Orphan Medicine Policy and Decision-Making Frameworks: A Narrative Review of Hta Methodologies Publisher



Mobinizadeh M ; Padula WV ; Jen MH ; Mohamadi E ; Salehi S
Source: Health Policy and Technology Published:2026

Abstract

Objectives: Orphan medicinal products (OMPs) often face unique policy and reimbursement challenges due to small patient populations, limited clinical data, and high costs. This review aims to provide the first comprehensive, cross‑methodological and cross‑stage synthesis of how CEA, GCEA, MCDA, and BIA have been applied in OMPs policymaking, addressing critical gaps in integrating findings across HTA stages and income‑level contexts. Methods: This narrative review searched PubMed and Google Scholar for English‑language studies published between 2008 and 2024, using keywords related to rare diseases, policymaking, and the three key stages of the health technology policymaking process: topic selection, assessment, and appraisal. Studies were included if they addressed at least one of these stages in the context of OMPs. Results: This review identified 17 studies related to policymaking for orphan medicinal products, of which 6 focused on topic selection—including 3 that explicitly examined horizon scanning—and 11 on the combined assessment and appraisal stages. Methodologically, 3 studies applied CEA or GCEA, 8 explored MCDA (2 for topic selection and 6 for assessment and appraisal stages), and 2 employed BIA, with some studies using more than one approach. CEA serves as the standard but struggles to incorporate societal, ethical, and dynamic market factors, often limiting its applicability for OMPs. GCEA addresses such gaps with additional considerations like disease severity and equity but remains methodologically complex. MCDA offers a more comprehensive framework by integrating clinical, economic, and qualitative benefits, although challenges like attribute weighting and stakeholder inclusion persist. BIA is instrumental in assessing affordability but lacks clinical outcome integration. Additionally, Managed Entry Agreements (MEAs) although not an HTA methodology in themselves - have emerged in several countries as practical policy tools for mitigating financial risk and bridging evidence gaps, thereby complementing the application of CEA, GCEA, MCDA, and BIA in real‑world OMPs decision‑making. Conclusion: Integrating GCEA, MCDA, BIA, and complementary tools such as MEAs alongside systematic horizon scanning within the topic selection stage creates a robust framework for addressing the complexities of orphan drug policymaking across all HTA stages. Future work should focus on developing a technical input–output design for the proposed integrated chain HTA model, ensuring that outputs from horizon scanning and topic selection feed directly into structured assessment modules, and that appraisal outputs are systematically linked to policy tools such as MEAs and BIA. © 2025 Fellowship of Postgraduate Medicine