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.

Objectives: The aim of the study was to compare the access of patients with rare diseases (RDs) to biotechnological drugs in several Central and Eastern European countries (CEECs). We focused on the legislative pricing and reimbursement requirements, availability of biotechnological orphan medicinal products (BOMPs) for RDs, and reimbursement expenditures.Methods: A questionnaire-based survey was conducted among experts from 10 CEECs: Bulgaria, Croatia, Estonia, Greece, Hungary, Poland, Romania, Slovakia, Serbia, and Macedonia. The legal requirements for reimbursement and pricing of BOMPs were collected. All BOMPs and medicines without prior orphan designations were extracted from the European list of orphan medicinal products, 2017. The reimbursement status of these medicinal products in 2017 in the public coverage of the included CEECs as well as the share of their costs in relation to the total public pharmaceutical spending for the period from 2014 to 2016 were defined.Results: Our survey revealed that some differences in the legal requirements for pricing and reimbursement of BOMPs amongst the countries included in the study. All European Union countries have developed and implemented pharmacoeconomic guidelines with or without some specific reimbursement requirements for orphan medicinal products. Cost-effectiveness analysis, cost-utility analysis, Markov models, meta-analysis, and discount levels of costs and results were required only in Bulgaria, Poland and Hungary. The number of reimbursed BOMPs and biotechnological medicinal products for RDs without prior orphan designation was the highest in Hungary (17 and 40, respectively). Patient-based reimbursement schemes were available only in Hungary for 11 out of 17 BOMPs. Poland and Greece have the highest pharmaceutical expenditure of reimbursed BOMPs with are ~214 million and 180 million EUR, respectively in the observed period from 2014 to 2016. High proportion of the pharmaceutical expenditure on the reimbursed biotechnological medicinal products for RDs for the observed period 2014–2016 is presented in Bulgaria and Slovakia.Conclusions: The non-European Union CEECs face a significant delay in the legal implementation of pharmacoeconomic guideline for assessment of BOMPs. The access to BOMPs is similar among the observed CEECs and the countries with the best access are Hungary and Greece. The influence of BOMP expenditures on the budget in the individual countries is significant.

Objectives: Utilization of multisource biological (off-patent originator and its biosimilar) medicines can improve the efficiency of resource allocation by 1) generating savings while maintaining health outcomes or 2) increasing the number of patients treated with more affordable treatments. This study evaluates the efficiency of the Hungarian biosimilar drug policy on the case of biosimilar infliximab. Methods: We analyzed the utilization of biologicals in all reimbursed indications of infliximab including initial therapy of new patients and switching patterns retrospectively based on patient-level payer's data between September 2012 and December 2016. Results: Despite the economic rationale, patent expiry did not manifest in increased utilization of multisource infliximab in an access-restricted environment: 1) Patients previously treated with original biologicals were switched mainly to other original biologicals instead of more affordable biosimilar alternatives. 2) Although some treatment-naive patients started on more affordable multisource infliximab with price competition, the majority of new patients started on other original biologicals with monopolistic price. Conclusion: Policy tools and measures should be developed to facilitate first-line use of multisource biologicals for treatment-naive patients and promoting the use of more affordable multisource biologicals in case of switching. ARTICLE HISTORY

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.

S95excluded specialty drugs indicated for cancer. We included 2,405 coverage decisions (current April 2016) pertaining to 203 drug-indication pairs (drugs were often indicated for multiple indications). We assessed the following independent variables: safety warnings (black box warning or inclusion in REMS program); availability of alternative interventions; orphan drug; pediatric indication; FDA expedited approval; years since FDA approval; self-administered; annual cost; and budget impact. We used multi-level multivariate logistic regression to determine factors associated with restricted coverage. We selected the final model using the Akaike's Information Criterion. ReSultS: The following variables were positively associated with restricted coverage: safety warnings (adjusted odds ratio,