FDA Investigating Rezulin Clinical Trials
The Food and Drug Administration has opened an investigation into whether the manufacturer of the diabetes pill Rezulin improperly reported findings of liver injury among patients in early clinical research.
The investigation, according to people familiar with the matter, comes as FDA Commissioner Jane E. Henney plans to meet about Rezulin today with a handful of senior aides, including Dr. Murray M. Lumpkin, the deputy drug-center director. Over the last two months, Lumpkin has resisted agency physicians who favor withdrawal of the drug.
The FDA has linked 89 voluntarily reported cases of liver failure--including 61 deaths--to the use of Rezulin.
An FDA spokeswoman, Laura Bradbard, acknowledged Tuesday that officials were examining allegations lodged this month with the agency and with members of Congress by Dr. Janet B. McGill, a St. Louis endocrinologist who had helped lead two earlier clinical studies of Rezulin.
McGill alleged in a March 1 letter to Sen. Edward M. Kennedy (D-Mass.) that the Warner-Lambert Co., which makes Rezulin, “deliberately omitted reports of liver toxicity and misrepresented serious adverse events experienced by patients in their clinical studies.”
In a separate correspondence, McGill said that she had not noticed until recently that a Warner-Lambert summary report encompassing one of her projects reflected, inaccurately, zero liver-function abnormalities.
A spokeswoman for Warner-Lambert, Carol Goodrich, said Tuesday that the company was cooperating with the FDA. A company executive, Mary E. Taylor, termed McGill’s allegations “false” in a letter issued late Tuesday to the FDA.
Addressing McGill’s specific contention that Warner-Lambert had not properly reported two cases of liver injury from a 1994 clinical trial, Taylor cited documents showing that one of the cases was shared as required with the FDA.
However, Taylor left open the possibility that findings of liver injury in the second case were not reported to the FDA.
“These data were never submitted to [Warner-Lambert] in any of the case report forms filed by Dr. McGill in connection with the study,” Taylor alleged.
Asked if Taylor’s statement was an acknowledgment that the second case of liver injury, in which the patient was hospitalized with jaundice, was not reported to the FDA before it approved the drug, Warner-Lambert’s Goodrich said that she could not elaborate. The Times reported last week that this patient, John D. Slater Jr., recovered but said he had to retire from his job as a limousine driver.
In granting Rezulin a six-month “fast-track” approval in 1997, the FDA believed that two patients in clinical trials had suffered jaundice and that, overall, 1.94% of those who took the drug experienced liver injury. Adding Slater would boost the number of cases of jaundice during clinical trials from two to three.
McGill, the St. Louis doctor, was not available to respond to Warner-Lambert’s letter.
The FDA spokeswoman would not discuss the specific investigative steps now underway. Those familiar with the matter said that representatives from both the FDA’s Office of Criminal Investigations and an internal-affairs unit had begun to make inquiries.
Telephone calls have been made, they said, to Dr. Robert I. Misbin, an FDA medical officer to whom McGill wrote and who has himself urged members of Congress to investigate the agency’s handling of Rezulin.
Reached Tuesday night, Misbin said that he had no comment on the matter.
Times researcher Janet Lundblad in Los Angeles contributed to this story.
