Background: Despite international initiatives on collaboration within the field of rare diseases, patient access to orphan medicinal products (OMPs) and healthcare services differ greatly between countries. This study aimed to create a comprehensive and in-depth overview of rare diseases policies and reimbursement of OMPs in a selection of 12 countries in the Western Eurasian region: Armenia,

Background: Multi-criteria decision analysis (MCDA) is a decision-making tool that can take into account multidimensional factors and enables comparison of (medical) technologies by combining individual criteria into one overall appraisal. The MCDA approach has slowly gained traction within Health Technology Assessment (HTA) and its elements are gradually being incorporated into HTA across Europe. Several groups of scientists have proposed MCDA approaches targeted toward orphan drugs and rare diseases by including criteria specific to rare diseases. The goal of this article is to provide an overview of the current state of knowledge and latest developments in the field of MCDA in HTA for orphan drugs, to review existing models, their design characteristics, as well as to identify opportunities for further model improvement.Methods: A systematic literature search was conducted in January 2018 using four databases: MEDLINE (Pubmed), EBSCO HOST, EMBASE, and Web of science to find publications related to use of MCDA in the rare disease field (keywords: MCDA/orphan drug/rare disease and synonyms). Identified MCDA models were analyzed, e.g., structure, criteria, scoring, and weighting methodology.Results: Two hundred and eleven publications were identified, of which 29 were included after removal of duplicates. 9 authors developed own MCDA models, 7 of which based on literature reviews intended to identify the most important and relevant decision criteria in the model. In 13 publications (8 models) weights were assigned to criteria based on stakeholder input. The most commonly chosen criteria for creation of the MCDA models were: comparative effectiveness/efficacy, the need for intervention, and disease severity. Some models have overlapping criteria, especially in the treatment cost and effectiveness areas.Conclusions: A range of MCDA models for HTA have been developed, each with a slightly different approach, focus, and complexity, including several that specifically target rare diseases and orphan drug appraisal. Models have slowly progressed over the years based on pilots, stakeholder input, sharing experiences and scientific publications. However, full consensus on model structure, criteria selection and weighting is still lacking. A simplification of the MCDA model approach may increase its acceptance. A multi-stakeholder discussion on fundamental design and implementation strategies for MCDA models would be beneficial to this end.

The goal of this article is to provide an in-depth review of rare disease policies and the reimbursement of ODs in 3 European countries, two EU members (Poland, the Netherlands) and a non-EU one (Russia). A review of publicly available information on rare disorder policies and HTA processes was performed. Experts were consulted in case of unclear or scarce information. Russia has a five times higher frequency threshold for its rare disease definition than Poland and the Netherlands (both using the EU definition). The Netherlands has vastly increased its disease registries by instituting 300 expert centers via its National Plan, in Poland there are only 6 registries while in Russia one central registry exists. All 3 countries have an HTA process in place, however, the Russian one is relatively undeveloped. Access to ODs in the Netherlands is the broadest with 80 out of 83 EMA approved ODs reimbursed in 2015; Poland reimbursed 49, whereas Russia reimbursed 4 on the federal level and 43 in Moscow region. In all countries, new rare disease policies are under development. The availability of healthcare system solutions and the reimbursement of ODs differs greatly between all 3 countries. Even though both states are EU member with common regulations and access to EMA approved drugs, marked differences exist between Poland and the Netherlands in the range of policies, access to treatments and screening programs.

The European Union (EU) is continuously working towards further promoting and facilitating registration and development of orphan medicinal products (OMPs). The goal of this article is to present a broad overview of existing legislation, programmes and incentives in the EU that allow for accelerated access of orphan drugs and high medical need products, as well as give some historical context and how these programs are interconnected. The authors conducted an explorative review of publicly available sources of regulatory and orphan drug policies as well as information on accelerated assessment programs in the EU. The authors identified and looked into the following programs and initiatives: orphan drug legislation, accelerated assessment, conditional approval, Priority Medicine (PRIME), compassionate use programs, off-label use and RTU, Medicines Adaptive Pathways to Patients (MAPPs), ADAPT-SMART, HTA initiatives (EUnetHTA, Parallel Consultation), STAMP, IMI and IMI2 and the European Framework Programmes (incl. FP7 IDEAL, Asterix and Inspire). It can be concluded that promoting innovation and early access to medicines has been firmly put on the agenda in the EU, with various programs and initiatives, either national or EU-wide. Hurdles in regulatory science remain present, especially for rare diseases, but fundamental research as done in FP7 could lead to more efficient orphan drug development. Barriers in the field of HTA, pricing and reimbursement still need to be addressed to enhance patient access. The true effectiveness of all these programs will only become clear over time.

Diseases that are life-threatening or chronically debilitating are qualified as rare diseases (RD) in the EU if their prevalence is ≤ 5 per 10.000 (1, 2). One in 17 people in the EU (27 to 36 million people) suffer from one or more of the 6000-8000 rare diseases that exist (2, 3). Many rare diseases are characterized by an early/juvenile onset and a fast and progressive course of the disease, which makes early access to drugs paramount to stop disease progression and prevent irreversible organ and tissue damage (4). The level of access to orphan medicinal products