Presentation (CTI)

OBJECTIVES: Many European health technology assessment (HTA) bodies require comparative effectiveness versus an appropriate comparator. The German Federal Joint Committee (G-BA) applies this requirement strictly. Misalignment between development, regulatory and market access functions, regional variations in evidence requirements, and heterogeneity in clinical practice can hinder choosing the right comparator. This could lead to unfavourable HTA outcomes, ultimately influencing achievable price and/or reimbursement. We aimed to analyse factors associated with inappropriate comparators in German HTA.
METHODS: G-BA benefit assessments published between 2015 and 2024 were reviewed in relapsed-refractory multiple myeloma, acute myeloid leukaemia, Waldenström’s macroglobulinemia, frontline metastatic breast cancer, metastatic cervical cancer, and metastatic castration-resistant prostate cancer. The association between comparator appropriateness and the location of the manufacturer’s headquarters (Europe or non-Europe), the manufacturer size (large multinational or smaller), indication (hemato-oncology or solid tumour) and being first-in-class (yes/no) was pairwise tested with Chi-square tests.
RESULTS: A statistically significant (α<0.05) association with comparator appropriateness was found in the case of the manufacturer’s size and the indication. Products developed by smaller companies and treatments for hemato-oncology were more prevalent among products with an inappropriate comparator compared to the expected, independent frequencies. Manufacturer geography and first-in-class status were not associated with comparator appropriateness.
CONCLUSIONS: Assessment reports were not sampled randomly, which limits the interpretability of the results and therefore they should be considered exploratory. However, data suggest that there could be an association between some product profile attributes and having an inappropriate comparator. Small companies could lack the expertise to deliver evidence packages meeting HTA requirements. Targeting complex and dynamic areas such as hemato-oncology increases the difficulty of selecting a compactor and the risk of trial comparators will be inappropriate or obsolete at the time of launch. In such cases, comparator considerations should be prioritized to anticipate potential challenges and prepare an evidence-generation strategy addressing those challenges.