title: Rare Disease Terminology and Definitions-A Systematic Global Review: Report of the ISPOR Rare Disease Special Interest Group.
abstract: BACKGROUND
  At present, there is no universal definition of rare disease.
  
  
  OBJECTIVE
  To provide an overview of rare disease definitions currently used globally.
  
  
  METHODS
  We systematically searched for definitions related to rare disease from organizations in 32 international jurisdictions. Descriptive statistics of definitions were generated and prevalence thresholds were calculated.
  
  
  RESULTS
  We identified 296 definitions from 1109 organizations. The terms "rare disease(s)" and "orphan drug(s)" were used most frequently (38% and 27% of the definitions, respectively). Qualitative descriptors such as "life-threatening" were used infrequently. A prevalence threshold was specified in at least one definition in 88% of the jurisdictions. The average prevalence threshold across organizations within individual jurisdictions ranged from 5 to 76 cases/100,000 people. Most jurisdictions (66%) had an average prevalence threshold between 40 and 50 cases/100,000 people, with a global average of 40 cases/100,000 people. Prevalence thresholds used by different organizations within individual jurisdictions varied substantially. Across jurisdictions, umbrella patient organizations had the highest (most liberal) average prevalence threshold (47 cases/100,000 people), whereas private payers had the lowest threshold (18 cases/100,000 people).
  
  
  CONCLUSIONS
  Despite variation in the terminology and prevalence thresholds used to define rare diseases among different jurisdictions and organizations, the terms "rare disease" and "orphan drug" are used most widely and the average prevalence threshold is between 40 and 50 cases/100,000 people. These findings highlight the existing diversity among definitions of rare diseases, but suggest that any attempts to harmonize rare disease definitions should focus on standardizing objective criteria such as prevalence thresholds and avoid qualitative descriptors.
authors.affiliation: Canadian Agency for Drugs & Technologies in Health (CADTH), Ottawa, Ontario, Canada. Electronic address: trevorr@cadth.ca.
authors.forename: Trevor
authors.initials: T
authors.lastname: Richter
authors.affiliation: Roboleo & Co, York, UK.
authors.forename: Sandra
authors.initials: S
authors.lastname: Nestler-Parr
authors.affiliation: St. Elizabeth University, Bratislava, Slovakia.
authors.forename: Robert
authors.initials: R
authors.lastname: Babela
authors.affiliation: Celgene Corporation, Summit, NJ, USA.
authors.forename: Zeba M
authors.initials: ZM
authors.lastname: Khan
authors.affiliation: International Society for Pharmacoeconomics and Outcomes Research (ISPOR), South Lawrenceville, NJ, USA.
authors.forename: Theresa
authors.initials: T
authors.lastname: Tesoro
authors.affiliation: International Society for Pharmacoeconomics and Outcomes Research (ISPOR), South Lawrenceville, NJ, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Molsen
authors.affiliation: Center for Health Economics and Medicines Evaluation, Bangor University, Wales, UK.
authors.forename: Dyfrig A
authors.initials: DA
authors.lastname: Hughes
mesh_terms: D006801:Humans; D032921:Consensus; D014943:Global Health / Q000145:classification; D009965:Orphan Drug Production / Q000145:classification; D015995:Prevalence; D011379:Prognosis; D035583:Rare Diseases / Q000145:classification / Q000175:diagnosis / Q000453:epidemiology / Q000628:therapy; D018570:Risk Assessment; D012307:Risk Factors; D009626:Terminology as Topic
keywords: orphan drugs; prevalence; rare disease; terminology