FDA reviewers urge action to fix drug safety

WASHINGTON (Reuters) - U.S. lawmakers need to take steps to fix a Food and Drug Administration culture that discourages dissent about the risks of prescription drugs, current and former FDA reviewers told Congress on Tuesday.

A hearing on the FDA's oversight of drug safety focused largely on the agency's handling of a Sanofi-Aventis antibiotic, Ketek, that was linked to liver failure.

Dr. David Ross, a lead FDA safety reviewer for Ketek, said he left the agency last year after managers suppressed his and others' concerns about Ketek's risks and fraud in a key study.

"Without significant changes to our drug safety system and FDA, we are certain to see more Keteks," Ross told a subcommittee of the U.S. House of Representatives Energy and Commerce.

The FDA withdrew Ketek's approval for sinusitis and bronchitis on Monday because officials felt the drug was too risky for treating those relatively mild infections. Sanofi can sell Ketek to treat pneumonia.

Concerns about Ketek arose a year ago after reports of severe liver damage and death in some users. The drug was approved for sale in 2004 despite an investigation that found a safety study was tainted by fraud.

FDA whistle-blower David Graham, who told Congress in 2004 that the agency was unable to protect patients from dangerous drugs such as Merck & Co Inc.'s withdrawn arthritis pill Vioxx, said the agency had failed to fix its problems.

"I am here to tell you our nation is still at risk," said Graham, an associate director in the FDA office that monitors the side effects of drugs after they are on the market.

Graham urged lawmakers to scrutinize the FDA's oversight of risks of weight gain and diabetes from Eli Lilly and Co.'s schizophrenia drug Zyprexa. He also said he felt Congress should examine the widespread prescribing of other antipsychotic drugs in nursing homes.

Lilly, in a statement, said it worked with regulators to update Zyprexa's label with side effect information. The association with weight gain is not proof the medicine caused diabetes, the company said.

"Treating physicians have been kept fully aware of the risks associated with Zyprexa," Lilly said.

At the hearing, lawmakers discussed various measures to improve the FDA's monitoring of drug safety. Some suggested the creation of a more independent office to monitor side effects after approval, while others want to give the FDA more power to force drug makers to complete post-approval studies.

Committee members said they were concerned about how the FDA handled risks with Ketek, Vioxx and antidepressants made by several companies.

"With each of these drugs, it appears that the FDA is not seriously questioning whether the risks outweigh the benefits of the new drug," said Rep. Bart Stupak, a Michigan Democrat, who chairs the committee's subcommittee on oversight and investigations.

"One must ask, if the FDA is not protecting its client, the American people, whose interest is being protected?" Stupak said.

Republicans complained that neither the FDA nor Sanofi were invited to testify at the hearing. Stupak said they would be asked to speak at a later date.

Sanofi's actions also came under scrutiny. Ann Marie Cisneros, who was working for a company that monitored the tainted Ketek safety study, testified that the French drugmaker was aware of problems at one study site. The researcher at that site is now in prison for fraud.

Sanofi spokeswoman Lisa Kennedy, in an e-mail to Reuters, denied the company knew of the fraud at the time.

"We strongly object to that characterization," she said, adding that the company had acted "in good faith" and cooperated with investigations.

In a statement, the FDA said it has taken steps to strengthen drug safety monitoring. The agency also said it welcomed "the vigorous exchange of diverse and differing opinions" among scientists and had a dispute resolution process for staff to challenge decisions.

The FDA added it "shares Congress' commitment to drug safety issues."

(Additional reporting by Susan Heavey)