Presentation (CTI)

OBJECTIVES: On paper, the HTAR is evidence-neutral, requiring relative clinical effects to be assessed from the available evidence. In practice, some evidence appears to count more than others. This study evaluated whether an implicit evidence hierarchy is developing within the JCA framework and assessed its implications for innovative therapies.
METHODS: A qualitative methodological review was undertaken using HTAR provisions, methodological guidance, and published analyses of early JCA implementation. Evidence acceptance patterns were examined across five domains: randomised controlled trials, real-world evidence (RWE), surrogate endpoints, single-arm trials, and uncertainty assessment frameworks. Regulatory standards used by the European Medicines Agency (EMA) were compared with evolving JCA practices.
RESULTS: The findings suggest the emergence of an implicit evidence hierarchy characterised by preferential weighting of randomised controlled trials and overall survival outcomes. Real-world evidence is frequently treated as supportive rather than decision-driving evidence. Surrogate endpoints accepted by regulatory authorities may receive limited consideration during relative effectiveness assessments. Single-arm trials, commonly used in rare diseases and advanced therapies, encounter particular challenges due to the absence of dedicated assessment frameworks. The result is a potential divergence between evidence considered sufficient for marketing authorisation and evidence considered sufficient for HTA purposes. This divergence is especially relevant for oncology, rare diseases, and advanced therapies, where traditional comparative evidence may be difficult or impossible to generate.
CONCLUSIONS: If some evidence will count for less, developers deserve to know that in advance. Methodological guidance should state explicitly how real-world evidence, surrogate endpoints, and single-arm data will be weighed — especially where randomised evidence is infeasible.