Over the years, we have written about the FDA’s Advisory Committees with a special interest on “conflict of interest” issues. Recently, Avalere researchers published an interesting look at FDA’s Advisory Committees (AdComm), considering trends in the first three years of current user fees. The study aimed to provide insight into developments regarding FDA’s approach to the AdComm process. The research is based on data from programs related to the FDA Safety and Innovation Act. The follow information can be found in the Avalere report.
Advisory Committees
The Food and Drug Administration Amendments Act (FDAAA) of 2007 requires FDA to hold Advisory Committee meetings for the approval of all new molecular entities. The researchers point out that the process surrounding AdComms “remains a source of significant uncertainty for biopharmaceutical and medical device product sponsors.” Mandatory meetings are required in the review of pediatric adverse events or labeling changes, biannual Drug Safety and Risk Management committee meetings on postmarket safety, and device classification/reclassification.
AdComms are comprised of members that are appointed by the FDA Commissioner based on their scientific or technical expertise, and supplemented by other experts as needed. FDA has 34 standing AdComms and although the agency is not required to follow the advice of the AdComms, it generally does when evaluating product approvals. The researchers point out that “of the 214 AdComms convened to discuss product approvals between 2008 and 2012, panelists voted to approve a product 74% of the time, and FDA ultimately approved the corresponding product 79% of the time.”
Findings
The researchers analyzed publicly available AdComm data between FDA fiscal year (FY) 2013 and FY 2015. During this time, FDA held 222 AdComm meetings, with the majority taking place within FDA’s Center for Drug Evaluation and Research (CDER), the Centers for Biologics Evaluation and Research (CBER), and the Center for Device and Radiological Health (CDRH). They comprised 82% of the meetings. 57% of their meetings were held to discuss approvability of a sponsor’s product application.
Additionally, since FY 2013, the number of AdComms held to decide approvability of new or supplemental New Drug Applications (NDAs) has decreased, while Premarket Approvals (PMAs) increased, especially in FY 2014. The direct approval recommendation rate for these meetings was 73% which is similar to those seen in previous user fee authorizations. The researchers note that “approvability questions posed in alternative forms (e.g., regarding safety and effectiveness) resulted in favorable votes 92% of the time.”
The research also indicates that some AdComms may be more challenging than others in terms of receiving a positive recommendation. For example, the Cardiovascular and Renal Drugs AdComm under CDER has met to discuss product approvals 10 times since FDASIA, with a product approvability recommendation rate of 50%. FDA has followed the Committee’s recommendations over 80 percent of the time. Alternatively, the Oncologic Drugs AdComm, which met seven times to discuss approval of 11 products, voted in favor of approval less than one third of the time. Interestingly, the research points out that FDA ultimately approved about 64% of those products.
Furthermore, each committee meeting appears to be different, depending on the product being reviewed, comments stated during the public comment period, and the makeup of the panel. The researchers note that this does not mean AdComms are influenced in unpredictable ways. Rather, most “demonstrate similar influences when considering the evidence at hand,” citing a survey that found 74% of AdComm members read the entirety of the sponsor briefing book prior to a meeting, while 60% spend equal time on sponsor and FDA-prepared materials. Government-produced content is indicated as being more influential on the members, and the meeting itself appears to have at least some influence on their voting behavior.
Report’s Meaning
As pointed out by the researchers, AdComms are often “make or break” moments in the effort to secure an FDA drug, biologic, or device approval. Significant resources are put into these meetings, so this research will be useful to many life science companies. Approval rates vary, between 29 to 88 percent, but the Cardiovascular and Renal Drugs Committee appears to be one of the strictest. The researchers note “given the greater emphasis placed on the patient voice and patient-focused drug development, product sponsors should keep in mind that AdComms are venues that allow patients to weigh in on the benefit/risk profile of new products. As such, public comments will likely increase, rather than decrease, in importance in the future.”
Additionally, although it is rare where the FDA does not follow the recommendation of an AdComm, the agency occasionally approves drugs that AdComms recommended against. In one case, the research notes an ovarian cancer drug of which an AdComm voted to delay approval, yet ultimately FDA accelerated approval of the drug on the condition that the sponsor successfully demonstrate positive results in Phase III trials. Additionally, for biosimilars, FDA has said it will hold AdComms to discuss “at least the first biosimilar to any given reference product.”
The researchers conclude that the AdComm process is one undergoing an evolution. It cites the FDA’s decision to create a Patient Engagement AdComm to offer advice to FDA on the patient perspective into clinical trials, labeling, and risk-benefit analyses. FDA may choose to develop more, especially as priorities change and there becomes additional improvements and understanding in the regulatory science space.