This week, Dr. Margaret A. Hamburg, Commissioner of the Food and Drug Administration (FDA), sent a letter to colleagues and staff regarding the disclosure of financial conflicts of interest (COIs). The purpose of her letter was to share her perspective on “the challenge of assembling top experts to advise the agency while maintaining the integrity of FDA’s decision making processes. It also served as a message to make staff aware of “a new draft guidance on transparency and advisory committees,” which she hopes will address these challenges.
FDA Advisory Committees
FDA is advised by 49 committees with more than 600 members. These committees provide advice on specific regulatory decisions, such as product approvals, and general policy matters, such as regulations and guidance. As a result, these committees are critical to public health and patients because they provide independent, expert advice on significant scientific, technical, and policy matters that assist FDA’s mission of protecting and promoting the public health. They are also important because they bring high-quality input to FDA in order to support agency decisions
In asking agency officials about the challenges of assembling expert panels, Dr. Hamburg noted that “a common theme was that for highly technical topics, review centers were having difficulty finding experts with the appropriate training and background to provide the agency with informed advice.”
The reality is there is no difficulty finding experts, rather, it is that “some meetings require expertise that is limited to a handful of experts,” the majority of which put their expertise into collaboration with industry. Dr. Hamburg expressed that these people “can often have conflicts of interest.”
JAMA Article
Despite this belief, a study conducted in 2006 in the Journal of the American Medical Association (JAMA) examined this issue and published an article titled, “Financial Conflict of Interest Disclosure and Voting Patterns at Food and Drug Administration Advisory Committee Meetings.”
The study examined a total of 221 meetings held by 16 advisory committees. Of the committees studied, 7 of 16 were able to keep their conflict rates at or below 20%. The research also found that only 28% of advisory committee members and voting consultants combined disclosed a conflict. Overall, the study 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.
From these findings, the researchers concluded that a weak relationship between certain types of conflicts and voting behaviors was detected, and that excluding advisory committee members and voting consultants with conflicts would not have altered the overall vote outcome at any meeting studied.
Dr. Hamburg
In putting together advisory committees, FDA can grant waivers for experts, but may not exceed a cap set in the law on the number of waivers to be granted. For fiscal year 2010, this cap is set at about 13% of all advisory committee members participating in advisory committee meetings. Interestingly, some believe that this draft guidance was issued because 218 positions of the 600-plus on FDA's 49 advisory committees have yet to be filled. Dr. Hamburg confirmed this by noting that currently, the FDA is “granting waivers for less than 5%.”
She noted that conflict-of-interest waivers for scientific advisers have been “controversial” because “the agency’s decision making can be undermined if … FDA isperceived to rely heavily on conflicted experts.” With one third of their positions vacant, the FDA is being perceived as understaffed, and under resourced, which is causing delays in drug and device approvals which hurts patients. So then, what undermines FDA more, hiring experts for panels who disclose their financial interests that have no impact on votes, or delaying treatment and patients to Americans?
But the FDA commissioner would rather have empty positions than the best experts in the world because she feels “it is clearly better for the agency in fulfilling its public health mission when advisors have no conflicts of interest.”
It is disappointing that Dr. Hamburg should make the decision of preventing experts to serve on panels that bring drugs and treatments to sick patients.
I’m sure if we asked the thousands of patients waiting for cancer treatments their opinion about experts on these committees we would get a much different statement.
Accordingly, it should come as no surprise that FDA staff “search far and wide for experts who have the requisite knowledge without conflicts of interest” because the fact is, the most highly trained and experienced experts and clinical investigators work with industry.
Dr. Hamburg notes that “many of the top authorities in specific areas may have conflicts of interest,” and admits that “to make the best decisions, FDA must, at times, seek advice from these experts.” In choosing these experts, Dr. Hamburg asked her staff to take three steps which are consistent with existing FDA policy:
1. Consider the nature of the conflict of interest, recognizing that not all conflicts are created equal.
2. Consider the type of advice to be provided by the advisory committee. A waiver may be more appropriate for general products than for a meeting focusing on approval of a specific product.
3. Justify waiver recommendations with a description of the search for equally expert advisors without conflicts and an explanation of why the individual’s participation is needed to afford the advisory committee essential expertise.
Guidance Draft – April 2010
The guidance applies to Special Government Employees (SGEs) and regular Government employees invited to participate in FDA advisory committees subject to the Federal Advisory Committee Act (FACA). The types of advisory committee meetings within the scope of this guidance are meetings involving particular matters as defined in regulations issued by the Office of Government Ethics (OGE).
The guidance proposes that the agency expand the information disclosed about waivers, so that the name of the company or institution associated with the financial interest would also be posted to the internet prior to committee meetings.
To facilitate such disclosure, FDA plans to prepare a document listing the financial interests for which a waiver is sought, which will basically be a template for individuals to submit. Using the template format, FDA will list personal and immediate family interests separately from other imputed interests. Imputed financial interests are those that are attributed to the individual through his employer (i.e., the employer has a relevant financial interest) or through his position as an officer, director, trustee, or partner. Even though the individual may not have any personal involvement in these interests, they are considered conflicts of interest under the applicable law. The template, which FDA will post on their website whenever a waiver of conflict of interest is granted, will:
1) Identify the type of interest;
2) Identify the nature of the interest (name of company); and
3) The magnitude of an interest by a dollar range, such as $0-5000.
FDA would not disclose the name of a company or institution if doing so would reveal that company’s confidential commercial information. There would also be a template for the waivers would also posted on FDA website along with the disclosure documents at least 15 days prior to the relevant advisory committee meeting. For conflicts of interest that FDA becomes aware of less than 30 days prior to the meeting and for which a waiver is issued, FDA will post the documents as soon as possible and no later than the day of the meeting.
Additionally, FDA plans to post on the same website a roster of all advisory committee members expected to attend a specific meeting at the same time briefing materials for that meeting are posted.
It was also noted throughout the entire guidance document, that these are only suggestions and recommendations, and do not establish legally enforceable responsibilities unless specific regulatory or statutory requirements are cited.
The templates for FDA’s waiver and disclosure form are at the bottom of the guidance document.
Discussion
As one former FDA senior official, charged with advisory committee oversight noted, those who receive waivers do so because “FDA professional career staff made a strong case that these people weren’t just important to the advisory committee — but critical.” The fact that over a third of positions on these committees are vacant is proof that “the conflict-of-interest policy has made it more difficult to properly recruit for advisory committees,” as the Pink Sheet noted.
This kind of absence is harmful to patients, industry and physicians because as John Jenkins, director of the Office of New Drugs, noted at the FDA/CMS Summit in December 2009, "there have been places where FDA felt they didn't have the right experts and they cancelled the meetings." Citing this example, he told attendees the “FDA may have gone too far."
Conclusion
As the guidance itself states, “the advisory committee system enhances FDA’s ability to protect and promote the public health and maintain the public trust by enabling the agency to obtain the benefit of independent, professional expertise.” Since FDA already implements a rigorous process for soliciting and vetting candidates for advisory committee meetings to minimize any potential for financial conflicts of interest, this new guidance may cause even greater problems.
For almost a decade, FDA has reviewed Confidential Financial Disclosure Reports, in advance of each upcoming meeting, once the meeting topics have been identified, to determine whether any financial conflicts of interest may exist for these individuals. Moreover, FDA screens advisory committee members broadly for covered relationships that could present even the appearance that they have conflicts of interest that could affect their impartiality.
The concern of the agency should not be about “conflict of interest” since there are so many ways the agency already accounts for them. The focus should be about “interest,” and as Dr. Pitts and we have said numerous times, “having an “interest” is not necessarily a bad thing – as long as you’re transparent about it.”
In the end, what we are facing is the possibility that FDA will soon allow advisory committees to become “the realm of the second best and the almost brightest.” If that becomes the case, Dr. Pitts notes, then FDA will have done a significant disservice to the advancement of America’s health.
America has always shared a strong tradition of having the best people in the best places, at the best time, to make the best decisions. It is no coincidence that these people often have a multitude or commonality of interests because it is that very diversity of experience that gives them the skills to solve complex problems. As is evident, FDA and Congress have already pushed away a third of these people from committees that want to genuinely want to help people and bring research and medicine to patients without delay. With 31 million more people soon to need these treatments, can we really afford to have more vacancies for much longer?
Send In Your Comments
Comments and suggestions regarding this draft document should be submitted within 60 days (until June 17, 2010). We encourage you to send your comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
For questions on the content of this guidance, contact Michael Ortwerth, Office of Special Medical Programs at 301-796-8220.
Key Documents: