Presentation (CTI)

OBJECTIVES: To develop and test a structured, transparent framework for early PICO (Population, Intervention, Comparator, Outcome) definition and prioritization to support preparation for Joint Clinical Assessment (JCA) submissions. Design approach to anticipate decision‑relevant scenarios for oncology products by aligning published evidence, HTA expectations, and clinical guidelines in non-small cell lung cancer (NSCLC) with disease progression after at least one prior systemic therapy as an example. This framework was applied and tested using the published PICO examples from the European Commission (EC), specifically the adagrasib exercise as the primary validation reference
METHODS: The structured framework had six-steps: (1) define the therapeutic context (advanced NSCLC with KRAS G12C mutation and disease progression) and profile candidate therapies; (2) conduct systematic searches in PubMed, ClinicalTrials.gov, and key HTA/guideline sources; (3) extract data on eligible PICOs; (4) construct a PICO matrix integrating prevalence and probability data; (5) validate scenarios using expert feedback; and (6) refine strategy and additional evidence needs. AI-based tools supported project management, evidence curation, and systematic PICO generation and prioritization.
RESULTS: For the NSCLC population of interest 32 PICO scenarios across five patient subgroups were generated. In the all-comer previously treated population, evidence was strongest for chemotherapy [docetaxel, pemetrexed] (n=39), antiangiogenic combinations [e.g., ramucirumab + docetaxel] (n=29), and immune checkpoint inhibitors [pembrolizumab, nivolumab, atezolizumab] (n=26). Although sotorasib represents the most clinically relevant direct comparator in KRAS G12C-specific PICOs, few supporting studies were identified, consistent with the emerging nature of this drug class. The prioritized list, including key outcomes aligned well with EC's published PICOs.
CONCLUSIONS: An integrated, semi-automated framework can enable accelerated, early PICO development for JCA in line with EU requirements, as illustrated in NSCLC. Our proactive methodology using an AI-based support tool can streamline scenario assessment, improve consistency and auditability, and deliver submission-ready evidence to enhance JCA readiness and compliance for all therapies.