Presentation (CTI)

OBJECTIVES: For disease-modifying therapies (DMTs), the value proposition is dependent on long-term extrapolation of benefits. Economic value hinges on assumptions - natural history progression, treatment durability, and surrogate-to-outcome relationships - made years before mature evidence is available. Early economic models (EEMs) are becoming a strategic necessity to reduce decision uncertainty. Despite this, no DMT-specific framework currently exists to guide EEM across the development lifecycle. We aimed to develop a strategic framework for EEMs of DMTs for informed decision-making.
METHODS: The framework was developed based on a targeted review of EEM publications (2010-2025) and National Institute for Health and Care Excellence (NICE) Technical Support Documents, iteratively refined through our applications of EEMs for DMTs in a chronic respiratory disease, a neurodegenerative disease, and a metabolic liver disease.
RESULTS: A framework was developed to operationalise identified methodological imperatives across the product development stages: preclinical/Phase I (conceptual model, natural history modelling), Phase II (structural scenarios, sensitivity analysis), Phase III (HTA-aligned architecture, external validation), and peri-launch (value-based pricing, managed access, RWE integration). The framework prescribes five methodological imperatives for DMT EEMs: (1) externally validated baseline natural history (observed ~50% incremental cost-effectiveness ratio [ICER] deviation between two natural history sources in liver disease model); (2) pre-specified, stress-tested structural assumptions, including progression formulation, treatment waning, and surrogate-to-outcome link functions; (3) explicit causal chain encoding from mechanism through biomarker to patient-relevant outcome; (4) value-of-information analysis to quantify decision uncertainty and prioritise evidence generation; and (5) cross-jurisdiction adaptability through harmonised model architecture anticipating Joint Clinical Assessment (JCA)-determined scope.
CONCLUSIONS: The framework structures DMT economic modelling around key imperatives across four lifecycle stages, providing a roadmap for manufacturers to address DMT-specific structural and evidential challenges. Structural assumptions drive early DMT value, as our finding of a 50% change in the ICER suggests, warranting priority evidence generation from preclinical development onwards.