Presentation (CTI)

OBJECTIVES: Patient-reported outcomes (PRO) capture effects that are important to patients and play a central role in incorporating patients’ opinions into regulatory decision-making. We assessed letters of violation related to patient-reported outcomes released by the FDA Center for Drug Evaluation and Research (CDER).
METHODS: We conducted a retrospective descriptive analysis of PRO-related warning and untitled letters (violations that do not reach the warning letter threshold) released by CDER in 1997-2025 and collected from the FDA website. The FDA classifies PRO as marketing and advertising (M&A) activities. We classified the letters by class, media, and type of violation.
RESULTS: CDER released 1,036 letters citing M&A regulation violations from 1997 to 2025, of which 76 (7.3%) were related to PRO. The annual average ± standard deviation of PRO letters declined from 6.3±0.6 in 1997-1999 to 1.2±2.4 in 2020-2025. Most of the letters were for antineoplastic and immunomodulating agents (23, 30.3%). There were 16 (21.1%) letters related to unapproved/investigational drugs. There were 27 (35.5%) letters referring to direct-to-consumer advertising, including 9 (11.8%) television commercials. Six of the letters related to television commercials were released in 2025. The letters contained 82 PRO claims, of which quality of life accounted for 59 (72.0%) claims, patient preference for 16 (19.5%), and patient-reported outcomes related to efficacy for 7 (8.5%). A total of 51 (62.2%) PRO claims were not supported by evidence, 25 (30.5%) used no adequate and well-controlled studies, and 6 (7.3%) had misleading reporting of results.
CONCLUSIONS: Letters citing PRO violations issued by CDER decreased during 1997-2024 and increased in 2025, largely due to letters targeting television M&A. The most frequent PRO violations involved misleading/false claims related to quality of life. Most often, PRO claims were not supported by evidence or adequate and well-controlled studies.