Woodcock Backs Patient Input, Expanded Sentinel in Next PDUFA
FDA believes proposed recommendations for reauthorizing the Prescription Drug User Fee Act (PDUFA) for fiscal years 2018 through 2022 will provide strong and a comprehensive set of enhancements and refinements to the user fee program. Speaking at a 8/15 user fee pubic meeting, CDER director Janet Woodcock said she sees great opportunities for enhancing the science of patient input into regulatory decision making. She said the proposed PDUFA 6 would “evolve fit-for-purpose tools that will enable patient groups and other stakeholders to collect meaningful patient input on what really matters to them as far as drug therapeutics.” This will help make sure “regulators are applying benefit/risk calculus that really reflects the position of the patients on what the burden of disease means to patients, what relief they are seeking and what different adverse events mean to them,” she said.
Another opportunity under PDUFA 6 would see a significant expansion of the Sentinel safety network and integration of the system into pharmacovigilance activities as a routine partner, according to Woodcock. “This will continue to improve overall drug safety and our understanding of the performance of new drugs once they get out into the market,” she said. “Sentinel is really pointed as a landmark in using electronic health data in a large-scale way, but we need to really institutionalize that and integrate it into our drug safety activities and really learn how in every instance possible we can obtain as much information from electronic health records and claims data as possible to enhance drug safety.”
Sentinel will also be looked at as a core tool for “real world evidence” and how that can be utilized in regulatory decision making, Woodcock said. The question is how to use Sentinel to collect data for use in premarket decisions, particularly those supplemental uses of drugs and in general how drugs are used post-market and their effects, she said.
Recruiting, hiring and retaining the best scientific medical personnel was a recurring theme mentioned by FDA and stakeholders during the meeting. The user fee goals letter proposes to modernize the hiring system and infrastructure, augment human resources capacity through the use of dedicated expert contractors, and establish a dedicated function for the recruiting and retaining scientific staffing. Biotechnology Innovation Organization senior vice president Kay Holcombe noted that if these are not met, then the PDUFA goals cannot be met.
PDUFA 6 also proposes to advance “model-informed drug development” (MIDD) approaches. The success of MIDD has been widely communicated in published literature, according to CDER officials, and it results in trial design enhancements in the form of shorter trials with fewer patients, increased probability of regulatory success, and optimized drug dosing. Under the next PDUFA, the agency plans to convene a series of workshops to identify best practices for MIDD, and conduct a pilot program for MIDD approaches – including dedicated meetings with the sponsor to discuss the development and application of models and simulations (e.g., for disease progression, concentration-response). CDER will also develop guidance, or revise relevant existing guidance, on model-informed drug development and strengthen its staff capacity to support MIDD strategies.
On the meetings front, CDER senior advisor Patrick Frey said the number of formal meeting requests is rapidly increasing and over 3,000 formal PDUFA meeting requests were received from sponsors in 2015. This is very difficult to manage, he said, because meeting background packages can be lengthy (1,000-plus pages), and current timeframes do not allow enough time for review and internal deliberation before providing advice to companies on complex drug development questions. The user fee proposal aims to tweak the meetings by creating a “Type B” meeting request for “end-of-phase” meetings, and it would modify the timing for FDA’s response to meeting requests, submission of meeting packages, and FDA’s issuance of preliminary responses for Type B and C meetings to give the agency more time to review the packages. Frye also said that the next PDUFA would allow FDA and a company to agree on a communication plan during application review of application to possibly exclude a mid-cycle meeting or opt to have monthly teleconferences instead.
National Consumers League health policy director Karin Bolte said her organization is concerned that user fees allow industry to set its own agenda at the agency, and she urged FDA to remain independent and maintain its gold standards for reviewing and approving products. The organization feels more emphasis should be placed on improving FDA’s drug safety system. Bolte said user fees funding should also be directed to examining the safety of off-label prescribing, and requiring pre-approval for all direct-to-consumer ads.
Additionally, National Center for Health Research government relations manager Paul Brown also expressed concern about the proposed PDUFA renewal’s lack of emphasis on improving drug safety. He urged FDA to make Sentinel databases available to independent researchers so they can perform their own assessments of drug safety. And he said PDUFA 6 should provide funding to monitor off-label uses of drugs. “With PDUFA funding, FDA could identify the top drugs prescribed off-label and target them for increased postmarket surveillance,” he said.