title: Reconciling uncertainty of costs and outcomes with the need for access to orphan medicinal products: a comparative study of managed entry agreements across seven European countries.
abstract: 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.
authors.affiliation: KU Leuven Department of Pharmaceutical and Pharmacological Sciences, O&N2 bus 521, Herestraat 49, Leuven, Belgium. thomas.morel@pharm.kuleuven.be.
authors.forename: Thomas
authors.initials: T
authors.lastname: Morel
authors.forename: Francis
authors.initials: F
authors.lastname: Arickx
authors.forename: Gustaf
authors.initials: G
authors.lastname: Befrits
authors.forename: Paolo
authors.initials: P
authors.lastname: Siviero
authors.forename: Caroline
authors.initials: C
authors.lastname: van der Meijden
authors.forename: Entela
authors.initials: E
authors.lastname: Xoxi
authors.forename: Steven
authors.initials: S
authors.lastname: Simoens
mesh_terms: D003362:Cost-Benefit Analysis; D005060:Europe; D006801:Humans; D007349:Insurance, Health, Reimbursement / Q000706:statistics & numerical data*; D009965:Orphan Drug Production / Q000191:economics*