Dataset Information

Comparing access to orphan medicinal products in Europe.

ABSTRACT:

Objectives

The primary objective of this study was to compare the availability and access of orphan medicinal products (OMPs) in the devolved nations in the United Kingdom (UK), France, Germany, Italy and Spain. Availability is defined as the possibility to prescribe OMPs. Access refers to their full or partial reimbursement by the public health service.

Methods

Data were collated on: marketing authorisations, Health Technology Assessment (HTA) decisions, commissioning, and reimbursement decisions, and respective dates of these events for all the OMPs centrally authorised. Indicators of availability of and access to OMPs were calculated in each country and compared.

Results

We found that since the implementation of the OMPs Regulation in 2000 to end of May 2016, 143 OMPs obtained a marketing authorisation in the European Union. These OMPs are most widely accessible in Germany and France. In the other countries between 30 and 60% of OMPs are reimbursed. In particular in England, less than 50% of centrally authorised OMPs are routinely funded by the NHS, with one-third of these recommended by NICE. In Germany reimbursement is automatically granted to all medicines which receive a marketing authorisation, immediately after authorisation - but since 2011, there is an evaluation and potentially a pricing negotiation between companies and sickness funds (third party payers). In the other countries, the shortest time from authorisation to a reimbursement decision is observed in Italy and France where it takes 18.6 and 19.5 months respectively on average.

Conclusions

Marketing authorisation granted to OMPs is only the first step, as medicines reach patients when reimbursement decisions are implemented by national health systems (this applies to non-OMPs too). We found that more than a half of centrally authorised OMPs were available in the five selected countries, but that access to patients was further restricted by different national reimbursement policies, especially in the UK, Italy and Spain.

SUBMITTER: Zamora B

PROVIDER: S-EPMC6499954 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundTo assess uncertainty in regulatory decision-making for orphan medicinal products (OMP), a summary of the current basis for approval is required; a systematic grouping of medical conditions may be useful in summarizing information and issuing recommendations for practice.MethodsA grouping of medical conditions with similar characteristics regarding the potential applicability of methods and designs was created using a consensus approach. The 125 dossiers for authorised OMP published between 1999 and 2014 on the EMA webpage were grouped accordingly and data was extracted from European Public Assessment Reports (EPARs) to assess the extent and robustness of the pivotal evidence supporting regulatory decisions.Results88% (110/125) of OMP authorizations were based on clinical trials, with 35% (38/110) including replicated pivotal trials. The mean (SD) number of pivotal trials per indication was 1.4 (0.7), and the EPARs included a median of three additional non-pivotal supportive studies. 10% of OMPs (13/125) were authorised despite only negative pivotal trials. One-third of trials (53/159) did not include a control arm, one-third (50/159) did not use randomisation, half the trials (75/159) were open-label and 75% (119/159) used intermediate or surrogate variables as the main outcome. Chronic progressive conditions led by multiple system/organs, conditions with single acute episodes and progressive conditions led by one organ/system were the groups where the evidence deviated most from conventional standards. Conditions with recurrent acute episodes had the most robust datasets. The overall size of the exposed population at the time of authorisation of OMP?-?mean(SD) 190.5 (202.5)?-?was lower than that required for the qualification of clinically-relevant adverse reactions.ConclusionsThe regulatory evidence supporting OMP authorization showed substantial uncertainties, including weak protection against errors, substantial use of designs unsuited for conclusions on causality, use of intermediate variables, lack of a priorism and insufficient safety data to quantify risks of relevant magnitude. Grouping medical conditions based on clinical features and their methodological requirements may facilitate specific methodological and regulatory recommendations for the study of OMP to strengthen the evidence base.

Project description: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.

Project description:The research and development process in the field of rare diseases is characterised by many well-known difficulties, and a large percentage of orphan medicinal products do not reach the marketing approval.This work aims at identifying orphan medicinal products that failed the developmental process and investigating reasons for and possible factors influencing failures.Drugs designated in Europe under Regulation (European Commission) 141/2000 in the period 2000-2012 were investigated in terms of the following failures: (1) marketing authorisation failures (refused or withdrawn) and (2) drugs abandoned by sponsors during development.Possible risk factors for failure were analysed using statistically validated methods.This study points out that 437 out of 788 designations are still under development, while 219 failed the developmental process. Among the latter, 34 failed the marketing authorisation process and 185 were abandoned during the developmental process. In the first group of drugs (marketing authorisation failures), 50% reached phase II, 47% reached phase III and 3% reached phase I, while in the second group (abandoned drugs), the majority of orphan medicinal products apparently never started the development process, since no data on 48.1% of them were published and the 3.2% did not progress beyond the non-clinical stage.The reasons for failures of marketing authorisation were: efficacy/safety issues (26), insufficient data (12), quality issues (7), regulatory issues on trials (4) and commercial reasons (1). The main causes for abandoned drugs were efficacy/safety issues (reported in 54 cases), inactive companies (25.4%), change of company strategy (8.1%) and drug competition (10.8%). No information concerning reasons for failure was available for 23.2% of the analysed products.This analysis shows that failures occurred in 27.8% of all designations granted in Europe, the main reasons being safety and efficacy issues. Moreover, the stage of development reached by drugs represents a specific risk factor for failures.

Project description:BackgroundNational 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.MethodsTo 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.Results42 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.ConclusionsThis 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.

Project description:Background: Despite calls for the use of real-world data, the rare diseases (RD) treatment landscape suffers from a scarcity of data referred to orphan medicinal products (OMP) use at the population level. Objectives: We aim to describe the characteristics and patterns of utilization of OMP in a sizable group of RD patients globally monitored by an area-based rare diseases registry located in the Veneto region, Italy, during a 3-year period (1 January 2019 to 31 December 2021). Methods: A list of OMP (n = 60) was assembled for study purposes, according to extensive criteria with regard to the status of orphan designation and of national reimbursement decisions. Results: OMP prescriptions involved 1,010 patients, corresponding to the 2.3% of all the patients monitored by the RD registry. Nearly one out of five (22.8%) was a pediatric patient at the time of the first prescription. OMP use interested a limited proportion (17.5%) of diseases approaching the rarity threshold, having a prevalence of less than five per 10,000, while individuals affected by these more common rare conditions represented 49% of all the patients receiving an OMP prescription. A clustering effect of OMP use was observed in selected groups of diseases, mainly, neurological, hematological, and hereditary metabolic ones. Medication plans including an OMP show in the 45.9% of the cases a high level of complexity, both in terms of nature and number of co-prescribed treatments. Off-label use interested 15.3% (n = 155) of all the RD patients with at least an OMP prescription during the study period. Conclusion: Data collected in a real-world setting through population-based registries globally monitoring RD patients, including related medication plans, have the potential to identify which diseases, and thus patients, have less benefit from the advent of OMP so far. Furthermore, in the rapidly evolving RD therapeutic landscape, they can help understand which therapeutic areas are most in need of investment to address existing unmet care needs.