Presentation (CTI)

OBJECTIVES: HTA bodies frequently issue negative or restrictive early decisions where uncertainty persists in clinical evidence, comparators, populations or economic value. This study aimed to identify key drivers of early negative HTA decisions in oncology appraisals to improve first-time decision success.
METHODS: A review of publicly available appraisal documents published by the UK, France and Germany HTA bodies (June 2025-May 2026) was conducted. Indications in solid tumours were selected as a focus due to their high volume of HTA activity, evolving standards of care and reliance on complex comparative evidence packages. Appraisals were categorized by outcome, and common drivers of negative HTA decisions identified across agencies.
RESULTS: Across all three countries, uncertainty in comparative effectiveness emerged as the most consistent and cross-cutting driver of negative or restrictive outcomes (UK:16/34; France:14/20; Germany:35/38), often linked to absence of head-to-head data. Comparator misalignment was a key driver influencing outcomes in Germany (25/38), but also evident in the UK and France where trial comparators did not reflect local healthcare practice (UK:13/34; France:12/20). Immature or non-robust survival data was another common theme (UK:13/34; France:10/20; Germany:7/38), contributing uncertainty in both clinical benefit and cost-effectiveness. A key driver included economic modelling limitations (17/34); these issues were frequently addressed through evidence refinement, with 11 technologies ultimately reversing early non-recommendations in the UK. In contrast, reversal of prior unfavourable decisions was less frequent in France and Germany. Notably, these drivers frequently co‑occurred within individual appraisals, where their combined effect was associated with negative HTA decisions.
CONCLUSIONS: Early negative HTA outcomes are largely driven by a consistent set of overlapping, addressable evidence uncertainties across agencies, despite differences in decision frameworks. Proactive alignment on comparator selection, earlier generation of robust comparative data and strategies to mitigate survival data immaturity are critical to improving first-time HTA success and enabling more consistent outcomes across markets.