Presentation (CTI)

OBJECTIVES: Using patient reported outcome (PRO) measures to assess severity and frequency of adverse events (AEs) in oncology clinical trials has been previously described but approaches to instrument/ item selection vary and best practice guidelines to support these activities are limited. This study reviewed guidance documents and publications to identify approaches for selecting instruments/items measuring patient-reported tolerability across oncology trials.
METHODS: A targeted search of publications and guidelines was conducted. Search platforms included PubMed, regulatory websites (EMA/FDA), Industry websites (ISPOR/ISOQOL) and therapeutic conferences. Search terms included ‘tolerability’, ‘adverse event’, ‘side effects’, ‘patient reported’, and ‘patient reported-outcome common terminology criteria for adverse events (PRO-CTCAE)’.
RESULTS: PRO-CTCAE items were most commonly used to collect patient-reported AE data, with other PRO measures to assess overall AE burden, physical functioning and drug-specific AEs not included in the PRO-CTCAE. Methods used to select PRO-CTCAE items varied, including literature reviews, clinician interviews and consensus, patient input and COA expert review. Several studies employed a combination of selection methods. Disease specific item sets were identified for multiple myeloma, prostate, breast, ovarian and rectal cancer, and for groups including adolescents, phase 1 trials, and for specific treatment classes. The FDA Guidance notes that a core set of PRO measures should be selected at a minimum to capture the patient experience in cancer trials; examples of instruments/items are provided including the EORTC QLQ-C30 and FACIT item library in addition to the PRO-CTCAE. Definitive guidance on selecting instruments/items is lacking. The EMA has limited guidance on selecting specific instruments for collecting such data, but suggest further experience of using the PRO-CTCAE is required.
CONCLUSIONS: The PRO-CTCAE was widely used to assess patient reported AEs. Variation in methods used to select PRO-CTCAE items was found, including examples with no patient input. However, information as to how sponsors should practically select items was sparse.