Objective: To assess shares of reimbursed orphan drugs and agreement in reimbursement decision-making in different European Union member states as well as to define odds for reimbursement influenced by the presence of conditional approval or exceptional circumstances granted by the European Medicines Agency (EMA) or by type of the disease.Methods: The list of authorized drugs with current orphan designations was collected from the website of the EMA. For each drug, the information regarding conditional approval or approval under exceptional circumstances was collected. The reimbursement statuses were available on national reimbursement or HTA agencies websites. The agreement for reimbursement decisions between selected countries was assessed using the κ coefficient for the measurement of agreement. The impact of the EMA's conditional approval as well as approval under exceptional circumstances was assessed using the logistic regression and presented as odds ratio.Results: The percentage of reimbursed orphan drugs varied significantly from 27% in Poland to 88% in Denmark, with an average value of 51% (p < 0.0001). Regarding the reimbursement status, the highest, substantial agreement was observed between Spain and Italy, and the lowest agreement was observed between Germany and England, with κ of 0.64 and 0.01, respectively. Conditional approval status significantly decreased the chance for reimbursement in France, Italy, and Spain by 77–80%; however, approval granted under exceptional circumstances had significant impact only in Germany with 85% decrease in chances for reimbursement. The type of the disease (oncology or metabolic) was significantly associated with both conditional approval (p of 0.03—oncology drugs were more likely to be conditionally approved then the rest of analyzed drugs) and exceptional circumstances (p of 0.02—drugs for metabolic diseases were more likely to be approved under exceptional circumstances).Conclusions: Access to reimbursed orphan drugs varies significantly across EU countries. The highest, substantial agreement in reimbursement decisions was observed between Italy and Spain and the lowest between Germany and England. Conditional approval and approval under exceptional circumstances were significant negative predictors of reimbursement in some countries and they were significantly associated with the type of the disease (oncology or metabolic).

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.

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Background The reimbursement of orphan drugs (OD) is an increasingly important for country policymakers, and still insufficiently understood, especially in Central and Eastern Europe. The aim of this research was to provide a comprehensive description of country-specific health technology assessment (HTA) policies as well as evaluate the percentage of HTA recommendations and reimbursement decisions for oncology OD. In addition, the study was designed to elucidate the impact of reimbursement of these drugs on the public budget and the agreement between HTA recommendations and reimbursement decisions in the analysed countries. A questionnaire survey was used to collect data on the reimbursement status, HTA recommendation, marketing authorisation, and public expenses on reimbursement in 2014, 2015, and 2016 for all oncology drugs with an orphan designation by the European Medicine Agency in 2017 in Bulgaria, Croatia, Czechia, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, and Slovakia. The agreement between the HTA recommendation and reimbursement status was assessed using the kappa coefficient. The Pearson’s correlation was used to analyse the relationship between gross domestic product (GDP) and GDP per capita and reimbursement expenses. Results A total of 36 drugs were analysed (25% conditionally approved; 5.56% approved under exceptional circumstances). The share of reimbursed drugs ranged from 11.11% in Latvia to 41.67% in Poland. The highest share of positive recommendations was observed for Bulgaria and Estonia (36.11%), and the lowest, for Latvia (11.11%). The agreement varied from 0.4 for Poland to 1 for Latvia, Hungary, and Slovakia. Expenses were correlated with GDP (0.95 [0.81–0.99]), and not with GDP per capita (0.54 [− 0.136 to 0.873]). Expenses per capita were not correlated with GDP per capita (0.52 [− 0.15 to 0.87]). Conclusions In Hungary, Latvia, and Slovakia, a positive recommendation was associated with a reimbursement, and a negative one, with the lack of reimbursement. The reimbursement of oncology OD is associated with a growing burden for public budget, and the expenses are correlated with the total GDP. The highest share of drugs with any recommendation was observed in Poland, and the lowest, in Latvia and Romania. The share of reimbursed drugs was the lowest in Latvia and the highest in Poland.

Our study revealed a fair agreement between the AOTMiT recommendations and the MoH decisions; the association was especially weak in 2015.