From January 2024 to July 2024, the Federation of American Scientists interviewed 30 current and former Advisory Committee (AdComm) members. Based on these discussions, we were able to source potential policy recommendations that may assist with enhancing the FDA’s ability to obtain valuable advice for evidence-based decision-making. The results of these discussions will be presented in case study format detailing the recurring themes that emerged and policy recommendations for improvement.
The FDA relies on its scientific staff and Advisory Committees to provide conclusions from trial and study data, which aid in the process of regulating and approving medical products. Discussions have been centered around how to appropriately leverage the membership of Advisory Committee experts to assist with areas of difficulty surrounding the safety and efficacy of medical products. Nonetheless, the methods by which these systems currently generate the evidence the Government needs can be improved. This case study focuses on five key areas we believe can assist in fully utilizing the capacity in which AdComms serve and improve overall engagement with AdComms membership.
AdComm Membership Problems
Advisory Committees serve as the core for expert engagement in the Food and Drug Administration’s (FDA) decision-making processes and are composed of medical professionals, industry representatives, patient advocates, and scientific experts. Their primary role is to provide the FDA with informed advice and recommendations on issues spanning science, regulatory policy, and the evaluation of products under the FDA’s jurisdiction.
The intricacies of being an effective AdComm member, however, have been somewhat overlooked. Conversations with current and ex-members have highlighted areas for enhancement that would strengthen the function of AdComms and enrich the advice provided. Feedback indicated a lack of transparency in the FDA’s recruitment methods for committee positions, insufficient orientation or training for new members, limited understanding of regulatory procedures among members, and an onerous conflict of interest protocol that served as a deterrent for some members who were asked to return or renew their membership.
Pathways to Improving AdComms Membership
Committee Composition
The composition of Advisory Committees vary depending on the charter that has been set in place. In some cases, committee composition has been set by law. However, where there is flexibility in determining the composition of a committee, consideration should be given to all categories of expertise that should be included and diversity of voices that are selected to participate in these meetings. Committee composition should reflect the diversity of the world and populations of whom their recommendations could potentially affect. For this reason, discussions with current and former Advisory Committee members indicated the need for three additional areas of expertise that should be included on all Committees. Insights discovered that all Committees should include a patient representative who has the knowledge from lived experience and understanding of how treatments affect day-to-day life. This recommendation was further corroborated by a 3D Communications survey conducted with 400+ FDA AdComm members where results indicated that 48% agreed there should be a patient and consumer representative on all Committees. Members also stated that pharmacists should be included because drugs and devices eventually pass through their hands to give to patients. Pharmacologists should serve on the Committee due to their clinical application knowledge of drugs and devices. Finally, a roster of temporary members should be created for varying categories to use when additional expertise is needed on a Committee because of a conflict of interest or when a certain skillset or knowledge base is lacking on the current Committee.
Role of the Advisory Committee Chair
The FDA describes the purpose of an Advisory Committee chair as one who will “preside at committee meetings and ensure that all rules of order and conduct are maintained during each session”. The chair also has the responsibility of ensuring all recommendations and advice from AdComm members are clear and evidence-based. Moreover, the role of the chair should be used to enhance the overall committee experience as well as be of service to the FDA. Despite these requirements, there’s an underutilization of the chair’s role in terms of communication and stakeholder coordination, as evidenced by the chair not being listed as a primary point of contact for the Advisory Committee and a lack of coordination amongst stakeholders.
Chairpersons are usually selected due to their critical domain knowledge, understanding of best practices, ability to identify risks and keep members engaged, and expansive relationships within their industry. Maximizing the chairperson’s role requires discussion on how to utilize their valuable domain knowledge and professional networks. Chairs possess extensive networks that could support the identification of permanent or temporary expert participants for AdComms, aiding the FDA’s mission to recruit top talent for guidance. This would ensure the FDA’s continued success in recruiting the brightest minds in the industry to assist with providing advice. Additionally, chairs should have oversight in identifying relevant issues or products for their respective committees to appraise, which can provide another layer for the FDA to keep abreast of critical public concerns via appropriate committee evaluation.
Training
Training is a significant part of many Federal Government service positions. However, besides ethics and conflict of interest trainings, there is no set training program in place for most new Advisory Committee members. Considering Advisory Committee members come from different professional backgrounds with varying levels of expertise, the FDA should develop an onboarding training program to assist with acclimating all new AdComm members into their roles. Many former and current AdComm members mentioned that no formal training was provided as part of the onboarding process. Some members who were new to the FDA AdComm process or who were not physicians or scientists stated they had no knowledge of statistical analyses, clinical trial design, or how the FDA views the role of the AdComm in the regulatory process.
A foundational training, covering these aspects, would greatly benefit those members such as consumer and patient representatives who may lack this shared base of expertise. An investment in such an onboarding experience would promote stronger rapport among members and guarantee their preparedness in analyzing scientific and technical submissions.
Learning about the FDA Regulatory Process
The Food & Drug Administration (FDA) was established with the purpose of regulating drugs and medical devices to ensure their safety and effectiveness for all citizens in the United States. Many Advisory Committee members join these committees without basic knowledge of the FDA’s regulatory process. During FAS’ discussions with current and former AdComm members, approximately 71% of members stated that basic knowledge of the regulatory process and how the FDA makes their decisions was unknown to them.
Providing AdComm members with an introductory course on the FDA’s regulatory process could enhance their comprehension, potentially allowing them to make more effective contributions and informed clinical decisions (based on their occupation). Although the FDA provides some online resources about its processes, like FAQs and guidelines, an expansion of this material should be considered for inclusion in AdComm orientation activities.
Conflict of Interest (COI) Process
18 U.S.C. 208(a) prohibits Advisory Committee members who are designated as special government employees (SGE) from serving on federal advisory committees or any other Federal Government form of service that will have a “direct or predictable effect” on their financial interests. Similarly, the FDA describes a conflict of interest as an occurrence “when an individual selected to serve on an advisory committee has financial interests that may be impacted by the individual’s work on the advisory committee”. The auditing process for conflicts of interest is designed to confirm that the members of the advisory committee maintain impartiality and ensure the integrity of public health safety. Prior to any committee gathering, the FDA mandates that each participant, classified as either an AdComm member or SGE, complete an FDA 3410 form that reveals all financial connections that could be seen as potential COIs.
However, the process of what happens after the 3410 form has been completed is ambiguous. In 2007, the FDA submitted draft guidance to the federal register for comment entitled, Guidance for the Public, FDA Advisory Committee Members, and FDA Staff on Procedures for Determining Conflict of Interest and Eligibility for Participation in FDA Advisory Committees in an effort to determine if there is an inappropriate COI that should exclude members from participating in a committee meeting. Moreover, the official guidance is not easily accessible. Another draft guidance was developed with a detailed listing of considerations to be given when examining conflict of interests can be found in the FDA’s draft guidance on Procedures for Evaluating Appearance Issues and Granting Authorizations for Participation in FDA Advisory Committees.
Discussions with current and former AdComm members about the COI auditing process sparked varying views regarding whether flexibility should be exercised for COIs. 82% of members concurred that while they recognize the necessity for such a system, it tends to be overly demanding due to repetitive paperwork, especially when their circumstances remain unchanged. The strenuous nature of this routine has even deterred some from continuing their membership each year and remains a key aspect as to why members choose to end their service.
Despite having a COI process in place, there are loopholes that allow members with conflicts of interest to remain as voting members for specific AdComm meetings. A certain incident involved an Advisory Committee where 10 members who had financial ties to the sponsor were allowed to participate in an AdComm meeting. These individuals ultimately took part in endorsing the TriClip G4 System by Abbott and unanimously agreed that its benefits outweighed the potential risks. To further complicate matters, this information was not disclosed to the public at the time of approval.
While the COI process has resulted in members being rightfully disqualified from meetings due to actual or apparent conflicts, there is room to refine how these conflicts are identified and the standards employed to judge permissible COIs.
Policy Recommendations
In an effort to better leverage Advisory Committee membership, the potential policy recommendations are as follows:
Committee Composition
- If there is flexibility and committee composition is not bound by law, include a patient representative and pharmacist and/or pharmacologist on each Committee
- Patient representatives provide a needed perspective due to lived experiences and understanding of how specific drugs and devices affect their day-to-day life
- Drugs and devices will usually pass through the hands of pharmacists and pharmacologists. Therefore, they should have the opportunity to serve on these Committees and provide feedback. Pharmacologists also understand the clinical application of drugs.
- Develop a register of temporary members that can be utilized when additional expertise is needed for Committee meetings or when there is a conflict of interest (COI)
Role of the Chair
- Expand the role of the Committee chair that will encompass the task of recruiting both standing and ad hoc members, as well as identifying prominent issues and products for Committee consideration, thereby allowing for specialized input from their Committee
Training and Regulatory Process
- Institute a basic 101 training for all newly appointed Advisory Committee members that covers statistical analysis, clinical trial design, and elucidates the partnership between the FDA and AdComm
- Include an overview of the regulatory process and how the FDA’s decision-making process is performed
COI Auditing Process
- Develop a process that can quickly replace individuals who have a known conflict of interest
- Clearly delineate criteria for committee service acceptance regarding individuals with potential or actual conflicts of interest
- Streamline the COI process to prevent duplicative work that may act as a deterrent to experts volunteering to serve on the AdComm (work with GSA on this matter if necessary)
Conclusion
Advisory Committees are pivotal to maintaining trust with the public. It is essential for public safety to ensure that the most qualified experts are selected to serve on these Committees and that they have the tools to provide the FDA with informed and evidence-based recommendations. In an effort to increase public health safety, the FDA should enhance the AdComm structure by expanding the chair’s role, creating training programs for all new Advisory Committee members, and revising the conflict of interest procedures.
Public meetings led by FDA Advisory Committees are instrumental in facilitating transparent deliberation between the FDA, the advisory body, and the American public.
Internal disagreements present a growing concern about FDA leadership overruling the expert opinions of scientific staff and proceeding with official approvals, thus undermining staff expertise, decreasing agency morale, and potentially diminishing public trust.