BACKGROUND: Reimbursement policies influence access of patients to orphan drugs in the European countries. OBJECTIVES: To provide a comprehensive description of orphan drug reimbursement policies and to assess reimbursement decision-making process in the EU-CEE countries as well as the impact of the type of approval and disease on reimbursement decisions. METHODS: For each drug, the information regarding conditional approval or approval under exceptional circumstances was obtained from the EMA website. The reimbursement status for analyzed drugs was collected in a questionnaire survey performed in a group of experts in reimbursement policy. The agreement between countries was assessed using the κ coefficient, nominal variables tests were compared using the χ2 test or the Fisher exact test. The impact of the EMA's conditional approval and approval under exceptional circumstances was assessed using logistic regression and presented as an odds ratio (OR). RESULTS: The analysis revealed that most orphan drugs were authorized for the treatment of oncological or metabolic diseases [36 drugs (38%) and 22 drugs (23%), respectively]. The shares of reimbursed orphan drugs varied significantly (p = 0.0031) from 6.3% in Latvia to 27.4% in Poland. No correlation (r = 0.02; p = 0.9583) with GDP per capita was observed. The highest agreement in reimbursement decisions was observed between Estonia and Lithuania, and the lowest - between Estonia and Latvia, with kappa of 0.69 and 0.11, respectively. Significant impact of the type of approval and reimbursement status was observed for Czechia, Lithuania and Slovakia where conditional approval and exceptional circumstances negatively influenced reimbursement decision. Type of disease has significant influence on reimbursement decision in 4 out of 10 analyzed countries with significant outweigh of positive decisions for oncological diseases. CONCLUSION: In considered countries specific regulations on reimbursement of orphan drugs are valid but in Lithuania and Romania no formal HTA process was employed; in case of some countries higher ICER values for orphans are used. The share of reimbursed orphan drugs varied significantly across the countries, but it was not associated with GDP per capita.

Agency for Medicinal Products and Medical Devices of Croatia Zagreb Croatia

Bioinformatics and Public Health Department Faculty of Medicine and Health Sciences Andrzej Frycz Modrzewski Krakow University Kraków Poland

Department of Biotechnology University of Rijeka Rijeka Croatia

Department of Organisation and Management in Pharmacy Faculty of Pharmacy Comenius University in Bratislava Bratislava Slovakia

Department of Pathology Forensic Medicine and Pharmacology Institute of Biomedical Sciences Faculty of Medicine Vilnius University Vilnius Lithuania

Department of Pharmacoeconomics Institute of Mother and Child Warsaw Poland

Faculty of Pharmacy Medical University of Sofia Sofia Bulgaria

Institute of Family Medicine and Public Health University of Tartu Tartu Estonia

Institute of Public Health Faculty of Health Sciences Jagiellonian University Medical College Kraków Poland

National Council on Prices and Reimbursement of Medicinal Products Sofia Bulgaria

National Institute of Health Insurance Fund Management Budapest Hungary

Pricing and Reimbursement Regulation Branch State Institute for Drug Control Prague Czechia

The National Health Service Riga Latvia

Titu Maiorescu University Bucharest Romania

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