Presentation (CTI)

OBJECTIVES: Health technology assessment (HTA) and Joint Clinical Assessment (JCA) require identifying clinically relevant comparators. As standards of care evolve, guideline recommendations may diverge from regulatory approvals through biomarker-driven therapies, sequencing changes, and off-label strategies. We evaluated the concordance between European Medicines Agency (EMA) approvals, European guideline recommendations and National Institute for Health and Care Excellence (NICE) decisions across six oncology indications and assessed implications for comparator selection through a Real-Time AI-Assisted Living Systematic Literature Review (REAL-SLR).
METHODS: A PRISMA-compliant, continuously updated REAL-SLR was used to identify interventional studies evaluating therapies with EMA approval and/or major European guideline recommendations in non-small cell lung cancer (NSCLC), bladder cancer (BC), prostate cancer (PC), pancreatic ductal adenocarcinoma (PDAC), multiple myeloma (MM), and chronic lymphocytic leukemia (CLL). Alignment between approval status, guideline recommendations and NICE decisions was monitored and assessed across indications.
RESULTS: As of June 17, 2026, the REAL-SLR contained 1,726 studies in NSCLC, 862 in PC, 751 in MM, 582 in PDAC, 554 in BC, and 341 in CLL. Of these, 412, 128, 182, 72, 28, and 97, respectively, evaluated EMA-approved/guideline-recommended therapies. Concordance between EMA-approved therapies and guideline recommendations varied across indications, from 92% in NSCLC and 91% in PC, 78% in CLL (78%), 75% in BC, 74% in MM, and only 49% in PDAC. Furthermore, only 36%-69% of studies with EMA-approved therapies have both guideline recommendations and NICE positive decisions. Divergence was primarily driven by older therapies no longer guideline-recommended, emerging therapies not yet approved, sequencing changes, and tumor-agnostic biomarker-driven strategies not yet adopted by guidelines.
CONCLUSIONS: Substantial differences exist between regulatory approvals, guideline recommendations and reimbursement decisions across oncology. Regulatory approvals alone may overestimate clinically relevant comparators, while guidelines reflect emerging standards of care. Living evidence monitoring enables earlier identification of comparator shifts, supporting HTA, JCA, reimbursement, and evidence-generation planning.