BackgroundIn case of orphan drugs applicability of the standard health technology assessment (HTA) process is limited due to scarcity of good clinical and health economic evidence. Financing these premium priced drugs is more controversial in the Central and Eastern European (CEE) region where the public funding resources are more restricted, and health economic justification should be an even more important aspect of policy decisions than in higher income European countries.ObjectivesTo explore and summarize the recent scientific evidence on value drivers related to the health technology assessment of ODs with a special focus on the perspective of third party payers in CEE countries. The review aims to list all potentially relevant value drivers in the reimbursement process of orphan drugs.MethodsA systematic literature review was performed; PubMed and Scopus databases were systematically searched for relevant publications until April 2015. Extracted data were summarized along key HTA elements.ResultsFrom the 2664 identified publications, 87 contained relevant information on the evaluation criteria of orphan drugs, but only 5 had direct information from the CEE region. The presentation of good clinical evidence seems to play a key role especially since this should be the basis of cost-effectiveness analyses, which have more importance in resource-constrained economies. Due to external price referencing of pharmaceuticals, the relative budget impact of orphan drugs is expected to be higher in CEE than in Western European (WE) countries unless accessibility of patients remains more limited in poorer European regions. Equity principles based on disease prevalence and non-availability of alternative treatment options may increase the price premium, however, societies must have some control on prices and a rationale based on multiple criteria in reimbursement decisions.ConclusionsThe evaluation of orphan medicines should include multiple criteria to appropriately measure the clinical added value of orphan drugs. The search found only a small number of studies coming from CEE, therefore European policies on orphan drugs may be based largely on experiences in WE countries. More research should be done in the future in CEE because financing high-priced orphan drugs involves a greater burden for these countries.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-016-0455-6) contains supplementary material, which is available to authorized users.

BackgroundSanfilippo syndrome (mucopolysaccharidosis [MPS] III subtypes A, B, C, and D) is a rare autosomal recessive inherited metabolic disorder that causes progressive neurocognitive degeneration. This systematic literature review was undertaken to compile and assess published epidemiological data, including various frequency measures and geographical variation on Sanfilippo syndrome.MethodsThe following databases were systematically searched for terms related to Sanfilippo syndrome epidemiology: Medline, Embase, Cochrane Database of Systematic Reviews, Academic Search Complete, Cumulative Index to Nursing and Allied Health Literature, and the Centre for Reviews and Dissemination. Qualitative synthesis of research findings was performed.ResultsOf 2794 publications found in the initial search, 116 were deemed eligible after title and abstract screening. Following full-text review, 46 papers were included in the qualitative synthesis. Results of this systematic literature review indicate that lifetime risk at birth ranges from 0.17–2.35 per 100,000 live births for all 4 subtypes of MPS III together, and from 0.00–1.62 per 100,000 live births for the most frequent subtype, MPS IIIA.ConclusionAll 4 subtypes of MPS III are exceptionally rare, but they each have devastating effects on children. Higher-quality epidemiological data are needed to appropriately target resources for disease research and management.Electronic supplementary materialThe online version of this article (10.1186/s13023-018-0796-4) contains supplementary material, which is available to authorized users.

Methylmalonic acidemia/aciduria (MMA) is a genetically heterogeneous group of inherited metabolic disorders biochemically characterized by the accumulation of methylmalonic acid. Isolated MMA is primarily caused by the deficiency of methylmalonyl-CoA mutase (MMA mut; EC 5.4.99.2). A systematic literature review and a meta-analysis were undertaken to assess and compile published epidemiological data on MMA with a focus on the MMA mut subtype (OMIM #251000). Of the 1114 identified records, 227 papers were assessed for eligibility in full text, 48 articles reported on disease epidemiology, and 39 articles were included into the quantitative synthesis. Implementation of newborn screening in various countries has allowed for the estimation of birth prevalence of MMA and its isolated form. Meta-analysis pooled point estimates of MMA (all types) detection rates were 0.79, 1.12, 1.22 and 6.04 per 100,000 newborns in Asia-Pacific, Europe, North America and the Middle East and North Africa (MENA) regions, respectively. The detection rate of isolated MMA was < 1 per 100,000 newborns in all regions with the exception of MENA where it approached 6 per 100,000 newborns. Few studies published data on the epidemiology of MMA mut, therefore no meta-analysis could have been performed on this subtype. Most of the identified papers reported birth prevalence estimates below 1 per 100,000 newborns for MMA mut. The systematic literature review clearly demonstrates that MMA and its subtypes are ultra-rare disorders. Electronic supplementary material The online version of this article (10.1186/s13023-019-1063-z) contains supplementary material, which is available to authorized users.

BackgroundFunding of orphan medicinal products (OMPs) is an increasing challenge in the European Union (EU).ObjectivesTo identify the different methods for public funding of OMPs in order to map the availability for rare disease patients, as well as to compare the public expenditures on OMPs in 8 EU member states.MethodsInformation on the reimbursement status of 83 OMPs was collected in 8 countries by distinguishing standard and special reimbursements. In two consecutive years, the total public expenditures on OMPs were calculated by using annual EUR exchange rates. Annual total public expenditures were calculated per capita, and as a proportion of GDP, total public pharmaceutical and healthcare budgets. Differences between countries were compared by calculating the deviations from the average spending of countries.ResultsIn 2015 29.4–92.8% of the 83 OMPs were available with any kind of public reimbursement in participant countries including special reimbursement on an individual basis. In Austria, Belgium and France more OMPs were accessible for patients with public reimbursement than in Bulgaria, Czech Republic, Hungary and Poland. Standard reimbursement through retail pharmacies and/or hospitals was applied from 0 to 41% of OMPs. The average annual total public expenditure ranged between 1.4–23.5 €/capita in 2013 and 2014. Higher income countries spent more OMPs in absolute terms. Participant countries spent 0.018–0.066% of their GDPs on funding OMPs. Average expenditures on OMPs were ranged between 2.25–6.51% of the public pharmaceutical budget, and 0.44–0.96% of public healthcare expenditures.ConclusionsStandard and special reimbursement techniques play different roles in participant countries. The number of accessible OMPs indicated an equity gap between Eastern and Western Europe. The spending on OMPs as a proportion of GDP, public pharmaceutical and healthcare expenditure was not higher in lower income countries, which indicates substantial differences in patient access to OMPs in favour of higher-income countries. Equity in access for patients with rare diseases is an important policy objective in each member state of the EU; however, equity in access should be harmonized at the European level.Electronic supplementary materialThe online version of this article (10.1186/s13023-018-0927-y) contains supplementary material, which is available to authorized users.