Patient-Focused Drug Development, Complex Trial Design May Not Get More Funding In PDUFA VII
Executive Summary
US FDA proposed increasing staffing and resources for both programs during the next user fee program cycle, but industry representatives did not believe it necessary.
Drug sponsors balked at increasing user fee funding for the Patient-Focused Drug Development and Complex Innovative trial Design programs, questioning the additional staff proposed to maintain and expand them.
Members of the prescription drug user fee reauthorization negotiating teams are finalizing language for the commitment letter that would extend the program another five years. (Also see "PDUFA Renewal Negotiations Nearly Complete, With CBER Slated For Major Resource Increase" - Pink Sheet, 18 Feb, 2021.) Among the issues debated by industry and US Food and Drug Administration representatives during a series of December 2020 Regulatory Decision Tools subgroup meetings were improvements to the Patient-Focused Drug Development (PFDD) program.
The FDA proposed using PDUFA VII funds to pay for an expanded grants program to develop publicly-available standard core sets of clinical outcome assessments (COAs). Industry officials did not like the idea of user fee funds paying for “third party” studies or grants and did not agree to funding the work, according to minutes of the 1 December meeting.
“Industry suggested that FDA consider the development of guidance on patient preference studies in regulatory decision making,” according to the minutes.
Industry gave another counteroffer during an 8 December subgroup meeting, suggesting “a potential willingness to support some of the program staffing that would be needed to administer and manage such grants or contracts.”
But the FDA said that staffing would be dependent on “the level of program activity, which in turn will be a function of projected future availability of non-user fee funds for this purpose,” according to the 8 December meeting minutes.
Non-user fee funding commitments for the project were unknown, leaving the idea’s future in doubt. During a 15 December meeting, the most recent update available, the FDA had not determined whether non-user fee funding could support the COA grants program.
Both sides considered “how the scope of the proposal would change with changed resources,” according to the 15 December meeting minutes.
More COA Grant Applications Under Consideration
A core clinical outcome set pilot grant program was created as part of the PFDD program in 2019 to support development of COAs and related endpoints for specific diseases. The agency committed $4.2m to fund up to three proposals in fiscal year 2019. (Also see "Clinical Outcome Assessments To Be Developed Under US FDA Grants" - Pink Sheet, 18 Sep, 2019.)
Applications for the next round of grants are under review, according to the FDA website. The agency will fund another up to three grants totaling $4.2m in grants in FY 2021.
COAs can offer a standardized set of measures in a particular disease, which could help streamline clinical trials and drug development. (Also see "US FDA Mulling Core Criteria For Patient-Reported Outcomes" - Pink Sheet, 1 Nov, 2018.)
The PFDD program is intended to increase the patient voice in FDA decision-making. The FDA held many disease-focused meetings for patients and advocates to offer their opinions on unmet needs and treatment preferences. Views were published in reports that FDA assessors could consult when making approval decisions. The program also spawned similar meetings run by outside groups and attended by FDA officials. (Also see "Patient-Focused Drug Development: US FDA’s Guidance Development Effort Passes The Mid-Point" - Pink Sheet, 9 Feb, 2020.)
Some reports from those meetings became disease-specific development guidances. (Also see "Duchenne Muscular Dystrophy: FDA Supports Broader Outcome Measures, Biomarkers" - Pink Sheet, 10 Jun, 2015.)
CID Program Needs More Funding, Industry Raises Questions
Industry also questioned the additional funding requested for the Complex Innovative trial Designs (CID) program, which allows sponsors opportunities to discuss alternative designs with FDA staff.
The FDA said that more resources would be necessary to continue the program and issue additional guidance. Industry representatives said during the 1 December meeting that while they would like the CID program to continue, they “wanted to consider a continuation with fewer enhancements than were being proposed by FDA to limit the amount of additional resourcing that would be required to support a continuation,” according to the minutes.
The FDA offered two alternative proposals that would require fewer resources. During an 8 December subgroup meeting, industry representatives stated that they wanted to maintain several aspects of the program, but with fewer staff than the agency said was necessary.
Industry questioned whether the resources FDA wanted were necessary in part because the Center for Biologics Evaluation and Research had not met with any sponsors through the CID meeting process. CBER reported they had reviewed several proposals and held several “CID consultations,” but using the traditional formal meeting route, according to the minutes.
FDA officials said during the 15 December meeting that no agreement was possible with the reduced staffing level industry representatives proposed. More discussions were expected at future meetings.
120-Day Requirement Between CID Meetings May Be Dropped
CID program participants now are offered two meetings with agency staff 120 days apart to discuss details of their trial designs. FDA and industry decided to remove the requirement for PDUFA VII because they found the “stipulation limited desired flexibility,” according to the 15 December meeting minutes.
Industry still said a “nominal timeframe” between meetings would be helpful “to provide an indication to sponsors of the time frame to be expected.” The FDA said it would determine an optimal meeting window.
The CID program suffered some headaches at launch, including questions about whether sponsors would participate. While many were interested in discussing innovative trial designs with the FDA, some were not enthusiastic about the agency disclosing them publicly, a requirement of participation. The agency set a policy limiting the information that would be released. (Also see "Complex Innovative Designs Pilot Likely Satisfies Industry's Disclosure Worries" - Pink Sheet, 29 Aug, 2018.)
FDA officials began publicly discussing CID case studies and lessons learned in 2020. (Also see "US FDA, Industry Share Early Lessons From Complex Innovative Trial Designs Program" - Pink Sheet, 29 Jun, 2020.)