P120: Clinical Outcome Assessment (COA) Qualification Program Analysis
Poster Presenter
Felix Yang
US Regulatory Policy Fellow
Genentech, A Member of the Roche Group United States
Objectives
To perform data analysis on the types and the average review timeline of COAs that have gone through the qualification program, as well as the utilization of qualified COAs in drug clinical trials.
Method
The submission and review dates for LOI, QP, and FQP steps were retrieved from CDER & CBER’s database, as well as the FDA COA Qualification Program website. We analyzed the Summary Basis of Approvals retrieved from Drugs@FDA and the COA compendium to assess the use of qualified COAs.
Results
Out of the 79 COA submissions currently listed in the qualification program, a majority of them (60.8%) are Patient Reported Outcomes (PRO), followed by Performance Outcome Assessments (11.4%), DHT-Passive Monitoring (10.1%), and others. On average, total time spent in the qualification program for submissions are 6.93 years and 4.92 years for submissions entered prior to and post 21st Century Cures Act respectively. Per FDA DDT guidance, Letter of Intent (LOI), Qualification Plan (QP), and Full Qualification Package (FQP) review timelines are 3 months, 6 months, and 10 months respectively with a completeness assessment (CA) prior to review. For CA’s, on average, it takes 26 days for LOI CA review, 76 days for QP CA review, and 4 days for FQP CA review. For submission review, on average, it takes about 3.57 months for LOI review, 9.00 months for QP review, and 14 months for FQP review. The maximum time it took to review submissions for LOI, QP, and FQP are 11.43 months, 23.47 months, and 23.27 months respectively. The minimum time it took to review submissions for LOI, QP, and FQP are 1.73 months, 2.00 months, and 8.93 months respectively. As of today, 7 COAs have been qualified with 3 of those used to support drug clinical trials. All of which are PRO’s. KCCQ, qualified in 2020, was used in 10 clinical trials from 2003 to 2023 and cited as exploratory endpoint 5 times and secondary endpoint 5 times. E-RS: COPD, qualified in 2016, was used as an exploratory endpoint in 2019. EXACT, qualified in 2014, was used as an exploratory endpoint in 2 clinical trials (2017 and 2019), and as a secondary endpoint in 2020.
Conclusion
This analysis sought to investigate review timelines for COAs that are submitted to the qualification program. When compared against the proposed timeline from FDA DDT guidance, submissions are equally split between being reviewed on time versus delayed across the LOI, QP, and FQP stages. For the CA portion of the review, there is a wide range of CA timelines across the 79 submissions in the program currently. The lack of a clear review timeline makes it complicated to predict the overall review time for each stage of the submission and the overall time it takes for a COA to be qualified. It is difficult to predict the overall impact of the “qualified” status of a COA, on its subsequent use as a key endpoint in drug clinical trials. All 7 qualified COAs were qualified as a “measure”, stated in the qualification determination, all requiring “additional development work to further assess measurement properties”. While 3 of the 7 qualified COAs were used to support drug development, their role in the approval were limited as mostly exploratory and secondary endpoints and in some situations, as key secondary endpoints. No qualified COA was able to support drug clinical trials as a primary endpoint. Overall, it is difficult for Drug Development Programs to plan for qualification for a COA due to uncertain review timelines and narrow use of qualified COAs in drug clinical trials to support approvals.
