Namandjé N. Bumpus, Ph.D.
Chief Scientist, Food and Drugs
U.S. Food & Drug Administration
Dear Dr. Bumpus,
As members of the Patient, Consumer, and Public Health Coalition, we appreciate your responding to our July 12, 2023 letter to Commissioner Califf on December 7, regarding FDA scientists’ presentations in the materials provided to the public and FDA advisory committees. However, we want to clarify that our primary concern was not with the FDA approving drugs that the Advisory Committee members had voted against, but rather with FDA approving drugs that the agency’s own scientists had clearly stated did not meet the statutory standards for evidence of safety and efficacy.
As we discuss in detail below, we are very concerned when the final FDA decision overrules the opinions of the FDA’s own scientists. Such actions undermine the public trust and should be avoided, especially when the scientific staff are in consensus.
As a coalition comprised of nonprofit organizations representing public health experts, patient and consumer advocates, and health care professionals who are very familiar with the FDA approval process, we are well aware that the FDA Advisory Committees are advisory. We recommended better training for Advisory Committee members because we have frequently observed that some members are not very knowledgeable about the FDA regulatory process, the specific data being provided, or the statistical implications of the results. That is not our primary concern, however. Instead, our July 12 letter focused on our concerns about the increasing number of FDA approvals that are inconsistent with the presentations and materials provided by its own FDA scientific and statistical experts during these committee meetings. As we explained, it is especially concerning when Center Directors have publicly undermined or privately overruled the recommendations of their own scientists and statisticians, either for accelerated approval or full approval.
In our letter we provided numerous examples of such cases and therefore recommended that “Center Directors and other FDA officials attending Advisory Committee meetings refrain from making comments that can be interpreted as encouraging committee members to vote a particular way; when FDA officials attend these meetings, their remarks should make it clear that FDA wants to hear their views and not to influence their votes.” This point was not addressed in your response. In our meeting with Commissioner Califf on March 1, which you attended, the Commissioner expressed strong concerns about the growing lack of trust in FDA, particularly when FDA approved a product that Advisory Committee members had opposed. The goal of our letter was to point out that our primary concern was when Center Directors or other FDA officials spoke at Advisory Committee meetings prior to the vote, directly or indirectly urging members to vote in ways that conflicted with the FDA scientific and statistical presentations at those meetings, or subsequently privately overruled the recommendations of FDA scientific staff.
We agree with your statement that the FDA must reconcile differing perspectives and different conclusions when reviewing the same data. You stated, “FDA’s decisions are made based on its evaluation of the data after considering all the views expressed.” However, if the FDA wants to regain the trust of researchers, scientists, and policymakers, and keep the agency’s best scientific staff, it must be more respectful of its own scientists in public meetings as well as in its final decision-making. As Commissioner Califf pointed out at our March 1 meeting, it is the FDA scientists who have spent months reviewing the data. We agree with the Commissioner that Advisory Committee members have not spent nearly as much time reviewing the data, but it is equally true that the Center Directors have not either. It undermines public confidence when high level FDA officials focus on the need to be “flexible” as justification for disregarding the views of FDA scientistic staff that the evidence does not support safety and/or efficacy.
Regarding the FDA decision to grant accelerated approval to Elevidys, we were especially concerned that the FDA apparently did not take into account Sarepta’s failure to complete timely confirmatory trials on its previously approved treatments for the same disease (Duchenne Muscular Dystrophy).1 As a result of FDA’s earlier decisions regarding Sarepta drugs, families have spent millions of dollars over the last 7 years on treatments that are still not proven to work. In fact, there is now real-world evidence that patients who have taken the earlier Sarepta drugs are discontinuing treatment within months.2
Thank you for your clarification regarding the full approval status of the PI3K inhibitor duvelisib (Copiktra). However, we remain concerned that FDA issued a warning in response to an increase in deaths reported in post-market research, rather than rescinding approval after FDA scientists provided clear evidence of a higher death rate for Copiktra patients at the 2022 Advisory Committee meeting.3
In closing, we want to reiterate that our primary concern is not when the FDA overrules the FDA advisory committee recommendations, but rather those cases when the final FDA decision overrules the opinions of the FDA’s own scientists. Moreover, when FDA senior staff show a bias in favor of certain companies that is inconsistent with the concerns of most FDA scientists scrutinizing the data as well as concerns expressed by well-respected Advisory Committee members, it certainly undermines the public trust even more. Nevertheless, we want to make it clear that the most unacceptable solutions would be 1) to tamp down dissent at public Advisory Committee meetings by eliminating public meetings, 2) to select only Advisory Committee members who will support whatever position the FDA has already taken, or 3) to eliminate voting at FDA Advisory Committee meetings.
Sincerely,
American Medical Student Association – Wisconsin
Breast Cancer Action
Doctors for America
Government Information Watch
Jacobs Institute of Women’s Health
Medical Device Problems
MISSD
Mothers Against Medical Error
MRSA Survivors Network
National Center for Health Research
National Women’s Health Network
Patient Safety Action Network
TMJ Association
USA Patient Network
Washington Advocates for Patient Safety
Woodymatters
Click here for the full response letter from FDA.
Cc:
Dr. Robert Califf
Commissioner of Food and Drugs
U.S. Food and Drug Administration
Elizabeth Jungman
Chief of Staff, Office of the Commissioner
U.S. Food and Drug Administration
1.Bendicksen, L., Zuckerman, D. M., Avorn, J., Phillips, S., & Kesselheim, A. S. (2023). The Regulatory Repercussions of Approving Muscular Dystrophy Medications on the Basis of Limited Evidence. Annals of internal medicine, 176(9), 1251–1256. https://doi.org/10.7326/M23-1073
2. Hong, D., Avorn, J., Wyss, R., & Kesselheim, A. S. (2024). Characteristics of Patients Receiving Novel Muscular Dystrophy Drugs in Trials vs Routine Care. JAMA network open, 7(1), e2353094. https://doi.org/10.1001/jamanetworkopen.2023.53094
3. FDA Briefing Document. (2022). Oncologic Drugs Advisory Committee Meeting September 23, 2022. https://www.fda.gov/media/161692/download