Thursday, May 31, 2007

F.D.A. Still Unsettled in Wake of New Questions

ROCKVILLE, Md., May 30 — When Dr. Andrew C. von Eschenbach took over the Food and Drug Administration in 2005, the agency had a crisis over drug approvals that had missed or ignored dangerous side effects in Vioxx, antidepressants and other prominent medications.
Dr. von Eschenbach promised improvements, and agency officials said they would no longer be caught flatfooted on drug safety.
But this month, The New England Journal of Medicine published a study suggesting that a major diabetes pill, Avandia, might increase the risk of heart attacks.
Concerns over that drug and others have led Republicans and Democrats in the House and the Senate to call for investigations. A House hearing is planned for June 6.
Dr. von Eschenbach said in a briefing on Wednesday that his agency needed to collaborate more closely with drug companies.
“The point is that we need to look at the role of the F.D.A. in being a bridge to the future, not a barrier to the future,” he said at his office here.
Responding to a suggestion that promoting collaborations with drug makers, including an effort to modernize human testing and find genetic markers to predict suffering from side effects, may not be politic, Dr. von Eschenbach said the agency was not working solely with pharmaceutical companies.
“It’s with everyone,” including government agencies and independent scientists, he said.
He defended the agency in the Avandia case, saying, “I believe we did it right with regard to Avandia.”
Hints of the heart risks from Avandia were, however, present from the beginning. The original trials, overseen by GlaxoSmithKline, the drug’s maker, showed that patients taking the drug had more than twice the rate of ischemic heart disease as recipients of placebos.
The medical reviewer for the F.D.A. expressed concerns, but in a further analysis decided that it was less of a problem.
The hearing next week may highlight the growing internal dissension between officials who approve drugs and those who track the safety of drugs after they have been approval. Tension between the groups has long been common, but in recent months it has erupted into sniping.
Congressional investigators said the safety group recommended months ago that the drug agency put its severest warning on Avandia. The review group, which holds sway, has not done so.
The sniping became public in an exchange at an advisory committee hearing last month on whether to approve a new arthritis drug.
On one side was Dr. David Graham, author of an internal report that found that Avandia substantially increased the risks of heart attack, findings similar to the medical journal’s report.
On the other, Dr. Robert J. Meyer, an office director in the drug review division, and his boss, Dr. John Jenkins, were in a group deciding against warning about the potential risks.
There was little chance that the advisory committee or the drug agency would approve the arthritis drug, Arcoxia, at the hearing.
Behind the scenes, agency officials were battling over Avandia. Dr. Graham told the committee that top agency officials had demanded an unreasonable level of certainty about a drug’s risks before agreeing to warn the public.
“They assume it’s safe,” Dr. Graham said of the top officials’ analyses of safety data. “Which is just looking at things all the way wrong.”
Dr. Jenkins said Dr. Graham’s “characterization of how we look at safety data is simply false.”
“We make our best informed judgment about what the regulatory action should be,” Dr. Jenkins added.
Senator Charles E. Grassley, Republican of Iowa, and others on Capitol Hill, say the rift between the approval office and the safety office means that the two must separate and that the safety group must have more power. Mr. Grassley proposed such a split in an amendment this month; it failed by one vote.
Top House staff members said the Avandia case had breathed new life into Mr. Grassley’s proposal, because the House will soon debate changing the drug agency.
Curt Furberg, a professor of public health sciences at Wake Forest and a co-author of the New England Journal of Medicine’s editorial on Avandia, said the agency remained broken.
“Safety is just not a high priority for them,” said Dr. Furberg, who serves on the F.D.A. Drug Safety and Risk Management Advisory Committee.

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