Health Technology Assessment Guidelines and Recommendations Across European Union Countries and the United Kingdom in Rare Disease and Paediatric Populations.

Objectives: Due to limited clinical data, high uncertainty, and outcome variability, assessing therapies for paediatric and rare disease populations poses specific challenges, often requiring adjustments to standard health technology assessment (HTA) frameworks. This study examines how national HTA guidelines and recommendations across Europe reflect these demands, identifying methodological adaptations and country-specific disparities.

Methods: HTA organisations across the 27 EU Member States and the UK were identified via INAHTA, EUnetHTA, and ISPOR reference listings. Publicly available documents were screened, and 29 relevant national guidelines were selected. A structured document analysis was performed using a predefined coding framework. Key terms were systematically searched, and content was categorised into thematic domains.

Results: Among the 29 guidelines, 16 included references to rare disease populations, and 12 to paediatric populations. For paediatric populations, most references focused on quality-of-life measurement and proxy assessments. Adaptations for rare diseases recognised flexible cost-effectiveness thresholds (e.g. adjusted incremental cost-effectiveness ratios [ICERs] or gross domestic product [GDP]-based modifiers), tailored economic modelling, and acceptance of alternative data sources. However, significant variability was observed across countries, with no consistent pattern.

Conclusion: While several HTA bodies have introduced adjustments for paediatric and rare disease populations, guidance often remains limited and heterogeneous. The findings indicate that HTA guidelines and recommendations require further collaboration to properly define and account for the specific needs of these patients. Methodological shortcomings are mainly due to the nature of these diseases, where the limited data available are primarily from clinical practice and often lack comparative effectiveness evidence.