Government Capacity

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

09.10.24 | 6 min read | Text by Cheri Banks

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. 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.

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: 

• Centers employing various mechanisms to disseminate dispute resolution Standard Operating Procedures (SOPs) to employees.
• Requiring Center SOPs for dispute resolution to clearly state that written documentation is the only avenue in which a formal dispute can be triggered (this step ensures appropriate historical documentation).
• Developing several avenues to address scientific issues through the use of regulatory briefings, advisory committees, internal discussions with Center Directors, standing subject matter committees, and multi-disciplinary teams. 

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.