The Food and Drug Administration took the unusual step of removing a member of one of its influential advisory committees after the maker of a drug under consideration complained about a potential conflict of interest.
Thomas Fleming, a prominent statistician at the University of Washington, said the FDA late last week rescinded his invitation to serve on a committee that yesterday reviewed a new use for Factive, an antibiotic made by Oscient Pharmaceuticals Corp. In a Sept. 1 letter, Oscient complained to the FDA that, among other things, Dr. Fleming was biased against a type of trial design the company used.
The panel voted 11-2 against FDA approval of Factive's use to treat sinusitis. The FDA, which expressed skepticism about that use of the drug, tends to follow its committees' advice.
Dr. Fleming, a longtime FDA committee member who has served in dozens of meetings, said the agency waived two potential conflicts that he initially disclosed.
But last week, according to Dr. Fleming, the agency asked him to review his records for any other possible conflicts. He found that in late 2002 and early 2003, he had been paid $6,000 to review completed studies of Factive for a predecessor company of Oscient, though not about its use in sinusitis, he said. He had also consulted on another drug for a different Oscient predecessor. He said he earlier hadn't recalled the past relationships, and the FDA had originally asked about ties to Oscient, not specifically mentioning the names of predecessor companies.
Late last week, the FDA told Dr. Fleming that because the agency didn't have time to weigh whether the newly disclosed issue deserved a waiver, it couldn't allow him to serve on the committee.
Dr. Fleming said the agency didn't tell him that before its most recent inquiry about conflicts, it had received a letter from Oscient. Dr. Fleming said the letter raised concerns about his past consultation with Oscient's predecessor companies and said he might have a conflict of interest because he has publicly questioned the type of study used to prove Factive's efficacy, known as a "noninferiority trial."
In a noninferiority trial, used in FDA approvals of antibiotics, a new drug's efficacy has to be shown to be roughly equal to an old drug. Critics argue that it isn't always clear how much better the old antibiotics are than placebo pills. So if a new drug is approved because its results are slightly, but not significantly, worse than those of an old drug, there is a risk that it hasn't actually done better than a sugar pill.
Defenders of noninferiority designs say that patients with infections, even less-serious ones such as sinusitis, can't ethically be asked to take placebos in a study. Congress is scrutinizing the FDA's use of such trials, but the agency is also under pressure to grant fewer conflict waivers to committees.
The FDA said that after recently being informed about Dr. Fleming's potential conflicts, it didn't have time to "resolve the issue before the start of the meeting," so the agency decided "in order to protect the integrity of the process, the most prudent decision was to have the individual refrain from participation in today's meeting." The decision wasn't connected to Dr. Fleming's views on any particular trial design, the agency said.
A spokeswoman for Oscient said it "intends for all of our communications with the FDA to remain confidential" and declined to comment about its interactions with the agency.
Dr. Fleming said that he believes the FDA has granted waivers for conflicts of similar or greater magnitude, and he has in the past supported approval of some drugs tested in noninferiority trials. "This opens the door for a sponsor to make an allegation so late that even if it isn't substantive, the person is disqualified," he said, adding that there are "substantive concerns that the integrity of the advisory committee process . . . would be significantly compromised if there is a possibility that a company could intervene in the committee-making process."
Drug Pipeline
No comments:
Post a Comment