FDA Defends Handling of Vioxx Concerns

Congress is looking into whether the Food and Drug Administration (search) shirked its duty by ignoring safety concerns about Vioxx (search) raised by its own reviewers and outside scientists.

Hours before a Thursday hearing, the FDA (search) defended its oversight and attempted to paint the reviewer, who will be called to testify, as a maverick who did not follow agency protocol.

In many respects, the FDA finds itself, again, explaining its actions before congressional critics, much like it did when antidepressant safety concerns were raised.

This time, however, the agency's acting commissioner more aggressively attempted to set the agenda, citing the FDA's "well-documented and long-standing commitment to openness and transparency in its review of marketed drugs."

Lester Crawford's statement, sent by e-mail to reporters about 16 hours before the Senate Finance Committee's scheduled hearing on Vioxx, also said the FDA initiated and paid for reviews of Vioxx and antidepressants after those drugs had hit the market. "That is evidence the system is working," Crawford said.

Critics contend the agency ignored risks in both instances, then intimidated its own reviewers when they pointed to safety concerns.

In October, the FDA ordered that all antidepressants carry warnings that they "increase the risk of suicidal thinking and behavior" in children who take them. Vioxx's maker, Merck & Co. pulled the drug from the market on Sept. 30 after a study indicated the popular painkiller doubled the risk of heart attacks and stroke when taken for longer than 18 months.

The FDA's statement disturbed lawyer Andy Birchfield, who is evaluating thousands of potential cases against Merck on behalf of injured patients.

"How can they see that type of problem and look back and say 'We did everything right'?" Birchfield said. "When they're not willing to recognize mistakes, we have no hope for them voluntarily taking measures to correct the situation."

One of the witnesses set to appear before senators was David Graham, an FDA reviewer who concluded that risks posed by Vioxx were so high that patients should not use the drug.

Graham was lead author on a research project that studied the records of almost 1.4 million Kaiser Permanente patients, including 40,405 treated with Pfizer's Celebrex and 26,748 treated with Vioxx. The study found that high doses of Vioxx tripled risks of heart attacks and sudden cardiac death.

Vioxx was responsible for an additional 27,785 deaths from heart ailments from 1999 to 2003, Graham concluded.

He has told congressional investigators that superiors pressured him to soften his conclusions.

Crawford said in his statement that Graham "voluntarily chose to revise his conclusions, and he did so, in his own words, 'without compromising my deeply held convictions."'

Without identifying Graham by name, Crawford said the reviewer submitted his paper for publication in Lancet — a journal that sharply criticized the FDA — "without going through the long-established peer review and clearance process established for scientific papers submitted by FDA scientists."

The commissioner also addressed the case of a federal drug safety adviser who said the FDA had disinvited him from a February meeting on the risk of new generation painkillers, including Vioxx and Bextra.

Dr. Curt Furberg recently found that Bextra doubled the risk of heart and stroke among heart disease patients. He said last week that an FDA official told him he could no longer attend the advisory committee hearing after Furberg was quoted as saying Bextra was no different from Vioxx.

Crawford said it "was premature for any FDA official to suggest that Dr. Furberg could not participate in the upcoming meeting. A decision on Dr. Furberg's participation has not been made because all of the relevant information is not yet available," he said.

Furberg, in New Zealand through late December, was unavailable for comment Thursday.