Presentation (CTI)

OBJECTIVES: Orphan medicinal products (OMPs) face structural evidence constraints, including small and heterogeneous populations, single-arm trials, reliance on external comparators, surrogate endpoints, and immature long-term data. They are also associated with high unmet need, severe disease burden, frequent pediatric involvement, and significant ethical considerations. These characteristics limit the applicability of conventional cost-utility analysis and increase reliance on broader value elements such as severity, unmet need, equity, caregiver impact, and innovation in a qualitative way and/or in the deliberative process. In this context, explicitness—the degree to which value elements are formally defined, required, and systematically applied—becomes important. The aim of this study is to assess the explicitness of 20 broader value elements across 12 European HTA systems and identify structural patterns in how value considerations are formalized for OMPs.
METHODS: A structured document analysis and triangulation was applied to Belgium, England, France, Germany, the Netherlands, Sweden, Spain, Italy, Portugal, Ireland, Hungary and Poland. Each value element was coded as: Explicit (E), Qualitative (Q), or Not considered (N), with hybrid categories (E/Q, N/Q) capturing partial inclusion. Data sources included national pharmacoeconomic guidelines, HTA manuals, and publicly available national HTA documents.
RESULTS: Only patient health gain and direct medical costs (except Germany) were explicit across countries. Severity was explicit in most systems but operationalised differently. Other elements—unmet need, innovation, equity, caregiver impact, value of hope, and real option value—were rarely explicit and predominantly qualitative and deliberative. Productivity and informal care showed substantial heterogeneity. Four HTA archetypes emerged: Formalised (England, Netherlands, Sweden); Deliberative (Belgium, Spain, Italy, Portugal, Ireland); Clinically rigid (Germany, Poland); Hybrid (France, Hungary).
CONCLUSIONS: Explicitness—not the presence of value elements—drives cross-country variation in OMP HTA. Strengthening explicitness may improve predictability, consistency, and alignment under the EU HTA Regulation.