Reimbursement of Orphan Drugs in Europe in Relation to the Type of Authorization by the European Medicines Agency and the Decision Making Based on Health Technology Assessment

Abstract

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).

A Review of Rare Disease Policies and Orphan Drug Reimbursement Systems in 12 Eurasian Countries

“…(41), Turkey 6 (40, 42) 10 . Armenia 4 , Kazakhstan 11 (43), Latvia and Romania 12 (44,45), only screen for phenylketonuria and congenital hypothyroidism. England, Scotland, and Wales screen for nine diseases, whereas Northern Ireland (part of the UK as well) screens only for 5 (29) 13,14 .…”

“…Rare disease policies are a high focus area, given the medical need surrounding rare diseases and the relatively large impact these diseases and their treatment potentially have on healthcare budgets. The reimbursement status of orphan drugs in Eastern Europe has been described by several authors recently (11)(12)(13)(14)(15). There have been multiple publications describing OMP policies in Central and Eastern Europe in single countries (16)(17)(18) or covering a larger number of countries in Europe (5,(19)(20)(21)(22).…”

Health technology assessment and reimbursement policy for oncology orphan drugs in Central and Eastern Europe

“…In most cases, after the initial approval of the drug, some new clinical data regarding drug efficacy would emerge and could influence reimbursement decisions. Although the Committee of Human Medicinal Products does not have any direct influence on prising policy in European Union (EU) member states, the type of approval could be considered in the decision-making process [5]. Additionally, in this study, we focused on the analysis of growing expenditures in relation to growing GDP without considering the effect of various factors on the expenditures to reveal the burden of oncology orphan drugs on the public budget.…”

“…In order to compare the results of our study, we reviewed medical databases to identify other important publications on this subject. Our previous study [5] analysed the status of all drugs with orphan designation and their relation to the type of EMA approval. In addition, we showed a significant variation in agreement with the reimbursement status of analysed drugs across selected European countries.…”

“…It is becoming increasingly popular in CEE countries to implement special regulations regarding the reimbursement of orphan drugs, which affects not only the decision-making process but also the procedures of developing HTA recommendations and requirements [5]. The reimbursement of orphan drugs is the main determinant of patients' access to innovative therapies, with the better availability of treatments in western European countries, as shown by German and French research [5,14]. However, no sub-analysis for oncology orphan drugs was performed in relation to the CEE countries which are characterised by limited access to orphan biotechnological drugs, with Macedonia and Estonia having only one drug reimbursed, followed by Romania and Serbia with two drugs reimbursed, Bulgaria with three drugs reimbursed, Slovakia with four drugs reimbursed, and Croatia with seven drugs reimbursed [16].…”