FDA Issues New Conflict of Interest Guidelines

by Sam Kim, 4/3/2007

The U.S. Food and Drug Administration (FDA) issued a proposal that revised its criteria for determining whether scientific advisory committee members have financial conflicts of interest. The guidance, which would be nonbinding if adopted, is in its draft form and will be open for comment upon publication in the Federal Register. The guidance simplifies FDA's process for determining financial conflicts of interest. It also details exceptions agency personnel can make to allow scientists with conflicts of interest to serve on panels. The proposal comes as FDA faces increasing scrutiny over its ties to the pharmaceutical industry.

FDA advisory committees are standing panels comprised of individuals considered experts in a particular field. Members are generally non-governmental employees but may also include government employees outside of the office to which the panel is making recommendations. Committees are comprised primarily of members with scientific interests, but may also include members representing consumer, industry and patient interests. Advisory committees vote to provide nonbinding recommendations to FDA.

Federal law requires agencies to screen advisory committees for financial conflicts of interest. The guidance points out, because FDA advisory committees are integral in the agency's regulatory decision making, "the public has a particular interest in and high expectations for FDA's process." FDA recently identified assessment of potential conflicts of interest as an area in need of improvement.

On March 21, FDA released a proposal which would "streamline" the agencies process for assessing financial conflicts of interest. The guidance includes detailed instructions agency personnel should use when considering advisory committee members. Agency personnel should determine whether the candidate has a disqualifying financial interest. The proposal defines a financial interest as "the potential for gain or loss to the employee as a result of governmental action on the particular matter." A member's family, partners, employer, prospective employers, and organizational ties should be considered.

The guidance sets a threshold of $50,000 for determining the severity of a conflict of interest. The guidance suggests potential members with a financial interest of more than $50,000 should not serve on panels. Those with a financial interest less than $50,000 may participate but only as non-voting members.

The guidance also instructs personnel to consider financial interests the candidate may have had in the preceding year, regardless of whether those interests still apply. This provision exceeds statutory criteria for determining conflicts of interest.

However, the proposal also includes criteria for granting exemptions to potential committee members with financial conflicts of interest. This is in accordance with federal statute, which requires certain provisions for exemption.

One of these exemptions applies to non-governmental employees. Upon determining an individual has a financial interest greater than $50,000, the guidance instructs agency personnel to ask: "Does the need for the individual's services outweigh the potential for a conflict of interest?" If the answer is "yes," the member could serve on the panel but could not vote.

The guidance suggests ways to determine whether the need for an individual supersedes financial interest. One factor is the determination of the uniqueness of the individual's expertise. The guidance states, "Need will be most persuasively shown when a reasonably thorough search for a similarly or better qualified candidate with fewer conflicts can be documented."

Other suggestions for determining need involve qualifying in some way the conflicts that led to the determination of financial interest. For example, personnel are to consider "the extent to which the disqualifying financial interest could be affected by the actions of the advisory committee." The guidance does not indicate who in the agency should make these determinations.

OMB Watch is concerned about the factors the guidance identifies in determining the "need for the individual's services." In comments the organization plans to submit, OMB Watch states, "Allowing agency personnel to qualify conflicts undermines the original criteria for determining financial interests. Conflicts either exist or they do not. Mitigating the severity of a conflict of interest should not be an option." OMB Watch also critiques the proposal for setting a seemingly arbitrary level of $50,000 for exclusion from committees, and encourages FDA to include its rationale in the final guidance.

"Currently, the proposal includes several loopholes which could allow agency personnel to advance a political agenda and sacrifice scientific integrity in the process," OMB Watch says in its comments. "If FDA closes these loopholes, this conflict of interest guidance will provide a fine framework for agency personnel and set a course for other agencies to follow."

FDA's decision to address ties between advisory committee members and industry comes in the wake of two House hearings which addressed the agency's drug approval process. At the second hearing on March 22, FDA Commissioner Andrew von Eschenbach defended the agency in front of the House Energy and Commerce subcommittee on Oversight and Investigations. Commenting on high-profile drug safety failures such as the Vioxx incident, subcommittee Chairman Bart Stupak (D-MI) said, "FDA officials responsible for protecting Americans overruled their own scientists and chose instead to listen to the self-interested pleadings of the drug companies."

The hearing revisited the 2006 controversy over the antibiotic Ketek, which was rushed to market despite warnings from agency scientists about the drug's potential side effects. Von Eschenbach claimed FDA did not rely on false safety studies despite contrary claims posted on the agency's website. On March 28, Stupak and Committee Chairman John Dingell (D-MI) sent a strongly worded letter to Michael O. Leavitt, the Secretary of Health and Human Services. The letter announced the lawmakers intent to investigate possible efforts by Von Eschenbach to "intentionally mislead the Subcommittee" and requesed documents to that effect.

Lawmakers are likely to continue to examine industry's influence at FDA as Congress prepares to reauthorize the Prescription Drug User Fee Act (PDUFA). PDUFA authorizes FDA to collect fees from pharmaceutical companies which are then used to conduct safety studies on specific drugs. The fees are tied to "performance goals" that prompt FDA to expedite the approval process. PDUFA is set to expire on Sept. 30, the end of the fiscal year.