Presentation (CTI)

OBJECTIVES: The introduction of the EU Health Technology Assessment Regulation (HTAR) and Joint Clinical Assessment (JCA) has increased the need for early PICO (Population, Intervention, Comparator, Outcome) prediction and evidence planning. However, predicting future PICO requirements remains challenging in emerging or rapidly evolving therapy areas, e.g., gene and cell therapies, obesity, cardiometabolic diseases, as current treatment guidelines and historical HTA precedents may not reflect future standards of care and comparator relevance. This challenge is further amplified by a paucity of HTA precedents.
METHODS: The validated IQVIA PICO simulation framework was extended by incorporating analyses of pivotal trial designs of analogue assets to generate forward-looking PICO expectations. Key trial characteristics were systematically analysed across recent and ongoing studies, including population definitions, treatment positioning, background therapy, comparator selection, and outcomes. These insights identified emerging patterns and anticipated future PICO requirements not yet reflected in current guidance.
RESULTS: Analysis of pivotal trial designs in obesity and cardiometabolic diseases revealed early signals of evolving standards of care not reflected in current clinical guidelines or HTA decisions. Key findings included a shift towards more clearly defined subpopulations, driven by evolving patient stratification. Treatment positioning is becoming more differentiated across treatment lines; alongside rising expectations for head-to-head evidence against active comparators and a more complex comparator landscape. Outcomes analysis further indicates a shift towards functional endpoints, aligned with comorbidity-driven populations.
CONCLUSIONS: In rapidly evolving therapy areas, anticipating PICO requirements is constrained by lack of bespoke frameworks and stringent JCA requirements. Analysis of pivotal trial design provides a forward-looking lens on emerging standards of care, enabling early and more robust and proactive PICO scenario planning, in line with overall objectives of EU HTAR. Integrating trial design insights into PICO simulations can reduce uncertainty, better anticipate JCA requirements, and support HTDs to generate higher quality and more robust evidence for JCA.