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Background Funding of orphan medicinal products (OMPs) is an increasing challenge in the European Union (EU). Objectives To 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. Methods Information 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. Results In 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. Conclusions Standard 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 material The online version of this article (10.1186/s13023-018-0927-y) contains supplementary material, which is available to authorized users.

Rare diseases are often serious, chronic and life-threatening. The European Union (EU) definition of a rare disease is one that affects fewer than 5 in 10 000 people. (1) At present, more than 6000 rare diseases are known; around 80% of them are genetic disorders and half of them occur during childhood. Grouped together, rare diseases affect 6-8% (or about 30 million people) out of the 508 million population of EU countries. (2) This roughly equals the estimated prevalence of diabetes in the World Health Organization European Region, which in 2013 was 6.8% of 658.7 million adults in the 20-79 year age group. (3) This illustrates the paradox of rarity: each disease is rare but collectively, rare diseases affect many people. (4) In 2009, responding to increasing concerns about the issue, the European Council published a recommendation (2009/C 151/02) on action in the field of rare diseases, recommending Member States to adopt and establish national plans for rare diseases by the end of 2013. (2) Rare diseases are associated with a high psychological burden for the patient but they can also have a major impact on a patient's family. (5) In addition to the health burden on patients, few of these diseases have an effective drug treatment available. This is because the drugs to treat rare diseases (called orphan drugs) are not commercially viable for pharmaceutical companies, due to the small number of patients per disease. To encourage pharmaceutical companies to develop and market orphan drugs, the European Parliament and the European Council published the regulation (EC) No 141/2000 on orphan medicinal products in 1999. (1) Orphan designation for a medicine is granted at the European level by the European Medicines Agency (EMA). Three criteria must be met, as stated in the regulation: "(i) the medicine must be intended for the treatment, prevention or diagnosis of a disease that is life-threatening or chronically debilitating; (ii) the prevalence of the condition in the European Union must be no more than 5 in 10 000 or it must be unlikely that the marketing of the medicine would generate sufficient returns to justify the investment needed for its development; and (iii) no satisfactory method of diagnosis, prevention or treatment of the condition concerned can be authorized, or, if such a method exists, the medicine must be of significant benefit to those affected by the condition". (1) The application for orphan designation, which can be submitted by the sponsor of the medicinal product at any stage of drug development, is then examined within 90 days by the Committee for Orphan Medicinal Products of the EMA. When a medicine is granted orphan designation, several incentives are provided to the sponsor of a clinical trial, as stated in regulation (EC) No 141/2000. (1) These incentives include protocol assistance, scientific advice from EMA before the submission for marketing authorization and market exclusivity of 10 years once the medicine is marketed. This period of market exclusivity can be extended by two years for medicines that comply with an agreed investigation plan for medicines for paediatric care. Finally, depending on the status of the sponsor and the type of service required, reductions in fees to be paid for regulatory activities related to the evaluation of orphan medicinal products by EMA (e.g. protocol assistance, application for marketing authorization) can also be available for the sponsor. By the end of 2015, 89 different orphan medicinal products had received authorization to enter the market from the EMA's Committee for Medicinal Products for Human Use, and 123 other medicinal products intended for rare diseases but without the orphan designation in Europe also received the European marketing authorization. (6) In addition, an increasing number of applications for orphan designation are submitted to EMA each year (Fig. 1). (7) As a consequence, an increasing number of applications for a marketing authorization of an orphan medicinal product is observed each year. …

INTRODUCTION:We test in practice a Multiple Criteria Decision Analysis (MCDA) framework for the value assessment of a set of therapeutic options for the indication of hormone relapsed metastatic prostate cancer (mPC) through a series of simulation exercises with the participation of decision makers from different Health Technology Assessment (HTA)/insurance agencies across Europe, including TLV (Sweden), AETSA (Andalusia-Spain), INAMI-RIZIV (Belgium) and AOTMiT (Poland). The drugs evaluated were abiraterone, cabazitaxel and enzalutamide.METHODS:Using a multi-attribute value theory framework, past research outcomes and literature findings, an mPC-specific value tree was constructed incorporating relevant concerns as criteria. By adopting the MACBETH approach the different drugs were scored against the criteria through the development of value functions, relative weights were assigned to the criteria using a swing weighting technique, scores and weights were combined using an additive aggregation technique, and sensitivity analysis of results was conducted. All stages were informed through the participation of a small group of experts from each HTA/insurance agency at a series of decision conferences taking place in each country.RESULTS:Value parameters considered spanned the dimensions of therapeutic impact, safety profile, innovation level and socioeconomic impact. Overall weighted preference value scores were produced reflecting the performance of the treatments against the criteria while considering their relative importance. Order of treatments’ rankings was identical across all agencies, with enzalutamide scoring highest and cabazitaxel lowest. Therapeutic impact criteria always produced the greatest relative weight. Hypothetical priority setting decisions were made based on “value-for-money” grounds through the use of “cost per unit of value” metrics by incorporating purchasing costs.CONCLUSIONS:The MCDA framework tested possesses a number of characteristics that could facilitate decision making, including the systematic and explicit incorporation of value trade-offs as part of model assessment and the transparency throughout all its stages. Therefore, it has the prospects to act as a practical evaluation tool for value assessment and communication during the HTA process.

The goal of health care policies is to maximize the health of the population within the limits of the available budget and taking into account equity considerations. For innovative drugs, this means that an increasing number are being assessed in terms of their value for money, which is the amount of additional health that can be achieved per additional euro, pound, dollar, or other currency invested. Ideally such assessments and resulting appraisals and decisions should be made in a transparent and efficient way. Transparent means consisting of clear procedures and criteria such as relative effectiveness, cost effectiveness, budget impact, social, and ethical consequences. Transparent also means that stakeholders (physicians, patients, industry, and others) are involved in the assessment and decision-making process. Efficient means that, on a European level, duplication of efforts is avoided by aligning the processes for market authorization and those for the assessment of value for money. Drug Dev Res 71: 457–462, 2010. © 2010 Wiley-Liss, Inc.

Context Although the EU Council stated[1] that “All health systems in the EU aim to make provision, which is patient-centered and responsive to individual need”, numerous sources show important and unacceptable differences in access to orphan drugs in the Member States of the European Union (EU COM [2], EURORDIS [3,4], BE EU Presidency [5,8], EU Council [6]). With this regard, in the context of the 2010 Belgian EU presidency initiative on ‘Innovation and Solidarity’ and within the framework of the process on corporate responsibility in the field of pharmaceuticals [7], EU Commissioner Tajani launched the project Mechanism of Coordinated Access to Orphan Drugs.

Background National payers across Europe have been increasingly looking into innovative reimbursement approaches – called managed entry agreements (MEAs) – to balance the need to provide rapid access to potentially beneficial orphan medicinal products (OMPs) with the requirements to circumscribe uncertainty, obtain best value for money or to ensure affordability. This study aimed to identify, describe and classify MEAs applied to OMPs by national payers and to analyse their practice in Europe. Methods To identify and describe MEAs, national health technology assessments and reimbursement decisions on OMPs across seven European countries were reviewed and their main characteristics extracted. To fill data gaps and validate the accuracy of the extraction, collaboration was sought from national payers. To classify MEAs, a bespoke taxonomy was implemented. Identified MEAs were analysed and compared by focusing on five key themes, namely by describing the MEAs in relation to: drug targets and therapeutic classes, geographical spread, type of MEA applied, declared rationale for setting-up of MEAs, and evolution over time. Results 42 MEAs for 26 OMPs, implemented between 2006 and 2012 and representing a variety of MEA designs, were identified. Italy was the country with the highest number of schemes (n=15), followed by the Netherlands (n=10), England and Wales (n=8), Sweden (n=5) and Belgium (n=4). No MEA was identified for France and Germany due to data unavailability. Antineoplastic agents were the primary targets of MEAs. 55% of the identified MEAs were performance-based risk-sharing arrangements; the other 45% were financial-based. Nine of these 26 OMPs were subject to MEAs in two or three different countries, resulting in 24 MEAs. 60% of identified MEAs focused on conditions whose prevalence is less than 1 per 10,000. Conclusions This study confirmed that a variety of MEAs were increasingly used by European payers to manage aspects of uncertainty associated with the introduction of OMPs in the healthcare system, and which may be of a clinical, utilisation, or budgetary nature. It remains unclear whether differences in the use of MEAs reflect differences in how ‘uncertainty’ and ‘value’ are perceived across healthcare systems.

In the context of pharmaceutical care, policy-makers repeatedly face the challenge of balancing patient access to effective medicines with affordability and rising costs. With the aim of guiding the health policy discourse towards questions that are important to actual and potential patients, this study investigates a broad range of regulatory measures, spanning marketing authorization to generic substitution and resulting price levels in a sample of 16 European health systems (Austria, Belgium, Denmark, England, Finland, France, Germany, Greece, Ireland, Italy, the Netherlands, Poland, Portugal, Scotland, Spain and Sweden). All countries employ a mix of regulatory mechanisms to contain pharmaceutical expenditure and ensure quality and efficiency in pharmaceutical care, albeit with varying configurations and rigour. This variation also influences the extent of publicly financed pharmaceutical costs. Overall, observed differences in pharmaceutical expenditure should be interpreted in conjunction with the differing volume and composition of consumption and price levels, as well as dispensation practices and their impact on measurement of pharmaceutical costs. No definitive evidence has yet been produced on the effects of different cost-containment measures on patient outcomes. Depending on the foremost policy concerns in each country, different levers will have to be used to enable the delivery of appropriate care at affordable prices.

THE BELGIAN REIMBURSEMENT PROCEDURE (BRP):ARE ADDEDTHERAPEUTICVALUE (ATV) AND ICER AFFECTING THE DRUG REIMBURSEMENT DECISION (DRD)? Verplanken P,Arickx F, Bormans V, Soete E,Annemans L, Robays H,VanWilder P RIZIV-INAMI National Health Insurance Agency, Brussels, Belgium, University of Ghent, Brussels University, Ghent, Belgium, Ghent University, Grimbergen, Belgium OBJECTIVES: Since 2002, the BRP for medicinal products claiming ATV requires the evaluation of the therapeutic and pharmaco-economic value as compared to alternatives. The study aim was to analyze the effect of ATV and ICER on the DRD.METHODS: The RIZIV administrative database was used for extracting all files claiming ATV submitted between January 2002 and February 2008. ICERs expressed per QALY or per LYG were pooled. ATV was a binary outcome variable (ATV either present or absent). The DRD was either positive or negative. Statistical analysis (logistic regression /backwards elimination) was performed using SAS EG. The significance level was set at 0.05. Only complete cases were analyzed. RESULTS: A total of 138 submissions fulfilled the criteria. Data were available for all variables in only 76 (55.1%) cases. ATV and ICER were both significantly (p 0.10). CONCLUSIONS: Based on this sample, our analysis indicates that both ATV and ICER have a prognostic (but opposite) effect on the final DRD in Belgium. Further investigation should consider the potential effects of other variables such as budget impact, disease category, price and others on the DRD.