OBJECTIVES: Pediatric patient-reported outcome (PRO) data can complement existing safety and efficacy data by quantifying symptom and functional outcomes from the patient’s perspective. This information can help inform FDA’s benefit-risk assessment of cancer therapeutics. This study assessed use of PROs in pediatric oncology registrational trials submitted for FDA review.

METHODS: FDA databases were searched to identify pediatric oncology product applications approved between November 1997 and April 2020. Sponsor-submitted documents were reviewed to determine whether PRO data were collected, which instruments were used, and the quality of collected data (sample size, attrition, completion rates, use of fit-for-purpose instruments, and thresholds for clinically meaningful within-patient change). The role of PROs in each trial (endpoint hierarchy) was also recorded, along with whether any PRO endpoints were included in product labeling.

RESULTS: Seventeen pediatric oncology applications were reviewed, 4 included PRO data: Denosumab, Tisagenlecleucel, Larotrectinib, and Selumetinib. In these 4 instances, PROs served as exploratory endpoints and were not incorporated in product labeling. The Pediatric Quality of Life Inventory ^TM (PedsQL) Generic Core Scale was the most widely used instrument. Trials collecting PRO data were single-arm studies with sample sizes ranging from 28 to 88 patients. Only 1 of the 4 trials reported PRO assessment completion rates. Symptomatic Adverse Events (AEs) were predominately characterized using clinician-reported Common Terminology Criteria for Adverse Events (CTCAE) without additional patient-report.

CONCLUSION: PROs were infrequently utilized in pediatric cancer registration trials. When used, PRO data were often limited by lack of a clear prospective statistical analysis plan, high levels of missing data, and use of instruments that were not fit-for-purpose. Contemporary PRO symptom libraries such as the National Cancer Institute’s Pediatric PRO-CTCAE may provide an opportunity to better evaluate the occurrence and impact of symptomatic AEs and complement standard clinician-reported safety data in pediatric oncology trials.