Do Public Hearing Participants Influence Outcomes of FDA Advisory Committee Meetings?
Originally appeared in Regulatory Focus in September 2015. This article discusses the importance of the open public hearing portion of an FDA Advisory Committee meeting.
Many regulatory changes have impacted the US Food and Drug Administration approval process for new drugs and medical devices, including the requirement from the Food and Drug Administration Amendments Act for an Advisory Committee review. Advisory Committees provide the agency with advice from outside experts on issues related to drugs, biological products, medical devices and food. During an Advisory Committee meeting, an independent panel evaluates the benefits and risks of the product. FDA poses one or more questions, including whether the product should be approved, to the panel, and the meeting culminates with a vote on each question.
An important component of the Advisory Committee meeting is the open public hearing (OPH), normally a one-hour session reserved for the public to share opinions about and experiences with the product. The OPH can last as long as, or longer than, the sponsor or FDA presentations during an Advisory Committee meeting, yet there is little research on any potential impact it may have on the voting.
This article summarizes results from a review of Advisory Committee meetings for new drugs and devices between 2007 and 2014, and assesses the potential association between the majority opinion expressed during the OPH and the committee votes. Findings show that the odds of a committee voting in favor of approval are 11.3 times higher when committee members are exposed to a positive OPH than a negative OPH (p=0.001):
This report suggests that a positive OPH is strongly associated with a committee voting in favor of approval.
A Short Synopsis of Advisory Committees
FDA began convening Advisory Committees in the 1960s to evaluate drugs and then, in the 1970s, to review biologics and devices. However, Advisory Committee meetings became mandatory for all new biomedical products in 2007 with the passage of the Food and Drug Administration Amendments Act. It also is important to note that FDA typically follows the recommendations of Advisory Committees regarding approval. Accordingly, Advisory Committee meetings have grown in importance in sponsors’ development planning process.
In a typical one-day Advisory Committee meeting, the sponsor and FDA deliver their presentations to the committee, each of which is followed by a brief question-and-answer period. These presentations are followed by the OPH, in which the general public, advocacy groups, patients, physicians and other healthcare stakeholders are invited to deliver their personal comments to the committee members. Comments made during the OPH often reflect the public’s concerns regarding safety and can raise issues that committee members may then refer to in their deliberations. Alternatively, these comments can provide patient-centric arguments about the need for approval, particularly in cases where the drug being reviewed fills a critical unmet medical need.
Importance of the Open Public Hearing
To date, only two publications reference the importance of the OPH in influencing Advisory Committee members’ voting. In 2012, 3D Communications conducted a survey of more than 2,000 current and former Advisory Committee members to better understand what influences their votes. Approximately 77% of survey responders reported that the comments made during the OPH could influence their vote in some way. In a follow-up survey by 3D Communications published in 2015, that figure remained similar at 81%.
Data for this review were collected from public transcripts of Advisory Committee meetings, which are posted on FDA’s website. Transcripts were limited to meetings for new drugs and devices that took place between 2007 and 2014. Meetings about biologics or vaccines, applications for new indications or label revisions for drugs or devices and policy changes, and those that did not involve a new product, were excluded.
The time period coincides with the FDA Amendments Act of 2007, as well as the last two renewals of the Prescription Drug User Fee Act (PDUFA). Limiting meeting transcripts to this time period minimizes any confounding effects that may have occurred with changes in the regulatory approval process.
The transcripts of Advisory Committee meetings were analyzed to capture the following descriptive data:
- product name and indication
- meeting date and committee(s) present
- total number of participants in the OPH
- numbers of OPH participants who supported or opposed approval
- outcome of the committee’s main benefit-risk vote
The OPH was considered “positive” if more than 50% of the speakers supported approval, “neutral” if 50% supported approval and “negative” if less than 50% supported approval. Each speaker was given equal weight in determining the overall tone of the OPH.
The methodology used in this review simplified the complexity of Advisory Committee meetings and did not factor in all variables that may play a part in the outcome of the meeting.
In total, 243 meetings met the inclusion criteria. Of those, 193 (79%) had an OPH with participants. Importantly, meetings with an active OPH increased during the timeframe analyzed, from 50% in 2007 to 94% in 2014 (Table 2). Complete names and number of meetings for each Advisory Committee can be found in the sidebar.
Table 3 summarizes the frequency of positive, neutral and negative outcomes for all Advisory Committee meetings in the data set with an OPH. Overall, 71% of the meetings resulted in a vote for approval. The percentage of Advisory Committee votes for approval was higher for meetings with a positive OPH (79%) compared to meetings with either a neutral (55%) or a negative OPH (50%).
Table 4 summarizes the results of the logistic regression analysis. The odds that a committee would vote for an approval were 3.7 times higher when exposed to a positive OPH than a negative OPH (p=0.009). The odds of a committee vote for approval were not significantly different between exposure to a negative OPH and a neutral OPH (p=0.70).
Of the 193 meetings included in this analysis, 28 were held by the Oncologic Drugs Advisory Committee (ODAC), 23 by the Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC), 18 by the Circulatory System Devices Panel (CSDP) and 16 by the Cardiovascular and Renal Drugs Advisory Committee (CRDAC). These four committees account for nearly half (44%) of meetings reviewed. Table 5 summarizes meeting outcomes (for or against approval) for each of these four Advisory Committees and are organized by whether the OPH was positive, neutral or negative.
In these four Advisory Committees, the members voted for approval of the product 72% of the time, regardless of the tone of the OPH. When the OPH was positive, the committee voted for approval 81% of the time, and when the OPH was negative, the committee opposed approval 73% of the time. The odds of approval were 11.3 times higher when the committee was exposed to a positive OPH than a negative OPH (p=0.001; Table 6).
Recommendations for Sponsors
In its 2013 draft PDUFA V implementation plan, Structured Approach to Benefit-Risk Assessment in Drug Regulatory Decision-Making, FDA acknowledges that its framework for benefit-risk assessment greatly benefits from the unique and valuable perspectives patients provide. As FDA continues its efforts to incorporate patient perspectives through its PDUFA V patient-focused drug development initiative workshops, the agency’s push for patient participation, and the impact of that participation, are expected to grow, as reflected in the Advisory Committee meetings reviewed in this report. While only half of the meetings in 2007 had an OPH with at least one participant, nearly all meetings in 2014 had an active OPH. And, among the four Advisory Committees that met most frequently, the association between a positive OPH and a vote for approval (OR=11.3) was stronger than for all committees combined (OR=3.7).
Sponsors should consider building awareness of opportunities like Advisory Committee meeting OPHs into their ongoing relations with medical societies, patient organizations, physicians and other healthcare professionals. When these groups contribute real-life examples in the clinical setting and patients’ day-to-day experiences, their perspectives can provide context for the safety and effectiveness evidence submitted by a sponsor, the severity and impact of a condition and the limitations of current standards of care. As reflected in the findings of this report, Advisory Committees are receptive to these perspectives as they evaluate the benefit-risk framework of products under review.
ABOUT THE AUTHOR
Natalie Vargas, MPH, MBA, is a consultant and writer who has helped dozens of clients prepare for FDA Advisory Committee meetings for drugs, devices and biologics across all therapeutic areas. Natalie is a Senior Project Manager at 3D Communications where she uses her expertise to help clients translate complex scientific issues into simple messages. In her role, Natalie reviews clinical trial data, crafts messages, and helps to create FDA deliverables. Connect with her on LinkedIn.