Presentation (CTI)

OBJECTIVES: Although Overall Survival (OS) remains the gold standard for HTA Agencies, certain inherent limitations may affect its appropriateness in settings where timely access is required. Alternative (surrogate/early) endpoints can measure treatment effects earlier and be more sensitive in specific contexts. However, their clinical relevance is uncertain and requires validation of their surrogacy with OS: this uncertainty impacts HTA evaluations and reimbursement decisions. This study aims to identify when and in which contexts surrogate/early endpoints are considered robust enough to support access and reimbursement assessment.
METHODS: A qualitative, comparative and document-based analysis was conducted across three onco-hematological settings (i.e., acute myeloid leukemia, LMA; classical Hodgkin lymphoma, cHL; diffuse large B-cell lymphoma, DLBCL). A scoping literature review enabled: 1) the establishment of three databases of pivotal clinical trials; 2) the identification of the biological and clinical rationale behind endpoint selection; 3) the assessment of surrogacy between OS and alternative endpoints; and 4) the comparison of stakeholder perspectives, including clinical, patient and payer views.
RESULTS: Endpoint relevance appears to be disease- and context-dependent. In high-mortality conditions (LMA) OS remains the most robust endpoint to capturing overall clinical benefit, supporting reimbursement decisions. In diseases with high cure rates and long survival (cHL), Progression-Free Survival (PFS) better reflects both efficacy and treatment burden, showing strong surrogacy with OS and increasing acceptance among payers. In aggressive yet potentially curable settings (DLBCL), endpoint selection varies by treatment line: time-to-event and response-based endpoints are commonly used despite residual uncertainty, as they capture clinical benefit and inform pricing and reimbursement decisions.
CONCLUSIONS: No universal hierarchy of endpoints exists. Endpoint selection should be disease-specific and aligned with disease biology, clinical trajectory, decision-making needs, and their robustness. Moving beyond an OS-centric paradigm towards a contextual, multi-endpoint framework is essential to merge scientific rigor, HTA constraints, and timely patient access.