OBJECTIVES: Orphan drugs (ODs) face challenges in demonstrating clinical value due to limitations in clinical trial design. While some European health technology assessment (HTA) agencies have developed OD-specific frameworks, no OD-specific framework has been publicly disclosed for the implementation of JCA on ODs from 2028 onwards. This research aims to identify OD frameworks used at national level and explore challenges related to the JCA implementation in ODs using the current JCA framework.

METHODS: Secondary research was conducted between 2018‑2024 to identify OD frameworks currently being used by national HTA agencies in Europe. The EUnetHTA website was explored to identify any OD-specific considerations in the existing publicly available JCA framework.

RESULTS: The HTA agency in Germany has an OD framework that considers additional benefit proven for ODs if the annual budget impact on total sales is <€30 million, with some flexibility while assessing statistically significant comparisons and surrogate endpoints. Furthermore, while ODs follow standard assessment by HTA agencies in France and Sweden, more flexibility is applied in their decision-making criteria (e.g., acceptability of surrogate endpoints, historical controls). The Scottish HTA agency considers factors such as quality of life, impact on family life or work, unmet need, or disease severity when assessing ODs, while the English HTA agency may accept higher degree of uncertainty for some rare conditions.

CONCLUSIONS: Manufacturers must consider the implications of JCA reports for HTA agencies that apply formal OD frameworks and flexible approaches. In countries where clinical benefit is a key decision driver, the lack of an OD-specific framework may have minimal impact, but additional clarification on data may be requested. In countries where cost-effectiveness is also a decision driver, the incorporation of JCA reports into the decision-making‑ process for ODs is still uncertain. Early strategic planning on economic models or managed entry agreements may help to navigate this uncertainty.