FDA Official Says Lessons Have Been Learned From Rezulin
Dr. Janet Woodcock delivers a mixed post-mortem of the diabetes pill Rezulin.
She faults many practicing physicians who failed to monitor Rezulin patients for signs of liver damage, as recommended by the Food and Drug Administration.
But Woodcock concedes that strict adherence to the recommended monitoring could not have reliably shielded patients from liver failure.
Woodcock, the FDA’s director of drug evaluation, said the agency’s objective in keeping Rezulin on the market for 29 months following the first reported liver failure deaths was to empower doctors to make their own, informed judgments.
“It wasn’t that people were compelled to prescribe this drug,” Woodcock said in an interview Thursday. “People could also choose not to take the drug. [Doctors and patients] have to make choices. And we at the FDA want them to be as informed as possible.”
Fewer than 1% of patients taking Rezulin for four months or longer followed the liver-monitoring recommendations, the FDA’s senior epidemiologist, Dr. David J. Graham, reported publicly in March 1999. Graham also warned that, because Rezulin caused liver failure so suddenly, the FDA’s monitoring would fail to protect patients in 75% of the cases he studied.
Woodcock, asked if her confidence was shaken by the liver failures and deaths of two Rezulin patients who were monitored in the strict setting of clinical trials in May 1998 and December 1998, said:
“It was disappointing. I think there was never a belief that monthly liver monitoring would be a panacea [that] could prevent all liver failure episodes. . . . We didn’t make any assurances or have any expectation that [it] would be completely protective.”
What percentage of liver failures had Woodcock thought the monitoring would prevent?
“We didn’t know,” she said.
Woodcock’s top deputy, Dr. Murray M. “Mac” Lumpkin, conceded that the FDA had no proof that monitoring would save Rezulin patients from liver failure.
“It’s one of the things that you have to learn with each of the drugs as you go along,” he said. “I think it’s one of the things that we continue to learn.”
FDA officials often cited monitoring as the means by which Rezulin patients could best avoid liver failure. Referring on Dec. 1, 1997, to three new deaths, the FDA said that the fatalities “occurred in patients treated before the stronger label warning and recommendation for liver [monitoring] took effect.”
About a year later, on Dec. 23, 1998, Woodcock was asked on ABC’s “Nightline” why she favored keeping Rezulin on the U.S. market after it had been withdrawn in Britain.
“We feel that the institution of the extra liver-test monitoring will render the drug safer,” she responded.
Woodcock said Thursday that her long-held view that Rezulin’s benefits in lowering blood-sugar levels had outweighed its risks stemmed from “a very difficult calculus.”
The rise and fall of Rezulin, Woodcock said, has taught the FDA to be more wary of whether liver monitoring or other recommendations in a drug’s labeling can make the product safer.
“The Rezulin experience made us, as an agency, more aware of the limitations of the use of the label to convey key information on safety.”
She added: “We have learned something from that experience. We’ve learned something we didn’t really know, fully, before.”
