Health Economic Evaluation of Technologies for Rare Diseases: A Critical Review of International Approaches

Background : Rare diseases pose specific challenges to health systems due to their low prevalence, clinical complexity, and the uncertainties surrounding their treatment. The emergence of orphan drugs has led to major therapeutic advances but also raises ethical and economic questions, particularly in terms of health economic evaluation. Objective : This article aims to provide a critical review of the health economic methods used internationally to evaluate health technologies for rare diseases, by identifying innovations, limitations, and common trends in the approaches adopted by major assessment agencies. Method : A critical narrative review was conducted using academic sources (PubMed, Scopus, Web of Science) and institutional reports (NICE, HAS, CADTH, IQWiG, AIFA, ICER, ZIN) between April and May 2025. The selected documents cover the period 2010–2025 and focus on the economic evaluation of orphan drugs and related technologies. Results : The analysis reveals a diversity of approaches across countries, but also identifies converging trends: proactive management of uncertainty (MAA, MEA, RWE), expansion of value criteria (equity, severity, innovation), increased flexibility in the use of clinical evidence, and greater patient involvement. However, divergences remain in the formalization of ICER/QALY thresholds and the institutional use of real-world data. Conclusion: A minimum level of international convergence in evaluation standards is desirable to ensure equity, transparency, and efficiency in the assessment of health technologies for rare diseases, while allowing for methodological adaptation to national contexts.