- which now captures only a small fraction of problems -- to make it easier for researchers to recognize that something was going wrong. The FDA also said it was teaming up with Veterans Affairs and Medicare to share extensive information that those agencies collect on doctors’ prescribing patterns and their patients’ outcomes.

And it is proposing the creation of a Sentinel Network that would coordinate private and government vigilance of drug safety problems.

Finally, the FDA said it would improve communication among its own scientists, as well as with doctors and patients. Agency officials said they would redouble efforts to find ways to resolve disputes between scientists who approve drugs and those who act as safety watchdogs.

“We need to improve the way scientific disagreements are handled and resolved,” said Dr. Steven K. Galson, director of the agency’s Center for Drug Evaluation and Research.

*

ricardo.alonso-zaldivar@latimes.com