REZULIN: Fast Approval Raises Questions About FDA Process
In the wake of the FDA's decision to yank Rezulin off the market, questions have been raised concerning the drug's swift approval as well as fast approval for other medications that "do not promise lifesaving benefits," the Los Angeles Times reports. The FDA pulled Rezulin off the market Tuesday after linking it to at least 90 liver failures, including 63 deaths and seven nonfatal organ transplants. FDA officials maintain that before withdrawing Rezulin, they waited to test the safety of two similar medications -- Avandia and Actos -- and had overseen four safety-labeling changes from fall 1997 to June 1999 for Rezulin. Dr. Janet Woodcock, director of the FDA's drug evaluation center, said that the labeling changes "were what we could do to manage the risk, under the circumstances."
Warning Signs from the Beginning
Often, the FDA and physicians "are unable to discern a dangerous side effect until after a medication has been tested in clinical trials and is put into mass circulation," but some experts argue that in the case of Rezulin, "warning signs were there from the beginning." Dr. John Gueriguian, the first FDA medical officer to examine Rezulin, opposed a fast-track review of the drug at an internal meeting in 1996 and Dr. David Graham, the FDA's senior epidemiologist, called Rezulin "one of the most dangerous drugs on the market," adding that there was no way to protect Rezulin users from liver failure. The FDA did not heed those doctors' warnings (Willman/Anderson, 3/23). Dr. Anne Peters, a University of California-Los Angeles endocrinologist who tested the drug in patients before its approval, said that initial abnormally high test readings "should have acted as a red flag" to the FDA and manufacturer Parke-Davis. But Dr. John Jenkins, director of a drug evaluation office for the FDA, said, "All drugs have risk. Some we don't learn about until after the drug is approved," adding that some cases of liver failure occurred "so suddenly that even monthly monitoring could not have prevented them" (Grady, New York Times, 3/23).
In the meantime, the FDA's action has drawn congressional attention. Rep. Henry Waxman (D-Calif.) has called for a congressional investigation to determine why the FDA decided to allow Rezulin to remain on the market "in the hope that monthly blood tests would protect patients from liver failure." At the same time, House Commerce Committee Chair Thomas Bliley (R-Va.) cautioned the FDA in investigating Dr. Robert Misbin, the agency medical officer who began pushing for Rezulin's withdrawal in January (Los Angeles Times, 3/23). Sidney Wolfe of Public Citizen lobbed criticism at the FDA through HHS Secretary Donna Shalala, asking her to enforce the 1958 Code of Ethics for Government Service. According to the code, those in government should "put loyalty to the highest moral principles and to country above loyalty to persons, party or Government department." Wolfe asked Shalala to punish FDA personnel that were "responsible for interfering with the duty of other employees to voice their concerns about serious problems with drug safety or other similar matters." He said, "The only way to restore the ability of the people to do the job they want to do is to stop telling them to shut up, or summoning them to the internal affairs committee when they disclose some problem." But FDA spokesperson Brad Stone said, "We don't believe that environment exists at FDA" (Manning, USA Today, 3/23).