US FDA Adcomm Reform Ideas: Neutral Facilitator As Chair, Public Hearing Lottery Process Tweaks :: Pink Sheet

The US Food and Drug Administration should consider using a neutral facilitator to lead advisory committee meetings and reconsider the lottery process for open public hearings.

The agency may also consider asking adcomm members to rate the strength of a drug’s efficacy and safety evidence on a numerical scale, either in addition to or instead of the formal benefit-risk vote, stakeholders said in comments to the agency.

The comments follow the FDA’s June listening session held in connection with the ongoing reform of the adcomm process. The agency sought feedback on several issues, including adcomm composition, service on the panels as a special government employee, and public perception and understanding of adcomms. (See also “US FDA Adcomm Reform: Does Listening Session Suggest No Major Near-Term Changes?” – Pink Sheet, April 29, 2024.)

Neutral facilitator

The proposal for a neutral facilitator to lead meetings, if adopted, would fundamentally change the long-standing approach where the panel leader, usually a scientific or clinical expert, leads the meeting.

That approach would also go further than the position taken by FDA Oncology Center of Excellence Director Richard Pazdur, who has said the panel chair should act as a moderator, proactively drawing committee members into the discussion. (See also “The Wait Is Over: US FDA Advisory Committees Returning To In-Person Meetings Come Fall” – Pink Sheet, Feb 26, 2024.)

“Also consideration should be given to the benefits of having a neutral facilitator in charge of Advisory Committee meetings, a role currently filled by the Chair, typically an expert scientist, not an expert in creating fair and meaningful conversation to inform regulatory decisions,” the EveryLife Foundation for Rare Diseases said.

Having a professionally trained meeting facilitator act as a non-voting committee chair “would ensure uniformity in meeting facilitation across committees and would also allow all voting experts to focus on the meeting content and scientific discussion.” – SSI strategy’s PharmApprove

“In several cases, we heard from community members who have witnessed advisory committee discussions dominated by one member’s perspective or derailed by less precise concerns that point discussions in one direction without the opportunity for others to step in and ensure a full picture of the problem is painted,” says the advocacy group for rare diseases.

“Expert facilitators are used in settings across public and private life to guide conversations, draw out key points and ensure meeting objectives are met. FDA should also consider the benefits of deploying them for advisory committee discussions.”

Having a professionally trained meeting facilitator act as a non-voting committee chair “would ensure uniformity in meeting facilitation across committees and would also allow all voting experts to focus on the meeting content and scientific discussion,” said SSI Strategy’s PharmApprove , a strategic communications company. in comments.

“FDA should either develop independent staff (ie, FDA staff who do not report to the center/department heads who administer the reviews) or engage outside professional meeting facilitators skilled in providing inclusive and objective discussion,” PFDDworks, a collaborative between patient advocacy leaders engaged in patient-focused drug development activities, said in his comments.

Adjustment of the OPH lottery

FDA heard calls at the listening session for changes to the open public hearing. Patients called for more emphasis to be placed on their experience with a disease or an experimental drug, while consumer groups and academic groups said that people who did not experience benefits from an experimental drug should also be heard. (See also “US FDA Advisory Committee Open Public Hearing Changes Urged” – Pink Sheet, July 5, 2024.)

Written comments suggested methods to maximize the time allocated to OPH, including changes to the lottery process used when the number of people wishing to speak exceeds the allotted time.

To encourage the broadest possible participation, the OPH timeframes and lottery process should be consistent across FDA Drug and Biologics Center Advisory Committees, “with every effort to extend the OPH time to provide ample speaking opportunities for registrants,” Pharmaceutical Research and Manufacturers of America’s comments. “More specifically, the time dedicated to OPH should reflect the duration of the entire AC meeting.”

OPH is the only time that patients who have participated in a study, patients and families living with the disease, patient organizations and others can weigh in with context that can support agency decision-making, the EveryLife Foundation said.

The current OPH lottery approach “does not result in a diverse and representative array of speakers that can cover the universe of perspectives relevant to regulatory decisions.” – EveryLife Foundation for rare diseases

“The limited time provided for such comments results in the agency conducting a lottery to assign speaking slots,” the group said. “The lottery approach, while understandable, does not result in a diverse and representative pool of speakers that can cover the universe of perspectives relevant to regulatory decisions.”

“A more targeted approach would be to consider a hybrid process that identifies key categories of stakeholders for each meeting and allocates a reasonable amount of time to each meeting,” EveryLife’s comments said. “In cases where demand exceeds the availability of these places, then a lottery approach may be initiated. This, along with providing the public with further clarity about the rules of OPH, how speakers are selected and safeguards how members of advisory committees should consider such testimonies , will go a long way toward public trust and understanding of the agency’s decisions.”

Similarly, the patient advocacy group I AM ALS said that while the use of a lottery system for OPH speakers has served the agency well in preventing bias, “we find that this method does not guarantee diversity of perspectives. Instead, we recommend a possible shift to have categories and conduct a lottery within those categories. For example, people who want to speak will classify themselves into a category and then be in the pool for that specific group. This ensures fairness and that diverse voices are represented across the field .”

Ardelyx, which went to an advisory committee in November 2022 with its phosphate absorption inhibitor Xphozah (tenapanor), suggested that sponsors should have a greater role in the selection of OPH speakers. (See also “Dispute settled? Ardelyx’s Tenapanor gets US FDA panel for dialysis patients” – Pink Sheet, Nov 16, 2022.)

The current lottery system allows other groups to get in line before patients, “which seems unfair and may not necessarily serve the goal of best hearing the patient’s voice,” the company’s comments said.

“The lottery system should be changed from a randomized system to a ‘first come, first served’ principle, which will prioritize patients who have participated in relevant clinical trials or have real-world experience related to the impact of treatment options on their quality of life.”

“We encourage the agency to consider allowing sponsors whose products are under review to offer participants with experience with the product, such as clinicians and patients, [to] speech in the open comment period (OPH),” said Ardelyx. “This should be followed by a separate part for other individuals and in that way this allows participants to be properly present in a meaningful way compared to the current OPH process which seems to be much more haphazard.”

A Likert scale for voting

In a recent survey by 3D Communications of current and former adcomm members, 95% of respondents either agreed or strongly agreed that there should be a benefit-risk voting question at meetings where an application seeking approval is discussed . (See also “Current, Former US FDA Adcomm Members’ Reform Idea: Allow Conflicted Experts To Participate” – Pink Sheet, August 13, 2024.)

Speakers at the June listening session also expressed support for preserving the voting process, saying it was important for transparency and accountability. A patient safety advocate who also serves as an adcomm consumer representative suggested a voting method where panelists indicate their confidence in the data on a numerical scale. (See also “Advisory Committees: US FDA Should Explain Divergent Decisions But Keep The Vote” – Pink Sheet, June 19, 2024.)

This proposal found support in some written comments.

Comments from the Milken Institute’s FasterCures team recommended that adcomms continue to use polls to make recommendations to the FDA and to spur further discussion in advisory committees.

But “a recommendation that uses a scaled voting mechanism such as a Likert scale may allow committee members to express the certainty of their recommendations,” FasterCures’ comments said. “This method can replace dichotomous questions, which can be perceived as a decision by the committee members.”

“A recommendation that uses a scaled voting mechanism such as a Likert scale can allow committee members to express the certainty of their recommendations. This method can replace dichotomous questions that can be perceived as a decision by the committee members.” – FasterCures

Genevieve Kanter, an economist and associate professor of public policy at the University of Southern California, also suggested the agency could ask for a separate assessment of the overall benefits and risks, each rated on a scale of one to four.

“Given that ‘FDA approval of a drug means that … the drug is determined to provide benefits that outweigh its known and potential risks,’ these separate benefit and risk assessments would provide the two crucial elements of an approval stance ,” Kanter’s comments state. “In this way, the agency would have useful and nuanced summary measures that provide an approval recommendation but do not exacerbate existing confusion about the role of advisory committees.”

Alternatively, Kanter said the agency could request a detailed final approval recommendation document, which adcomm members must submit in writing within one to two days of the meeting.

Lykos Therapeutics said a final non-binding vote may not be the most efficient way to gather expert advice for the agency’s consideration. “The agency could consider alternative measurement tools, such as a Likert scale, to be used in lieu of a poll to enable committee members to effectively rate the briefing submissions,” the company’s comments said.

In June, Lykos endured a negative adcomm review of its midoamphetamine for post-traumatic stress disorder. (See also “Therapy Component Trips Up Lykos’ MDMA At US FDA AdComm For PTSD” – Pink Sheet, Jun 4, 2024.) The FDA subsequently issued a full response letter recommending the company conduct another Phase III trial of the psychedelic.

Lykos said it plans to raise concerns about the structure and conduct of the adcomm in seeking reconsideration of the CRL. The company pointed to the limited number of subject matter experts in the panel and meeting discussion, which at times went beyond the scientific content of the briefing papers. (See also “US FDA Advisory Committee Conduct Could Take Center Stage in Lykos Appeal of MDMA Rejection” – Pink Sheet, August 12, 2024.)