Advisory Committees for the 21st Century Recommendations Toolkit

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 for the executive level, for the executive level, that may assist with enhancing the FDA’s ability to obtain valuable advice for evidence-based decision-making. In this toolkit, we build off of those discussions by providing you with actionable policy reform recommendations. We hope that these recommendations catapult the Advisory Committee structure into one best suited to equip all AdComms with the necessary tools needed to continue providing the government with the best advice.

Download a PDF version of these recommendations on the left.

Recommendations and Best Practices for Actionable Policy Implementation

Voting for FDA Advisory Committees

Update Type: Process

Best Practices for Implementation 

The United States Food and Drug Administration can uphold their voting mechanism by updating their document entitled, “Guidance for FDA Advisory Committee members and FDA staff: Voting Procedures for Advisory Committee Meetings” to include language that clearly states a vote should be taken at all Advisory Committee meetings where a medical product is being reviewed. This guidance should also indicate that the absence of voting should only occur if an Advisory Committee meeting has been convened to discuss issues of policy. Further, this guidance should be considered a level 2 guidance as it falls into the category of addressing a “controversial issue”. To effectuate these changes, a notice of availability (NOA) may be submitted to the Federal Register for public input (public input is not a requirement before implementation). 

Potential Language to be Utilized for Guidance 

In an effort to continue to allow Advisory Committee members to provide unbiased, evidence-based feedback and uphold such an integral part of the Advisory Committee process, voting is hereby mandatory for all Advisory Committee meetings that are convened where the purpose is to review and assess the safety and efficacy of medical products. 

Involved Stakeholders

In order for this process to successfully occur, the FDA will need to amend their guidance with the aforementioned updates. Consideration should be given to incurred costs for personnel required to complete these updates. Personnel needed for these amendments may include, but are not limited to, the (a) Office of the Commissioner, Office of Clinical Policy and Programs, Office of Clinical Policy, (b) Center for Devices and Radiological Health, (c) Center for Biologics Evaluation and Research, and (d) Center for Drug Evaluation and Research.

FDA Staff, Leadership, and AdComm Disagreements

Update Type: Process

Best Practices for Implementation 

Implementing these recommendations will improve conflict resolution internally and between the Agency and Advisory Committee members. Best practices for implementation include (a) building the Scientific Dispute Resolution at FDA guidance into the official FDA onboarding process for new hires to raise awareness, (b) provide annual employee trainings in an effort to stay up-to-date with dispute resolution processes and procedures, and (c) develop a guidance that delineates the process for resolving conflicts between the Agency and Advisory Committees when there are differing opinions. 

Note: Guidance for resolving disputes between the Agency and Advisory Committees should be submitted to the Federal Register for public comment. Guidance should also include plain language that designates the avenue to be used for official decision notifications, the timeliness of these notifications after convenings have concluded, and circumstances in which the FDA cannot notify Advisory Committees that their decision is in direct opposition of the Committee’s vote (e.g., – if this notification would breach a confidentiality agreement with the applicant). Implementing a transparent process to communicate with AdComm members regarding differences between the Agency and the AdComm will assist in improving morale between both parties, but also encourage continued support of the AdComm.

Involved Stakeholders 

Successful implementation of these recommendations will require the capacity of human resources personnel and individual center leadership. 

Update Type: Regulatory

Best Practices for Implementation

Center leadership can assign FDA staff to make the necessary guidance amendments which should include the requirements for inclusion in the onboarding of all FDA employees. Staff should also be responsible for obtaining feedback on amendments from all necessary internal parties and submitting proposed amendments to OMB for review and addition to the Federal Register. Federal register comments will then be reviewed by FDA staff, guidance will be updated accordingly, and a final draft submitted to OMB for review. If approved, the final regulation will be published in the Code of Federal Regulations. Congressional involvement should not be necessary.

FDA Center leadership should delegate the task of creating an annual mandatory training program for all FDA employees to review this guidance in an effort to stay abreast of the procedures for dispute resolution. 

Involved Stakeholders 

FDA Center leadership, FDA staff, and the Office of Management and Budget (OMB) are the intended stakeholders for implementation of these recommendations. To incorporate this guidance into FDA regulations, Center leadership will need to assign FDA staff to amend guidance and submit to OMB.

Leveraging AdComm Membership

Update Type: Process

Expanding Committee Representation

Amplifying the Role of the Chair

Establishing Training and Regulatory Procedures for Incoming Members

Best Practices for Implementation

With respect to Committee composition, the FDA should consider adding patient representatives to all Committees that review medical products. The addition of a patient representative will ensure that the voice of the population who the medical product affects is heard. The FDA can select individuals best suited to fill these roles through connecting with patient advocacy organizations. If patient representatives are selected, the FDA should develop an onboarding program to familiarize the patient representative with basic knowledge of the federal regulation process. This program should educate the patient representative on (a) the types of questions presented to Advisory Committees, (b) how the FDA views the role of the patient representative in the process, (c) the internal review process for data that is submitted, and (d) other pertinent topics related to medical product regulation.

Leveraging the role of the Advisory Committee Chair can help the FDA fully optimize the use of their Committee. “Chairs possess extensive networks that could support the identification of permanent or temporary expert participants for AdComms” (Banks, 2024). Allowing Chairs the ability to identify relevant issues or products for their respective committees to review can provide an additional layer for the FDA to keep abreast of critical public concerns via appropriate committee evaluation (Banks, 2024).

Finally, while Committee members may be experts in their own right, training should be provided for all. The FDA should provide basic 101 training courses that can cater to the needs of members with various knowledge bases. Training should include information on the relationship between the FDA and Advisory Committee members, best practices for understanding statistical analysis, and the different types of clinical trial designs. Training should provide real-world examples of statistical analysis and trial design in use (this can be done by providing examples from prior medical product review). 

Involved Stakeholders

FDA Center staff (including statisticians and scientists for the development of training programs).

Conflict of Interest (COI) Auditing

UPDATE TYPE: PROCESS 

Best Practices for Implementation

To prevent recurring COIs, the FDA should develop a database of experts for various categories of expertise that can be selected to replace those with known COIs. This database should include names, contact information, credentials, all areas of expertise for each expert, and should link to public financial interest databases that can serve as a source for identifying conflicts (e.g., Open Payments, Dollars for Docs).

To prevent public confusion, the FDA should amend their Guidance for the Public, FDA Advisory Committee Members, and FDA Staff: Public Availability of Advisory Committee Members’ Financial Interest Information and Waivers to specify circumstances that warrant a COI waiver being administered. This will increase transparency and help Advisory Committee members and the public understand the reasoning in allowing members with conflicts to participate in meetings. This guidance can then be submitted to the Federal Register for public comment

UPDATE TYPE: PROCESS | REGULATORY

Best Practices for Implementation

Streamlining the COI process will assist the FDA with retention efforts for Advisory Committees while maintaining compliance with conflict of interest regulations. A digital system should be developed that allows Advisory Committee members to select whether their financial information has changed through the use of a dropdown or check box. This will prevent duplicative work and also contribute to a sustainable (green) process.

Involved Stakeholders

The Office of the Commissioner, Office of Clinical Policy and Programs, Office of Clinical Policy would be the interested stakeholder to issue updates to the COI policy and would work with the General Services Administration if necessary. 

The Role of Patient Advocacy in the AdComm Process

Update Type: Process

Best Practices for Implementation

Public comments are a crucial part of the regulatory process. The FDA should focus on increasing participation in this process, as well as notifying participants of what should be expected from the public comment period. By law, the FDA must allow a public comment period for all Advisory Committee convenings. To increase participation, the FDA should allow public comments to be vocalized in-person and virtually, in addition to the submission of public comments to the docket. 

Regarding Committee composition, please refer to Best Practices for Implementation under Leveraging AdComm Membership for information on the addition of patient representatives to Advisory Committees (see prior section above).

Patient engagement in the regulatory process is necessary to inform evidence-based decisions. While the FDA currently has ways to engage these communities through the use of public comment and initiatives such as Patient Focused Drug Development (PFDD), engagement should be an ongoing process. As mentioned, the FDA can develop and leverage existing relationships with public health agencies and advocacy organizations who can then serve as the liaison of feedback to the FDA. The FDA can also consider expanding their current initiatives and programs to engage communities twice a quarter instead of quarterly or annually. Consistent engagement in this form will help to establish trust between the FDA and the public who they serve, as well as give them the needed information from the communities who are most impacted from their decisions.  

Involved Stakeholders

Implementation of these recommendations and expansion of current initiatives will require the involvement of FDA Center leadership and Center staff.

Improving Public Awareness and Understanding of Advisory Committees

Update Type: Process

Best Practices for Implementation

The FDA should develop a monthly content plan to utilize its current interactive and social media outlets and disseminate information related to the role of Advisory Committees and their convenings, while also maintaining compliance with the FDA’s social media policy. The social media content plan should be centered around (a) what an Advisory Committee is, (b) how members are selected, (c) information regarding votes of Advisory Committees and how they are specific to safety and efficacy, but are not voting on the approval of a medical product, (d) discussing upcoming Advisory Committee meetings, their location, and inviting the public to participate via public comment, (e) sharing information about what a public comment is, requirements for making public comments, and how the FDA reviews them, and (f) sharing a webpage where the general public can input their personal email to be notified of upcoming Advisory Committee meetings.

FDA staff should develop a plain language disclaimer to be placed on all social media posts, meeting materials, and websites related to Advisory Committees. This disclaimer should illustrate that Advisory Committee members will provide unbiased expertise to assist the FDA with their decision. However, while the Committee’s vote is included in consideration for the decision, their vote is non-binding which leaves the FDA as the final decision maker for approval.

Finally, the FDA should identify state/local public health agencies, as well as advocacy organizations that they can potentially partner with to disseminate information more broadly. These agencies and advocacy organizations have strong relationships with various communities who should be engaged in the regulatory process. Developing a relationship with these agencies and organizations in an attempt to engage the community will assist the FDA with building connections and trust, as well as mutual understanding of Advisory Committee roles. Potential partners can be identified using the linked list under involved stakeholders. 

Involved Stakeholders

Implementation of these recommendations and expansion of current initiatives will require the involvement of FDA Center leadership, Center staff, Office of External Affairs (OEA) Web and Digital Media staff, Office of Information Management and Technology (OIMT), state/local public health departments, and advocacy organizations.

Note: These listings of state/local public health departments and advocacy organizations are intended to be used as a starting point in the identification of potential partners and not to be considered an exhaustive list.

For questions related to this toolkit, please contact

Cheri Banks
Health Regulatory Specialist
cbanks@fas.org

Grace Wickerson
Health Equity Policy Manager
gwickerson@fas.org

Improving Public Awareness and Understanding of Advisory Committees

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 are presented in case study format detailing the recurring themes that emerged and policy recommendations for improvement.

The FDA holds one of the most important roles as a federal agency which is to ensure public safety when approving vaccines, medical devices, and medicines. The approval of these products usually require extensive trials with data that supports their safety and efficacy. Considering that most of these decisions are complex and multifaceted, the FDA enlists the support of Advisory Committees to assist with their decision-making process. The primary role of FDA Advisory Committee members 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. Although AdComm members serve the FDA in an advisory capacity, their recommendations are non-binding. Therefore, they do not have the final say in the regulatory approval process. 

However, over the years, it has been made evident that the public is unaware of the role of Advisory Committees and ways in which they can engage with the FDA. In this case study, FAS hopes to share the current problem and actionable recommendations to combat public misconceptions regarding FDA AdComm roles and provide guidance on increasing FDA engagement with the public and other relevant stakeholders throughout the regulatory process.

Public Awareness Problems

While AdComm members are experts in their respective fields and volunteer their time to provide advice to the FDA, there are multiple factors that must be considered before making official decisions. The recommendations provided during Advisory Committee meetings are just one aspect that is considered for regulatory decision-making and do not guarantee an official approval or denial of a product by the FDA. During AdComm meetings, the FDA allows the general public to make public comments to the Agency and the AdComm regarding the topic that is being addressed. Despite this, members of the general public have expressed that, on many occasions, they are unaware AdComm meetings are occurring. This, in effect, deprives them of the opportunity to communicate directly with the FDA and the AdComm. Additionally, they feel the FDA fails to engage them in an adequate manner, thereby limiting opportunities for participatory engagement. It has also been noted that most members of the general public are unaware FDA Advisory Committees exist; and, for those who are aware, they are unclear about the capacity of their role within the regulatory process. 

For these reasons, the FDA must take measures to enhance public understanding in an effort to combat misinformation, educate, and raise awareness on the existence of Committees and their purpose.  

Communicating AdComms to the Public

Improving Public Awareness of Advisory Committees and their Role

Improving public awareness on the existence of FDA Advisory Committees and their purpose would assist the FDA with improving public trust and debunking myths and misinformation related to the approval of medical products. Advisory committees operate as an independent party and their recommendations assist with guiding regulatory decision-making. However, their recommendations are non-binding, and FDA leadership must consider additional factors before granting approvals or denials of medical products. 

To increase public awareness on Advisory Committees, it should be made clear that AdComm recommendations are not conclusive, as the FDA considers multiple factors in its official decisions. The FDA can leverage social media platforms to increase awareness and understanding of AdComms through the use of disseminating information via the use of ads and active social media engagement. A survey conducted by Pew Research Center states that eight in ten Americans believe social media platforms are an effective way to bring awareness. In addition, disclaimers should be included on all public facing materials referencing AdComms to indicate their purpose. Clearly communicating this to the public will dispel myths that AdComms make the final call on the approvals of medical products. 

Improving Communication about Advisory Committee Meetings

Encouraging public participation for Advisory Committee meetings will help foster a collaborative and engaged general public who can contribute valuable life experience to the regulatory process. FAS has identified ways in which the FDA can better communicate with the public to inform them of Advisory Committee meetings. First, the FDA can develop a webpage that allows people to receive notifications of upcoming AdComm meetings. The FDA can also establish relationships with state and local public health agencies, as well as advocacy organizations to spread awareness. Through these relationships, the various agencies and organizations can use their networks to disseminate widespread information on AdComm meetings. Public health agencies and advocacy organizations can gauge the best ways in which these communities would like the FDA to engage with them. This understanding of the communities they serve makes them an ideal partner for fostering continuous engagement.  

Policy Recommendations

In an effort to improve public awareness and understanding of AdComms, the potential policy recommendations are as follows: 

Conclusion

Advisory Committees are essential to the FDA regulatory decision-making process. It’s imperative that their role is understood by them and the general public to best move the needle forward. While the FDA currently allows the public to provide public comment at Committee meetings, that alone cannot be considered engaging the community. The FDA must create new opportunities for interpersonal communication which will create an environment of mutual trust and understanding between both parties.

The Role of Patient Advocacy in the AdComm Process

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 are presented in case study format detailing the recurring themes that emerged and policy recommendations for improvement.

The regulation of medical products is the responsibility of the Food and Drug Administration (FDA). To ensure effective decision-making regarding these products, the FDA recognizes the importance of patient advocacy and the perspectives of patients. In 1988, the FDA initiated the patient engagement process through the Office of Aids Coordination, and within five years, the first patient representative was appointed to an FDA Advisory Committee. Since then, the FDA has significantly enhanced its methods of engaging patients, caregivers, and patient advocates. This includes the establishment of various offices, programs, collaboratives, listening sessions, public guidance, and more.

The Evolution of Patient Engagement at the FDA

The FDA employs several avenues to engage patients in the regulatory process. Some avenues include the Patient Engagement Advisory Committee (PEAC), public comment, the Patient Focused Drug Development Initiative (PFDD), the Patient Listening Session Program, Patient Engagement Collaborative (PEC), and the Patient Representative Program (PRP). This list does not cover all the ways in which the FDA engages patients and advocates but provides an overview of the key operations involved in patient engagement efforts. 

The Patient Engagement Advisory Committee is the only Committee that is completely composed of caregivers, patients, and patient representatives from various organizations, as a way to ensure that the lived experiences of these populations and their opinions are included in the deliberations and regulatory decision-making of medical products. Public comment is a requirement by law for federal agencies, allowing the public to provide feedback on proposed actions or new rules and regulations. Public comment is also sought during Advisory Committee meetings to gather information and perspectives from the public. PFDD meetings provide a platform for the FDA to obtain insights from patients on specific diseases and their treatments. To identify the issues most important to patients, the FDA has a series of guidance documents that are used specifically for PFDD meetings. 

The Patient Listening Session Program facilitates informal meetings between patients, their representatives, and FDA staff. These sessions cover a range of topics, including treatment preferences, quality of life, unmet medical needs, and the impact of diseases and their symptoms. The PEC offers a forum for patients, caregivers, and advocates to discuss patient engagement operations. Lastly, the PRP allows patients, caregivers, and advocates who serve as special government employees the opportunity to provide advice to the FDA’s Commissioner or a designated representative on matters related to medical devices and their regulation.

Although there are various avenues for patient engagement and advocacy participation in the medical product regulation process, there are also ways in which these avenues can be expanded or improved.   

Patient Advocacy Problems

For many years, patients and their caregivers have not seen significant or sustainable treatments that have been developed to treat many illnesses and diseases. Some treatments have proven to be ineffective yet still made it to market approval. On the other hand, there are treatments that met safety and efficacy standards but were not approved. There are also those treatments that are simply not affordable to the populations that need them most. In many of these scenarios, the patient representative voice was lost as they did not have the option to express their concerns or perspectives on certain treatments with decision makers. This further confirms that the role of patient advocacy and allowing space for the patient representative voice is crucial to the regulation process of medical products. 

At the moment, the patient voice is not always heard because there are some FDA Advisory Committees that do not have a patient representative.

While the role of patient advocacy is crucial, it is important to note there should be boundaries in which patient perspective is considered for decision-making. Although patients and their advocates seek treatments that better address their needs, this desire can sometimes obscure their judgment concerning long-term treatment effectiveness. Frequently, patients and their supporters present powerful arguments to Advisory Committees and the FDA for approval of particular medical products which can lead to expedited medical product approval in the absence of supportive evidence. 

The endorsement of eteplirsen, which was intended for the treatment of Duchenne muscular dystrophy (DMD), illustrates this point. Despite a 7 to 3 vote by the FDA’s Advisory Committee against approval due to insufficient evidence of its benefits, opposition from the FDA’s Center for Drug Evaluation and Research’s former leader resulted in the drug’s authorization. This sparked substantial internal and public criticism and led Dr. Ellis Unger from the FDA’s Office of Drug Evaluation to challenge the approval decision. Dr. Unger emphasized that “patient-focused drug development is about listening to patient perspectives about what matters to them; it is not about basing drug approvals on anecdotal testimony that is not corroborated by data.”

This approval was perceived by many as having been heavily influenced by patient advocacy and raised concerns about potential long-term implications for patient health. It also signaled a need to further examine both patient education and the appropriate limits of patient involvement in the regulatory process. This could have been mitigated had there been a list of criteria in place to be followed for public comment. 

Incorporating Patient Perspectives

The Food and Drug Administration (FDA) is committed to understanding the balance of benefits and risks acceptable to patients as they relate to medical products. The FDA defines the role of patient representatives that serve on Advisory Committees as “Special Government Employees” who provide direct input to agency staff and share valuable insight on their experiences with various diseases, conditions, and devices while gaining access to confidential information. These representatives are selected by the FDA to serve on Advisory Committees using a specific set of criteria including, but not limited to: 

This criteria ensures the FDA will understand the patient perspective as it relates to various medical products and ensures those selected to serve on Advisory Committees are knowledgeable about the areas in which they are aiming to provide guidance. Currently, there are some FDA Advisory Committees that do not have a patient representative. Further, the patient representatives serving on committees do not always have voting privileges. The absence of consistent voting privileges for some patient representatives on Advisory Committees and not having a standing patient representative on all committees hinders these individuals from providing an official stance on behalf of the community they represent. Additionally, public comment plays a significant role at Advisory Committee meetings by permitting individuals—including patients, caregivers, and advocacy organizations—to highlight concerns and propose solutions that may not have been previously considered by decision-makers. This process also helps the committee and agency gauge patient acceptance or opposition related to medical products, thereby enhancing their ability to make decisions that more accurately reflect public needs. 

When Sarepta was seeking approval of eteplirsen for the treatment of DMD, a patient advocacy organization brought hundreds of patients, caregivers, and other advocates to the Advisory Committee convening so they could make a public comment to the Committee and the agency. Shortly after, the drug received a swift approval. Although it presented much controversy within the agency and the public, it showed how influential patient advocacy can be. Personal lived experiences, compelling stories of debilitating illnesses, and experiences with current treatment have the ability to impact regulatory decision-making. 

The role of patient advocacy continues to be important in the Advisory Committee process and FDA regulatory decision-making process because it is crucial to assisting with decisions that affect the American public. Patient advocacy can be presented in the form of patient representatives that serve on Advisory Committees, those who make public comments during Advisory Committee convenings, and various outreach programs by advocacy organizations. The role of advocacy gives patients and caregivers support, promotes and protects their rights, and allows broader visibility for the issues that are most important to them. All of these avenues for patient perspective are important to understand how treatments perform, the current needs of the patient population, and how to tailor care for these populations by truly understanding their condition, diagnosis, and current management. Therefore, their voice is critical to truly understanding how various medical products will benefit their population, how they will access and afford these products, and how they will fill an unmet medical need.

Policy Recommendations

In an effort to better leverage Advisory Committee membership, the potential policy recommendations are as follows: 

Conclusion

The landscape of disease burden and associated symptoms is ever-evolving. To ensure the FDA is best prepared for this changing landscape, patient advocacy and amplifying the patient voice should be considered vital to the development and regulation of medical products. Involving those who are the most impacted by these products is essential. The FDA can further promote the patient perspective and advance patient-centered health through incorporating patient representatives on all Committees that are reviewing medical products, making patient engagement an ongoing process, hosting town halls for patients to allow a broader audience the opportunity to voice opinions, and having dedicated staff to sort through public comments from patients.

FDA Staff and Leadership Disagreements and the Role of the AdComm in the Regulatory Process

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 are 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. However, there are instances when disagreements arise between the agency’s scientists, statisticians, Advisory Committees, and leadership on the accelerated or full approval of medical products. The resolution of these 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.

When Disagreements Between FDA and AdComms Arise 

The Federal Advisory Committee Act governs the FDA’s Advisory Committees and establishes a process in which the FDA can seek expert advice on various issues related to science, regulatory policy, and the evaluation of products under the FDA’s jurisdiction. When the FDA has differing opinions on safety and efficacy requirements of medical products, certain products may be referred to an Advisory Committee for further data review by an impartial entity. To aid in this matter, the FDA has developed guidance detailing the process for assembling Advisory Committees. Since the resources required for convening these committees are significant, the FDA ensures there is substantial uncertainty or disagreement regarding the data. Advisory Committees will discuss the evidence and provide feedback with the goal of producing the most optimal evidence-based resolution. This part of the regulatory process is crucial to the agency’s regulatory decision-making as it involves unbiased parties and leads to transparency, upholding public safety, and maintaining public trust. However, there are times that FDA leadership disagrees with the votes of their Committees and proceeds with controversial approvals. One example of this scenario was approval of the drug Aduhelm. Aduhelm, which was marketed as a treatment for Alzheimer’s, received an overwhelmingly negative vote from the Advisory Committee to move forward with its approval for market distribution. Ten of eleven Committee members stated the data did not support adequate efficacy for approval. Nonetheless, the FDA granted accelerated approval, sparking resignations from a third of their Committee and outrage amongst the public. This disregard for expert opinion was viewed as the FDA exhibiting an approval bias, a perspective the public currently maintains of the FDA. 

In 2023, various organizations and coalitions, such as Doctors for America, Jacob’s Institute of Women’s Health, National Center for Health Research, TMJ Association and more publicly expressed concerns regarding the FDA’s leadership and their approach to drug approvals through a letter addressed to the FDA’s Chief Scientist, Dr. Namandje N. Bumpus. They highlighted FDA leadership had ignored claims by scientific staff that safety and efficacy standards were not being met for the drug Elevidys. Manufactured by Sarepta Therapeutics, Elevidys was granted accelerated approval by FDA leadership. Dr. Bumpus responded to this letter defending the FDA’s approval of Elevidys by referring to the agency’s comprehensive review of the data and consideration of the potential risks of the approved treatment, nature of the disease and its impact on patients, and the limited amount of therapies available. However, the response did little to quell public scrutiny of the controversial approval. Critics were apt to point out that the FDA had a record of approving products in this manner. Years prior, the FDA had approved the drug Eteplirsen for the treatment of duchenne muscular dystrophy (DMD), despite the objections of their scientific staff which disclosed a lack of evidence for the efficacy of this treatment. Criticism was also directed at FDA leadership suggesting the approval of some medical products were potentially due to favoritism toward companies seeking approval.

Resolving Internal FDA Disagreements

While it is acknowledged that the FDA must consider technological and political implications alongside scientific evidence in decision-making, it is essential to address the concerns of these organizations and coalitions. As part of an ongoing project to reform the FDA’s Advisory Committee system and assist the FDA with getting the advice needed to make the best evidence-based decisions, FAS engaged in discussions with current and former Advisory Committee members to seek their input on resolving disagreements between FDA staff and leadership. These conversations highlighted the breach of trust between the FDA, its staff, and the public.

Quotes from Experts

“FDA leadership needs to make is clear what data was used and why they’re moving forward when there is opposition”

“Disagreements should be addressed by a non-biased source because it affects the public safety.”

“There will be times where there are disagreements between staff and leadership. However, there’s a critical need for transparency within the FDA about why decisions are made. These are not decisions about evidence only. Ever.”

“Disagreements should be a matter of public scrutiny. There should be transparency that doesn’t jeopardize confidentiality.”

The FDA’s Commissioner has acknowledged the lack of trust within the institution and expressed a commitment to address the issue. There are many reasons for the lack of trust. However, one reason stems from the FDA’s approval of medical products despite clear opposition from its scientists and sometimes Advisory Committee members.

This raises the question of how the FDA intends to address these internal disagreements, which have the potential to impact the health and safety of the American public. Currently, the FDA has implemented a program called Scientific Dispute Resolution (SDR) to handle such conflicts. This document was initially developed in 2009 and recently updated in 2021 with the purpose of outlining the process for communication regarding internal scientific disputes within FDA Centers. It defines scientific disputes as disagreements that arise from the interpretation of science and the resulting decisions. This definition clearly distinguishes the circumstances in which the guidance should be utilized to resolve discrepancies between FDA scientists, statisticians, and their respective Center leadership. The guidance offers valuable examples of best practices for resolving formal and informal scientific disputes within the agency. Some of those best practices include, but are not limited to: 

However, it should be noted these best practice recommendations are not obligatory and their adoption is left to the discretion of the individual Centers. Furthermore, the document provides a process by which any of the internal parties involved can appeal the resolution of their dispute if they find it unsatisfactory through the Office of Research  Integrity at Health & Human Services (HHS).

Policy Recommendations

To increase morale and improve the approach and resolution of internal disagreements within the agency, the policy recommendations are as follows:

  1. Ensure that all FDA staff and leadership are fully cognizant of the existence and details of the Scientific Dispute Resolution at FDA guidance and the process for submitting disputes for review.
  2. Incorporate the Scientific Dispute Resolution at FDA guidance into FDA regulations
    1. Note: To incorporate this guidance into FDA regulations, the FDA will propose the regulation for OMB review. OMB will review and open the regulation up for public comment through the Federal Register. Responses to comments will be developed, and a final draft submitted to OMB for review. If approved, the final regulation will be published in the Code of Federal Regulations (Congressional Research Service, 2013). The involvement of Congress will not be necessary.
  3. Amend the Scientific Dispute Resolution at FDA guidance to dictate the mandatory execution of best practices within the dispute resolution process.
    1. This guidance should identify additional non-biased parties (that may not be government-affiliated) to provide impartial guidance on complex scientific matters affecting public safety. 
  4. Develop guidance that clearly explains a transparent process to communicate effectively with AdComm members regarding decision making when parties have opposing viewpoints
    1. Implementing a transparent process to communicate with AdComm members regarding differences between the agency and the AdComm will assist in improving morale between both parties, but also encourage continued support of the AdComm.
    2. This recommendation is also supported by a survey conducted by 3D Communications with 400+ AdComm members where 94% of members concurred that the FDA should develop a process to communicate their reasoning for decisions in opposition to Committee recommendations (3D Communications, 2024).

Conclusion

While FDA leadership ultimately holds the authority to grant approvals, it is crucial that the perspectives of all experts are duly considered. This includes the valuable input from the agency’s scientists, statisticians, and advisory committees. To regain public trust and restore integrity, it is imperative to first rebuild trust internally among the dedicated public servants within the FDA. Adoption of the aforementioned recommendations would start the trust-rebuilding process and lead to increased safety and precaution measures when approving drugs and medical devices.

Leveraging AdComm Membership

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 are 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.

Quotes from the Committee
“There should be basic training for all laypeople on the committee. This would help to prepare them for fulfilling their duties.”
“There should be an orientation that explains the relationship between the advisory committee and the FDA, and how the FDA thinks about this process.”

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

Role of the Chair

Training and Regulatory Process

COI Auditing Process

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.

The Future of Voting for FDA Advisory Committees

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 are presented in case study format detailing the recurring themes that emerged and policy recommendations for improvement.

Advisory Committees (AdComms) serve as the core for expert engagement in the Food and Drug Administration’s (FDA) decision-making processes. These committees 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. Public meetings led by the FDA with these committees are instrumental in facilitating transparent deliberation between the FDA, the advisory body, and the American public. This practice helps to cultivate a collaborative environment between the FDA, the AdComms, and the public. AdComm recommendations are integral to strengthening public trust and reinforcing the FDA’s credibility. This relationship is corroborated by aligning the counsel of these independent entities with the FDA’s regulatory actions.

Key Problems Facing Advisory Committees

A critical component of the AdComm structure is its voting mechanism, a method by which hand-selected experts offer expert advice or recommendations on questions that have been proposed by the FDA to assist with informing its formal, regulatory decision-making. These questions include a broad range of topics, from evaluating post-market safety data to assessing pre-market product risks and benefits, and gauging whether a product should be approved or withdrawn from the market. The outcomes of the votes serve as barometers for the AdComms official stance on products and provide the FDA with a comprehensive and collective viewpoint. However, the recommendations proposed by AdComms are suggestive rather than prescriptive; ultimately, leaving the final decision to FDA leadership. 

Recent patterns indicate a reduction in the convening of AdComm meetings. In 2010, 55% of FDA-approved drugs were referred to an advisory committee. By 2021, the percentage of FDA-approved drugs with an advisory committee referral had dropped to 6%. The decline of meetings eliminates opportunities for evidence-based evaluation and deliberation that could potentially affect the health and well-being of Americans. Furthermore, the diminishing of these crucial interactions between the FDA, AdComms and the public exacerbates the lack of trust and erodes transparency. Interestingly, while most committees present definitive votes that are supported by explicit justifications for either approving or rejecting items under review, FDA Commissioner Robert Califf has suggested in multiple interviews that AC votes can be useful but are not mandatory for every meeting. This viewpoint raises concerns about the potential removal of voting from the reform agenda, which could undermine AdComms capacity to evaluate intricate topics that affect the American public consumer base. In addition, a survey conducted by 3D Communications with 400+ current and former AdComm members asked about the importance of voting. Results showed that 95% of AdComm members believe that voting should be retained when reviewing the benefits and risks of medical products. Reform discussions have materialized due to these factors, in addition to the FDA’s accelerated approval of Adulhelm (aducanumab) despite clear AdComm opposition. Demand for reform is inevitable and many are urging for there to be an increased number of AC meetings and a thorough reorganization of advisory committee operations and voting protocols. Such reform is not only administrative but also symbolic. This type of reform confirms that decisions affecting public health should be informed and shaped by multidisciplinary expertise. Additionally, it re-establishes the pivotal role of public input in regulatory affairs, which is an indispensable component to maintaining the American public’s trust.

Significance of AdComm Voting

In response to this call for AdComm reform, a project spearheaded by FAS has sought feedback from AdComm members regarding their views on the significance of voting. The intention of engagement is to understand members’ experiences as experts and their perspectives on voting by asking the following questions:

These questions aimed to measure the variability in voting mechanisms across committees and the value members place on voting. Results from 30 participants demonstrate a consensus on the critical role of voting in formulating committee recommendations, with 87% of committee members indicating a five (very important) as their stance on the importance of voting.

Policy Recommendations

To uphold the FDA’s integrity and regain public confidence, retaining voting at AdComm meetings is essential in addition to other recommendations to enhance the advisory committee process. The recommendations are as follows: 

Conclusion

The recommendations of FDA Advisory Committee members are a pivotal component to the FDA’s regulatory decision-making process. Maintaining the voting protocol for Advisory Committee meetings is essential as members strive toward the continued provision of precise, impartial, and evidence-based counsel to the FDA. This voting mechanism guarantees the inclusion of each member’s perspective and ensures that an official committee stance is taken, offering the FDA definitive and straightforward guidance.