Presentation (CTI)

OBJECTIVES: Rapidly evolving oncology treatment pathways may create misalignment between pivotal trial comparators and those considered clinically relevant during HTA appraisals, potentially influencing evidence generation, value assessment, and reimbursement decisions. We explored how evolving standards of care (SoC) influence comparator relevance across major European HTA agencies and assessed alignment with contemporary clinical practice.
METHODS: A targeted review of publicly available oncology HTAs published between May 2023 and May 2026 was conducted, using NICE (UK) appraisals as a starting point and cross-validated against G-BA (Germany), HAS (France), and AEMPS (Spain). AIFA (Italy) was excluded due to limited public comparator data. HTAs for innovative therapies in advanced/metastatic solid tumors with documented comparator challenges or evolving treatment pathways were included. Comparator frameworks, appraisal outcomes, and comparator-related challenges were qualitatively compared across jurisdictions.
RESULTS: Seven case studies were included. Comparator relevance challenges were identified across all reviewed HTAs, with extent and consequence varying by jurisdiction. Three recurring patterns emerged: (a) where biomarker-driven or targeted pathways were well-established, non-chemotherapy comparators were accepted, but immature comparative evidence and reliance on indirect comparisons still introduced uncertainty in value assessment; (b) chemotherapy-based comparators frequently remained the reference point despite the emergence of targeted and immunotherapy-based alternatives, creating misalignment between trial evidence and contemporary clinical practice; and (c) clinically relevant non-chemotherapy alternatives were sometimes acknowledged by HTA bodies but not fully incorporated into assessments, leaving evidence gaps that limited demonstration of comparative value. Across all three patterns, challenges were amplified when SoC evolved between trial design and HTA appraisal, increasing reliance on indirect evidence and contributing to uncertainty in reimbursement decision-making.
CONCLUSIONS: Comparator frameworks in oncology HTAs do not always keep pace with evolving SoC. Further research and cross-stakeholder dialogue are needed to evolve comparator selection methodologies and support more contemporaneous HTA decision-making in rapidly changing treatment settings.