Presentation (CTI)

OBJECTIVES: Wide variation in key determinants of decision-making is typically observed across EU HTA. With the introduction of joint clinical assessment (JCA), it is unknown which factors will drive decisions. This review aims to characterize key critiques of the clinical evidence in melanoma, one of the first therapy areas to undergo JCA.
METHODS: We performed a targeted review of HTA reports in melanoma published between May 2020 and 2025, across 4 HTA sites (HAS, IQWiG, AEMPS, and ZIN). Common themes from appraisals of the clinical evidence were extracted and compared.
RESULTS: A total of 21 HTA reports encompassing 7 technologies were identified. HAS and IQWiG had the lowest rate of positive assessments of clinical benefit and were aligned in their criticism of immature overall survival data, inappropriate comparators, and incomplete quality-of-life data. In contrast, AEMPS and ZIN frequently emphasized clinical relevance and AEMPS particularly commented on trial design. All 4 HTA agencies commented on extrapolation of data from adults to adolescents but generally accepted this approach aside from IQWiG. ZIN, HAS, and IQWiG commented on the uncertainty of results from indirect treatment comparisons. Both IQWiG and ZIN explicitly evaluated the quality of evidence provided by the company, with IQWiG consistently assessing risk of bias, while ZIN used the GRADE method. Key drivers of decision-making common to all HTA agencies included unmet need, trial sample size, completeness of patient-reported outcomes data, and uncertainty of long-term treatment effect.
CONCLUSIONS: HTA agencies differed in their critique of the same data, resulting in conflicting appraisal outcomes. With JCA set to standardize clinical evidence submissions, it may be difficult for companies to align their submissions with country-specific expectations. Moreover, given the different areas of emphasis between agencies, it is currently unknown how assessor agencies will influence JCA outcomes and whether these will be reflective of EU-wide HTA decision-making.