title: Determining the value of medical technologies to treat ultra-rare disorders: a consensus statement.
abstract: BACKGROUND
  In most jurisdictions, policies have been adopted to encourage the development of treatments for rare or orphan diseases. While successful as assessed against their primary objective, these policies have prompted concerns among payers about the economic burden that might be caused by an annual cost per patient in some cases exceeding 100,000 Euro. At the same time, many drugs for rare disorders do not meet conventional standards for cost-effectiveness or 'value for money'. Owing to the fixed (volume-independent) cost of research and development, this issue is becoming increasingly serious with decreasing prevalence of a given disorder.
  
  
  METHODS
  In order to critically appraise the problems posed by the systematic valuation of interventions for ultra-rare disorders (URDs), an international group of clinical and health economic experts was convened in conjunction with the Annual European ISPOR Congress in Berlin, Germany, in November 2012. Following this meeting and during subsequent deliberations, the group achieved a consensus on the specific challenges and potential ways forward.
  
  
  RESULTS
  The group concluded that the complexities of research and development for new treatments for URDs may require conditional approval and reimbursement policies, such as managed entry schemes and coverage with evidence development agreements, but should not use as justification surrogate end point improvement only. As a prerequisite for value assessment, the demonstration of a minimum significant clinical benefit should be expected within a reasonable time frame. As to the health economic evaluation of interventions for URDs, the currently prevailing logic of cost-effectiveness (using benchmarks for the maximum allowable incremental cost per quality-adjusted life year gained) was considered deficient as it does not capture well-established social preferences regarding health care resource allocation.
  
  
  CONCLUSIONS
  Modified approaches or alternative paradigms to establish the 'value for money' conferred by interventions for URDs should be developed with high priority.
authors.affiliation: Institute of Public Health, Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany; University of Applied Economic Sciences Ludwigshafen, Ludwigshafen, Germany; Institute for Innovation and Valuation in Health Care, Wiesbaden, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schlander
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Silvio
authors.initials: S
authors.lastname: Garattini
authors.affiliation: Interdisziplinäres Zentrum für Public Health, Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kolominsky-Rabas
authors.affiliation: School of Pharmacy, University of Oslo, Oslo, Norway.
authors.forename: Erik
authors.initials: E
authors.lastname: Nord
authors.affiliation: The Swedish Institute for Health Economics, Lund, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Persson
authors.affiliation: Department of Pharmacy, University of Groningen, Groningen, Netherlands; Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: Postma
authors.affiliation: Centre for Health Economics, Monash University, Clayton, Victoria, Australia.
authors.forename: Jeff
authors.initials: J
authors.lastname: Richardson
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit (KU) Leuven, Leuven, Belgium.
authors.forename: Steven
authors.initials: S
authors.lastname: Simoens
authors.affiliation: Health Innovation Technology Transfer (HITT), Barcelona, Spain.
authors.forename: Oriol
authors.initials: O
authors.lastname: de Solà-Morales
authors.affiliation: Tolley Health Economics Ltd, Buxton, Derbyshire, Great Britain.
authors.forename: Keith
authors.initials: K
authors.lastname: Tolley
authors.affiliation: Public Health Department - Research Unit EA 3279, Faculty of Medicine, Aix Marseille University, Marseille, France.
authors.forename: Mondher
authors.initials: M
authors.lastname: Toumi
keywords: cost-effectiveness; economic evaluation; health technology assessment; multicriteria decision making; orphan drugs; social cost value analysis