ANALYSIS OF FDA REVIEW COMMENTS ON PATIENT-REPORTED OUTCOMES IN NEW DRUG APPLICATIONS(2021-2025)
Author(s)
Aerang Hyeon, BSN1, Kyunghee Kim, MBA1, Hae Sun Suh, MPharm, MA, PhD2;
1Graduate School, Kyung Hee University, Department of Regulatory Science, Seoul, Korea, Republic of, 2College of Pharmacy, Kyung Hee University, Seoul, Korea, Republic of
1Graduate School, Kyung Hee University, Department of Regulatory Science, Seoul, Korea, Republic of, 2College of Pharmacy, Kyung Hee University, Seoul, Korea, Republic of
OBJECTIVES: Patient-Focused Drug Development (PFDD) guidance reflected growing regulatory emphasis on patient-reported outcomes (PROs). This study aimed to characterize FDA PRO evaluation patterns by classifying review comments and identifying associations with labeling outcomes in recently approved drugs (2021-2025).
METHODS: This study applied empirical classification to regulatory review comments. A classification framework comprising 6 main categories and 20 subcategories was developed based on prior research and PFDD guidance series (Guidance 3-4). Using this framework, directed content analysis was conducted on FDA review documents for new drug products approved between 2021 and June 2025 that included at least one PRO as a primary or secondary endpoint supporting the evaluation of efficacy. Two independent reviewers coded PRO-related comments, with each comment serving as the unit of analysis; discrepancies were resolved through consensus meetings. Descriptive statistics analyzed comment frequency by category and distribution according to PRO labeling outcomes.
RESULTS: A total of 539 PRO-related comments were identified from 76 products. The most frequent categories were "Treatment Benefit" (35.3%) and "Statistical Analysis" (23.4%), followed by "Fit-for-Purpose" (17.1%), "Administrative" (11.3%), "Study Design" (7.4%), and "Data Quality" (5.6%). Products achieving PRO labeling (n=34, 43.0%) showed higher proportions of "Treatment Benefit" comments (43.2% vs 24.1%) than those without labeling (n=45). In contrast, products without labeling had more "Study Design" comments (13.8% vs 2.9%). Notably, "Masking and Bias" comments appeared in only one successful product versus 24 unsuccessful products. Among oncology products (n=15), only one achieved PRO labeling, with "Statistical Analysis" comments being most frequent (38.1%).
CONCLUSIONS: This study empirically provided insights into how PFDD principles were applied in FDA review practice. "Study Design" issues, particularly "Masking and Bias," were associated with labeling failure, highlighting the importance of blinded, controlled designs for PRO endpoints in pivotal trials. These findings emphasized aligning PRO strategy development with FDA evaluation patterns to achieve successful labeling.
METHODS: This study applied empirical classification to regulatory review comments. A classification framework comprising 6 main categories and 20 subcategories was developed based on prior research and PFDD guidance series (Guidance 3-4). Using this framework, directed content analysis was conducted on FDA review documents for new drug products approved between 2021 and June 2025 that included at least one PRO as a primary or secondary endpoint supporting the evaluation of efficacy. Two independent reviewers coded PRO-related comments, with each comment serving as the unit of analysis; discrepancies were resolved through consensus meetings. Descriptive statistics analyzed comment frequency by category and distribution according to PRO labeling outcomes.
RESULTS: A total of 539 PRO-related comments were identified from 76 products. The most frequent categories were "Treatment Benefit" (35.3%) and "Statistical Analysis" (23.4%), followed by "Fit-for-Purpose" (17.1%), "Administrative" (11.3%), "Study Design" (7.4%), and "Data Quality" (5.6%). Products achieving PRO labeling (n=34, 43.0%) showed higher proportions of "Treatment Benefit" comments (43.2% vs 24.1%) than those without labeling (n=45). In contrast, products without labeling had more "Study Design" comments (13.8% vs 2.9%). Notably, "Masking and Bias" comments appeared in only one successful product versus 24 unsuccessful products. Among oncology products (n=15), only one achieved PRO labeling, with "Statistical Analysis" comments being most frequent (38.1%).
CONCLUSIONS: This study empirically provided insights into how PFDD principles were applied in FDA review practice. "Study Design" issues, particularly "Masking and Bias," were associated with labeling failure, highlighting the importance of blinded, controlled designs for PRO endpoints in pivotal trials. These findings emphasized aligning PRO strategy development with FDA evaluation patterns to achieve successful labeling.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
HPR19
Topic
Health Policy & Regulatory
Topic Subcategory
Approval & Labeling
Disease
No Additional Disease & Conditions/Specialized Treatment Areas