A House committee is seeking to prohibit FDA members who have a financial interest in a company proposing a new drug (or in its competitors) from voting on new drug approvals from that company.
A House committee is moving to prohibit members of FDA advisory committees from voting on whether new drugs should be approved when the members have any financial interests in a company proposing a new drug, or in its competitors. That tightening of federal law would have prevented 2 psychiatrists from voting at the last meeting of the Psychopharmacologic Drugs Advisory Committee (PDAC), which took place on March 23 to consider an application by Cephalon Inc to get a label for attention-deficit/hyperactivity disorder (ADHD) for modafinil (Provigil).
Wayne Goodman, MD, chair of the PDAC as well as chair of the department of psychiatry, University of Florida, and Andrew Leon, MD, professor of biostatistics in psychiatry at Cornell Medical School, were granted waivers at that meeting and allowed to vote. Seven permanent members of the committee and 5 temporary members were present. Other members of the PDAC had been granted waivers at previous committee meetings.
Before each PDAC meeting, the FDA staff decides which members qualify for waivers. Generally, waivers are granted when a member's financial interest is not so substantial as to be deemed likely to affect the integrity of the services that the Government may expect. The size of the financial interest is a key factor under this standard. But federal law also allows a waiver when the FDA staff determines that the need for the individual's services outweighs the potential for a conflict of interest.
The House Appropriations Committee approved a bill in May that sets out funding for the FDA in fiscal year 2007, starting October 1, 2006. That bill included an amendment, sponsored by Rep Maurice Hinchey (D-NY) that would prevent the FDA from granting waivers to advisory committee members prior to a committee meeting.
The March 23 meeting of the PDAC focused on Cephalon's application to get a label for ADHD for modafinil, which is currently marketed to improve wakefulness in adults with excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome, and shift work sleep disorder. Cephalon plans to rename the ADHD version Sparlon and wants to label it for children and adolescents. The FDA staff had been concerned about the drug's link to rashes, and the PDAC declined on March 23 to recommend FDA approval, mostly for that reason.
PDAC advisors are asked to evaluate the safety and efficacy of investigational agents, stated Leon in an interview. We are expected to be objective. For that reason, transparency in revealing potential conflicts is critical. Unless our financial or intellectual conflicts are too great, full disclosure serves that purpose.
Goodman's term ends in June. At the time when this story was written, he had not yet been asked to return. During his 2-year tenure as chairman (he served 1 year previously as a regular committee member), he cast a controversial vote in favor of a black-box warning on antidepressants, which has made him something of a bte noir among colleagues and psychiatric groups. At the March 23 meeting, Thomas Laughren, MD, director, division of psychiatry products, said, Now, Wayne told me after the September 2004 meeting on antidepressants and suicidality in pediatric patients that he didn't have any friends any more in the academic and clinical community. I just want to assure him that he always has friends here at FDA.
Crystal Rice, an FDA spokeswoman, said she could not comment on why Goodman had not been asked to continue on the PDAC. We would not discuss with an outside party why or why not we would ask someone to continue as an advisory committee member, she responded in an e-mail. Such a discussion should be between the two parties involved.
In an interview, Goodman said colleagues and drug company executives censured him privately for his vote in favor of a black-box warning because they felt the warning would discourage young people and their families from seeking treatment for depression. Goodman's vote helps underline some of the muddy assumptions about conflict-of-interest rules. Goodman owns no stock in any drug company, nor does he serve as a principal investigator. His only conflict is the fact that colleagues at the McKnight Brain Institute at the University of Florida do have contracts with companies working on psychiatric drugs.
So, even though Goodman nominally had a conflict, he nonetheless voted against the interests of the drug industry. Goodman expressed the belief that, in his judgment, all members of the advisory committee cast their votes based on what is best for the public welfare based on the data at hand.
Had the amendment adopted by the House Appropriations Committee been in force for the past few years, Goodman would not have been allowed to vote at either the March 23, 2006, or the September 2004 meeting, and probably others in between. Hinchey offered the same amendment last year--outlawing conflict of interest waivers--and it was passed by the House. However, the Senate approved a much weaker conflict-of-interest amendment that eventually prevailed when House and Senate leaders came together to reconcile differences in the 2 versions of the bill.
But Hinchey may have more success convincing the Senate this year. The April issue of the Journal of the American Medical Association included an article detailing the conflicts of interest declared by members of FDA advisory committees. The authors of this study, Peter Lurie, MD, MPH, of Public Citizen's Health Research Group, Washington, DC, and colleagues, collected data from January 1, 2001, to December 31, 2004, by analyzing agendas and transcripts from all FDA Drug Advisory Committee meetings listed on the FDA Web site. A total of 221 meetings held by 16 advisory committees were included in the study. In 73% of the meetings, at least one advisory committee member or voting consultant disclosed a conflict; only 1% of advisory committee members were recused, the authors found.
Goodman believes that members of an advisory committee who hold stock in or serve as a principal or co-principal investigator for a sponsor of clinical trials or a company with a rival product should not be able to vote at an advisory committee meeting. Nor should any member be receiving honoraria from drug companies or have stock in those companies--although he argues for granularity in the latter category--while sitting on the advisory committee.