Presentation (CTI)

OBJECTIVES: To evaluate sources of PICO divergence and their implications for evidence generation, including insights from the first published JCA of tovorafenib.
METHODS: A targeted review of EU HTA guidance, peer-reviewed publications, and publicly available JCA analyses was conducted. Data were extracted on PICO development, consolidation, sources of divergence, and evidence-generation implications. Findings were supplemented with a case study of the first published JCA report for tovorafenib.
RESULTS: Twenty-nine records were identified, 25 underwent full-text review, and 18 were included. Comparator selection consistently emerged as the primary driver of PICO divergence. Published analyses of 35 PICO exercises across 20 indications reported an average of eight consolidated PICOs from seven participating countries, while an oncology simulation generated 67 PICOs across 25 countries. The first published JCA (tovorafenib) defined eight PICOs across three patient populations; however, comparative evidence was included for one PICO. Comparator data were unavailable for six PICOs, while one additional comparison was excluded because of insufficient information. Consequently, only one of eight scoped PICOs (12.5%) informed the final comparative assessment.
CONCLUSIONS: Early JCA experience indicates that comparator heterogeneity is a key driver of PICO divergence and evidence-generation burden. Although PICO consolidation aims to harmonize evidence requirements, the tovorafenib assessment shows that the number of retained PICOs may exceed available comparative evidence. Greater transparency in PICO consolidation and clearer methodological guidance may improve the feasibility and predictability of future JCA submissions.