‘High Dollar’ Conflicts Should Nullify FDA Advisory Panelists – Public Citizen

FDA advisory committee members with large financial conflicts of interest should be recused from meetings in which these conflicts may come into play, Public Citizen recommends after conducting a study on voting patterns.

However, the authors found only a "weak relationship" linking some types of conflicts with voting patterns, and determined that exclusion of such members would not affect voting outcomes.

Public Citizen's Health Research Group, led by Peter Lurie, MD, analyzed transcripts and agendas from 221 meetings held by 16 advisory committees between 2001 and 2004 to identify potential links between conflicts and voting behavior.

The findings and recommendations appeared in the Journal of the American Medical Association April 25.

Currently, conflict of interest disclosures are regulated under a draft guidance issued by FDA in January 2002 (¹ 'The Tan Sheet' Feb. 4, 2002, In Brief).

"Although the draft guidance has produced an improvement in some respects, there is room for more public disclosure beyond the guidance's requirements," Lurie et al. suggest.

"FDA should ensure total compliance with the current draft guidance, particularly for the conflict details (conflict value, competitor status) that we found undisclosed in about 5% of conflicts covered by the draft guidance," the group recommends.

The agency also should extend the guidance to cover all meetings, and not just those that deal with specific products, the authors say.

Public Citizen previously took this position in 2002 comments to the agency (² (Also see "Conflict of Interest Waiver Details For Cmte. Members Should Be Public – BMS" - Pink Sheet, 8 Apr, 2002.), p. 17).

However, the study only drew data from "product meetings" and not those that discussed more general scientific issues ("nonproduct meetings"). Nonproduct meetings "typically do not consider questions that can be readily analyzed," Lurie explains.

FDA should also be required to identify competitor companies and explain the reasons behind a member's recusal, if such action is taken, the report says.

Finally, guest speakers invited by the agency should be required to make disclosures similar to those expected of advisory committee members and voting consultants.

"Ideally, all panels of scientific experts advising a federal decision-making body would be free of financial conflicts of interest with the affected companies," Lurie et al. maintain.

For advisory committee members with smaller conflicts of interest, the group asserts that "full transparency, including disclosure several days before the meeting, is necessary to allow the objective evaluation of committee decisions."

While the researchers did not identify a great impact on voting results related to conflicts, they determined that "disclosures of conflicts of interest at drug advisory committee meetings are common, often of considerable monetary value, and rarely result in recusal of advisory committee members."

"A weak relationship between certain types of conflicts and voting behaviors was detected, but excluding advisory committee members and voting consultants with conflicts would not have altered the overall vote outcome at any meeting studied."

In one analysis, the authors discovered a "paradox of competitor conflicts being associated with voting for the index drug," as members with this type of conflict were 20% more likely to vote in favor of the index drug than against.

However, exclusion of such members would not have changed the overall vote, they note.

These positive findings "support our conclusion that a weak association between certain conflicts and voting behavior exists."

Analyses of "index conflict," or associations with the sponsor company were "particularly underpowered," which may have accounted for the lack of a signal among index conflicts while competitor conflicts showed a significant relationship, Lurie et al. say.

Furthermore, the screening process used by FDA might have produced "a relatively lower level of conflict among those with index conflicts as compared to competitor conflicts."

Such a conflict also "might be a proxy for an attitude relatively favorable to industry."

The majority of meetings (73%) involved at least one committee member or voting consultant who disclosed a conflict, Lurie et al. discovered. However, only 1% of these members were recused.

The most common conflicts involved consulting agreements, investments and contracts/grants, researchers found; 34% of advisory committee members and 51% of voting consultants disclosed a consulting agreement, and 30% of committee members and 19% of voting consultants disclosed investment information.

Such agreements are of "considerable monetary value," the research group notes, as 19% of consulting arrangements involved over $10,000, 23% of contacts/grants exceeded $100,000, and 30% of investments surpassed $25,000.

These dollar amounts for their corresponding types of conflict are too high for members to be allowed to remain on the panel, Lurie says.

"Advisory committee members with such large conflicts of interest should be recused from the meetings in which these conflicts exist, and alternative voting consultants should be found if they have conflicts of interest of similar magnitude."

"Certainly, advisory committee members who have conflicts of interest with higher dollar values should not be allowed to participate," the authors maintain.

A significant proportion of conflicts - 22% of advisory committee conflicts and 20% of voting consultant conflicts - linked members to the sponsor company, Lurie et al. note.

Conflicts also affect the public comment portions of meetings, the authors say, citing 47 instances in which public speakers were flown in by sponsors, "including one meeting in which four people were flown in."

"This demonstrates that sponsors are using the public session to influence the advisory committee meetings' outcome and may create an unbalanced representation of the public's viewpoint," they state.

In July 2005, Public Citizen submitted comments asking FDA to allow committee members and voting consultants to question speakers on their financial interests (³ (Also see "Open Public Hearing Speakers Should Disclose Financial Conflict – Comments" - Pink Sheet, 18 Jul, 2005.), p. 9).

In "at least 32 instances, groups appearing to represent patients received funding from a company potentially affected by the day's deliberation," the report says.

"This finding amplifies the growing concern that pharmaceutical industry sponsorship is becoming more prominent in nonprofit, patient advocacy groups that were once viewed as grassroots organizations independent of industry influence."

Conflicts of interest could impact voting patterns on the meeting level and the individual level, the authors note; overall conflict could influence voting behavior at the meeting level. On the individual level, "particular voters would be affected only by their personal conflicts and vote accordingly."

The group acknowledges limitations to their study, including that the analyses were hampered by small sample sizes. Only half of the meetings were product-specific, they note; 76 posed questions amenable to the analysis. Approximately half of those (36) were unanimous, and "many other meetings had no conflict."

"Our results are thus most meaningful in the competitor conflict and any conflict categories," Lurie et al. state.

Researchers looked to the four-year period between Jan. 1, 2001 and Dec. 31, 2004 (approximately one year before and three years after the guidance was issued) to collect their data.

Meetings covering a single product were treated as one meeting, while meetings covering multiple products were divided, with each individual product being treated as one meeting for purposes of analysis, Lurie et al. explain.

The group included data on advisory committee members, voting consultants, and public hearing participants who were listed in the transcripts; other government employees, industry employees, guest speakers and nonvoting industry panelists were excluded.

- Melina Vissat