Over the past year, Congress has been extremely busy putting together User Fee Act legislation that will reauthorize the Prescription Drug User Fee Act (PDUFA) and the Medical Device User Fee Act (MDUFA). Throughout negotiations, several pieces of legislation were proposed regarding conflict of interest waivers and Advisory Committees at the Food and Drug Administration (FDA). There has been concern from various stakeholders about vacancies on such committees and the effect this may have on slowing drug approval.
Consequently, the reconciled User Fee Act legislation—known as the Food and Drug Administration Safety and Innovation Act (FDASIA)—includes a provision that would loosen the requirement for the number of waivers FDA could grant to individuals who could serve on FDA Advisory panels. The bill already passed the House and awaits a final vote by the Senate.
As reported by Pharmalot, the FDA is currently permitted to issue a set number of waivers to individuals who the agency would like to serve on a panel, but have a conflict. The number of waivers depends on how many meetings and members participate in a given year. The cap is on the actual percent of members granted waivers. For fiscal year 2012, the cap is 11.5 percent, according to the FDA. Under the new provision, FDA officials will be allowed to grant as many waivers as they want.
This amendment should be passed because it will ensure that patients get lifesaving medicines in a timely manner. Moreover, concerns that such a provision will lead to conflicts of interest or bias are misplaced. In fact, evidence from a 2006 article in the Journal of the American Medical Association (JAMA) reported that the meeting-level analysis did not show a statistically significant relationship between conflict rates (“index conflict,” “competitor conflict,” or “any conflict”) and voting patterns.
In other words, the researchers tested for a relationship not between conflict of interest and yes votes on a drug but between conflicts of interest and votes for the interest of a pharmaceutical company. Moreover, the research indicated that in all 3 conflict categories, the exclusion of advisory committee members and voting consultants with conflicts would have produced margins less favorable to the index drug in the majority of meetings, but this would not have changed whether the majority favored or opposed the drug.
To verify this, FDA contracted with Eastern Research Group, Inc. (ERG) in both 2007 and 2009 to assess the relationship between expertise and financial conflicts of interest of FDA advisory committee members. ERG continued the Lurie JAMA study cited above and extended it beyond December 2004 through the first quarter of 2008 (analyzing advisory committee meetings). The 2007 report had several important findings that support the recent FDASIA’s amendment to remove strict conflict of interest requirements for Advisory Committees.
ERG conducted four meeting-level and two individual level analyses to assess the relationship between financial interests and voting patterns. ERG found that the expanded dataset produced meeting-level results similar to Lurie’s findings. Specifically, ERG found no statistically significant relationship between conflict rates and voting outcomes (α=0.05) when considering financial ties with: the product sponsor (“index conflict”), a competitor of the sponsor (“competitor conflict”), or the product sponsor or a competitor or both (“any conflict”). ERG also found individual-level results similar in direction to Lurie’s findings. Overall, ERG found no evidence to suggest that having a financial conflict-of-interest tends to increase votes in favor of that interest
In addition, the report found that it would be difficult to find alternative experts because they would also require waivers and creating “conflict-free advisory panels” would create a “substantial additional burden on the cost and timeliness of advisory committee operations.” The report also found that FDA might “not always be able to match the specialized expertise of some existing advisory committees.” Ultimately, FDA suggests that Lurie’s results provide “further evidence against the charge that the financial interests of voters taint committee votes”
Background
Advisory committees play an important role in FDA’s mandate to promote and protect the public health by allowing the agency to engage independent, technical experts from a variety of disciplines. The committees are often comprised primarily of individuals working in academia; but also may have representation from private practices, professional and patient groups, regulated industry, and other government agencies.
In circumstances where FDA staff seeks additional input because of such things as emerging research, the complexity of a new technology, or conflicting scientific data, FDA may turn to outside experts to provide important insights that would help inform our decision-making. FDA often asks “these experts to advise them on a range of scientific questions – including whether the safety of a drug is properly characterized for patients or if a new device would provide meaningful benefit for patients.”
While “FDA ultimately makes the final decision on all regulatory activities,” advisory committee experts, “which include patients, provide invaluable insights to the agency on how the broader public will approach a particular product or issue.”
Before each meeting, FDA screens all advisory committee members who are special government employees or regular government employees for potential financial conflicts of interest. FDA asks the members to report to the agency any past and all current involvement or relationships with the products, companies, and issues related to the meeting. Members are required to report all current financial interests that could be affected by the outcome of the advisory committee proceedings and any FDA decision based on the committee’s recommendations. For example, this might include stocks and investments and consulting arrangements. In addition, they report involvements that might present an appearance of a conflict, to the best of their knowledge.
Conflicts of Interest
Section 1142 of FDASIA would amend Section 712 of the Federal Food, Drug and Cosmetic Act (FFDCA) by requiring the Secretary of Health and Human Services to
- develop and implement strategies on effective outreach to potential members of advisory committees at universities, colleges, other academic research centers, professional and medical societies, and patient and consumer groups;
- seek input from professional medical and scientific societies to determine the most effective informational and recruitment activities;
- at least every 180 days, request referrals for potential members of advisory committees from a variety of stakeholders, including—
- product developers, patient groups, and disease advocacy organizations; and
- relevant (I) professional societies;II) medical societies; III) academic organizations; and (IV) governmental organizations; and
- take into account the levels of activity (including the numbers of annual meetings) and the numbers of vacancies of the advisory committees.
The recruitment activities may include—A) advertising the process for becoming an advisory committee member at medical and scientific society conferences; (B) making widely available, including by using existing electronic communications channels, the contact information for the FDA point of contact regarding advisory committee nominations; and (C) developing a method through which an entity receiving funding from the National Institutes of Health, the Agency for Healthcare Research and Quality, the Centers for Disease Control and Prevention, or the Veterans Health Administration can identify a person whom FDA can contact regarding the nomination of individuals to serve on advisory committees.
As soon as practicable, but not later than 15 days prior to a meeting of an advisory committee, the Secretary must disclose on FDA’s website (A) the type, nature, and magnitude of the financial interests of the advisory committee member to which such determination or certification applies; and (B) the reasons of the Secretary for such determination or certification, including, as appropriate, the public health interest in having the expertise of the member with respect to the particular matter before the advisory committee.
In the case of a financial interest that becomes known to the Secretary less than 30 days prior to a meeting of an advisory committee, the Secretary must disclose on FDA’s website, the information described in subparagraphs (A) and (B) of paragraph (1) as soon as practicable after the Secretary makes such determination or certification, but in no case later than the date of such meeting.
Not later than February 1st of each year, the Secretary must submit to the Committee on Appropriations and the Committee on Health, Education, Labor, and Pensions (HELP) of the Senate, and the Committee on Appropriations and the Committee on Energy and Commerce of the House of Representatives, a report that describes—with respect to the fiscal year that ended on September 30 of the previous year,
- the number of persons nominated for participation at meetings for each advisory committee,
- the number of persons so nominated, and willing to serve,
- the number of vacancies on each advisory committee, and
- the number of persons contacted for service as members on each advisory committee meeting for each advisory committee who did not participate because of the potential for such participation to constitute a disqualifying financial interest.
Second, the report must describe the number of persons contacted for services as members for each advisory committee meeting for each advisory committee who did not participate because of reasons other than the potential for such participation to constitute a disqualifying financial interest. Third, the report must describe the number of members attending meetings for each advisory committee. Finally, the report must describe the aggregate number of disclosures and the percentage of individuals to whom such disclosures did not apply who served on such committee. Not later than 30 days after submitting any report, the Secretary must make the available to the public.
The Secretary must also review guidance of FDA with respect to advisory committees regarding disclosure of conflicts of interest and update such guidance as necessary to ensure that FDA receives appropriate access to needed scientific expertise. The Secretary must issue guidance that describes how the Secretary reviews the financial interests and involvement of advisory committee members that are disclosed but that the Secretary determines not to meet the definition of a disqualifying interest under.
Ultimately, this amendment is common sense and will likely be included in the final bill. There is no reason why patients should have to wait longer for their medicines or companies face delays in approval because FDA is having trouble filling seats on panels. This is especially true considering a JAMA study several years ago revealed that FDA advisory committees.
The number of qualified individuals and experts who work with industry will always be high, and as a result, it will always be difficult for FDA to fill these spots. Accordingly, this legislation will ensure that committees are full and that the proper firewalls are in place to protect the balance of such committees to ensure patients get lifesaving medicines as fast as possible. If the legislation is passed, it will certainly be interesting to see whether there is an increase in approval time for certain drugs, but as the 2006 JAMA study demonstrated, increased conflicts are unlikely.