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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.00487

Reimbursement legislations and decision making for orphan drugs in Central and Eastern European countries

 Krzysztof P. Malinowski1*, Paweł Kawalec1, Wojciech Trąbka2, Marcin Czech3,  Guenka I. Petrova4,  Manoela Manova4, 5,  Alexandra T. Savova4, 5,  Pero Draganic6, 7,  Lenka Vostalova8, Juraj Slaby8,  Agnes Männik9, Kristóf Márky10, Zinta Rugaja11,  Jolanta Gulbinovic12,  Tomas Tesar13 and  Marian S. Paveliu14
  • 1Institute of Public Health, Faculty of Health Science, Jagiellonian University Medical College, Poland
  • 2Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski Krakow University, Poland
  • 3Institute of Mother and Child, Poland
  • 4Faculty of Pharmacy, Medical University of Sofia, Bulgaria
  • 5National Council on Prices and Reimbursement of Medicines, Bulgaria
  • 6Agency for Medicinal Products and Medical Devices of Croatian, Croatia
  • 7Department of Biotechnology, University of Rijeka, Croatia
  • 8State Institute for Drug Control, Czechia
  • 9Institute of Family Medicine and Public Health, Faculty of Medicine, University of Tartu, Estonia
  • 10National Health Insurance Fund of Hungary, Hungary
  • 11National Health Service (Latvia), Latvia
  • 12Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, Lithuania
  • 13Department of Organization and Management in Pharmacy, Faculty of Pharmacy, Comenius University in Bratislava, Slovakia
  • 14Titu Maiorescu University, Romania

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 analysed 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 authorised 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 Czech Republic, 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 analysed countries with significant outweigh of positive decisions for oncological diseases. Conclusions: 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.

Keywords: orphan drug, Reimbursement policy, Central and East Europe (CEE), European Medicine Agency (EMA), Kappa coefficient of agreement, Marketing authorisation, Exceptional circumstances (EC), Conditional approval

Received: 23 Feb 2019; Accepted: 17 Apr 2019.

Edited by:

Brian Godman, Karolinska Institute (KI), Sweden

Reviewed by:

Domenico Criscuolo, Italian Society of Pharmaceutical Medicine, Italy
Robert L. Lins, Independent researcher
Wil Toenders, ToendersdeGroot B.V., Netherlands  

Copyright: © 2019 Malinowski, Kawalec, Trąbka, Czech, Petrova, Manova, Savova, Draganic, Vostalova, Slaby, Männik, Márky, Rugaja, Gulbinovic, Tesar and Paveliu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mr. Krzysztof P. Malinowski, Institute of Public Health, Faculty of Health Science, Jagiellonian University Medical College, Krakow, 31-531, Poland,