By Nadine Bouchard (VP, Regulatory Affairs, Head of Program Management) and Lisa Sanders, PhD (Sr. Director, Regulatory Affairs)
Background
To help in their decision-making, the US Food and Drug Administration (FDA) sometimes makes use of an Advisory Committee, as defined in various regulations. An Advisory Committee provides independent expert advice and makes non-binding recommendations to the FDA review divisions. There are approximately 45 to 50 standing committees, among which the Oncology Drugs Advisory Committee (ODAC) is one of the most active. The ODAC reviews and evaluates data concerning the safety and effectiveness of human drug products for use in the treatment of cancer.
Companies view the ODAC meeting as a make-or-break for their product’s approval, and it is true that more often than not the FDA follows the ODAC vote. So, a successful ODAC meeting is paramount, and keeping tabs on news and developments related to the ODAC is an important part of the planning process.
ODAC Activity and FDA "Conversations on Cancer” Session Highlights
The ODAC has already had a busy 2024, with 4 meetings conducted or scheduled through the end of May with 2 of those meetings to discuss pending applications for market approval. For comparison, ODAC met 7 times in 2023 (5 discussions of pending applications) and 5 times in 2022 (4 discussions of pending applications).
In a recent FDA Conversations on Cancer session, ODAC Chronicles – Past, Present, & Future of Oncology Advisory Committees, Dr. Richard Pazdur, the director of the FDA’s Oncology Center of Excellence (OCE), discussed several topics of particular interest:
- A return to in-person ODAC meetings during 2024
- His strong preference for a point/counterpoint style briefing book for the ODAC members
- The need for a vote of the ODAC and whether meetings could be comprised of discussion only
Returning to Face-to-Face
The return to the face-to-face format is a welcome change; since March 2020, all ODAC meetings have been conducted virtually. ODAC meetings conducted in a virtual format do not recapitulate the level of interaction and discussion that were typical in the face-to-face format. Though a video interface is used, the video feed is limited to the individual speaking. ODAC members attend remotely, separated from each other and from the FDA and Applicant attendees. Though ODAC meetings have always been formal affairs, the virtual format made it feel more so. The virtual format requires a high degree of technical control on the FDA’s side, and though the FDA ODAC technical support team is proactive and collaborative, the need to control presentation access can lead to lags in the discussion, particularly when the Applicant is responding to questions. Being recognized by the ODAC chair to make a counter response and gaining access to supporting slides takes time that can stymie discussion. The open public hearing portion of the meeting, which is important, can be negatively impacted by technical glitches affecting the ability of the ODAC to hear from patient advocates and other interested parties, who lack the sophisticated technical support available to the FDA and Applicants.
Point/Counterpoint Briefing Document Format
During the ODAC discussion, both Dr. Pazdur and some ODAC attendees expressed their preference for the point/counterpoint briefing document format, proposed under Project Point/Counterpoint in 2019. This recommended format is intended to combine the Applicant’s and FDA’s briefing materials into a single, concise document not to exceed 35 pages (including tables and figures).
The combined FDA and Applicant ODAC briefing document is intended as a stand-alone document (i.e., the information and supportive evidence provided should be self-sufficient) that contains:
- A single background information section
- Objective descriptions of the data for the subject under discussion at ODAC
- The position of the Applicant and the FDA
The OCE feels the combined format increases the transparency of differences in viewpoints and is more concise to focus on salient data and facilitate the committee’s understanding of the critical issues for discussion.
Traditional vs. Point/Counterpoint Format
The traditional approach to the ODAC briefing materials sees the FDA and the Applicant preparing separate documents, with the Applicant’s version generally due to the FDA about 2 weeks prior to the FDA due date for their briefing materials. For the combined point/counterpoint briefing document, the Applicant portion is submitted 3 to 5 weeks sooner than the traditional briefing document. In either scenario, the Applicant provides their materials to the FDA prior to the FDA finalizing their briefing materials. For the point/counterpoint format, the Applicant provides no input into the FDA portion, and cannot edit their portion after submission. The FDA cannot edit the Applicant’s content. The FDA ensures the compiled briefing materials are provided to the ODAC and released into the public domain prior to the ODAC meeting via posting on the ODAC meeting website. Among the FDA advisory committees, only the ODAC is currently asking Applicants to contribute to a joint point/counterpoint document.
Benefits and Challenges of the Point/Counterpoint Format
There was a clear preference for the combined format from the OCE and at least some ODAC members. For the ODAC members, receiving the Applicant’s and FDA’s briefing materials in a single document provides a structured presentation of each party’s interpretation of the data, an approach particularly helpful where the perspective of the FDA and the Applicant are not aligned. Not having to flip between two documents to compare the FDA’s and Applicant’s positions allows the ODAC members to prepare for meetings more easily and to fully understand differing positions between the FDA and Applicant.
For the Applicant, preparation of the presentation slides and ODAC briefing materials comprises a significant share of ODAC preparations, and anyone who has been involved in ODAC preparations knows the challenge to creating a focused briefing document; there is always a desire to add a bit more information. Applicant’s preparations for an ODAC meeting are generally done in concert with a communication vendor specializing in the advisory committee preparation and are very time- and resource-intensive for the Applicant. The point/counterpoint format’s page limit recommendation forces a concise, targeted presentation of the data supporting the Applicant’s position. Having the briefing document off the To-Do list sooner can allow the Applicant’s team to focus on other preparation activities, such as finalization of slide decks and scripts.
There are times, though, when the shortened timelines may not work in the Applicant’s favor. If an application is under Priority Review, for example, the Applicant’s ODAC preparation timelines are compressed. It may not be feasible to meet the earlier due date for the point/counterpoint format and provide a well-considered presentation of key data that support the Applicant’s position. In our experience, in the Priority Review scenario a few extra weeks are valuable for an Applicant to ensure their ODAC briefing materials are carefully prepared and reviewed to ensure all data are accurately presented. There may also be situations where the point/counterpoint format’s size limitation could pose a barrier to providing the ODAC with adequate information supporting the Applicant’s position on questions raised by the FDA review team. For small to mid-sized companies that lack expensive resources to support ODAC preparation, extra weeks can also be vital.
Responding to a Request for a Joint Briefing Document
So, how should the Applicant respond to a request for a joint briefing document for their ODAC? Are they required to comply? In short, no; use of the combined document is not currently a requirement. As stated on FDA’s Project Point/Counterpoint webpage, “applicants are offered the opportunity to use the combined briefing document in lieu of a traditional briefing document.” When approval of an application is on the line, an Applicant must evaluate the situation carefully and determine if their preparation timelines can accommodate the earlier submission of their briefing materials to the FDA. The Applicant should assess if they feel the point/counterpoint presentation of their data, one in which they may be in direct conflict with the FDA’s data presentation, will serve their needs with regards to informing the ODAC’s discussion and vote.
In a situation where FDA is not asking the ODAC to weigh in on the approval of an application, as seen in a Combined FDA and Applicants ODAC Briefing Document example in a recent ODAC discussion of the appropriateness of the minimal residual disease (MRD) as a surrogate endpoint in multiple myeloma, the reservations for using the joint briefing document are largely absent.
Advisory Committee Voting
Advisory committee meetings typically conclude with a vote by the committee on a single voting question posed by the FDA. More often than not, the FDA’s approval decision follows the committee vote, and there is concern that this can give an appearance that the committee is making a regulatory decision. This appearance led to FDA Commissioner Robert Califf pushing for fewer votes, feeling that what the FDA review team wants most is the thinking behind the vote. In contrast, Richard Pazdur and the majority of the former and current ODAC members taking part in the ODAC discussion appeared to favor continuing the committee vote.
If an advisory meeting lacks a vote, the conclusion of the committee as a whole may be difficult to interpret. A positive vote by the committee is an important milestone for the Applicant in the application review process, and it provides the FDA with both a succinct conclusion from the committee and the strength of that conclusion (indicated by the number of “yes” and “no” votes).
Upcoming Listening Session on Advisory Committee Meetings
Of note, FDA has a listening session planned for 13 June 2024, Optimizing the Food and Drug Administration’s Use of and Processes for Advisory Committees; Public Meeting. The purpose of the listening session is to discuss the Agency’s use of and processes for its advisory committee system, more specifically in three general areas:
- Composition of advisory committees
- Service on an advisory committee as a Special Government Employee (SGE)
- Public perception and understanding of advisory committees
Closing Remarks
In summary, the ODAC’s return to in-person meetings and the preference for a point/counterpoint briefing format reflect ongoing efforts to enhance the effectiveness and transparency of advisory committee deliberations. While these changes offer significant benefits, they also pose challenges that Applicants must carefully navigate. As the FDA continues to refine its advisory committee processes, staying informed and adaptable will be crucial for all stakeholders involved.
Our regulatory and clinical strategy experts at Allucent, comprised of previous senior leaders at the FDA and other regulatory authorities, can guide you through these complex regulatory hurdles providing cost-effective and scalable, tailored solutions for your specific needs.
If you are interested in hearing more about regulatory topics within oncology drug development, check out this new podcast on the topic of Radiopharmaceuticals. Podcast: Advancing Oncology Research: Regulatory & Development Path for ADCs & RDCs
You may also be interested in reading this blog on the effective use of single-arm trials for oncology. Advancing Oncology Drug Development: The Importance of Single-Arm Trials