title: Can the EVIDEM Framework Tackle Issues Raised by Evaluating Treatments for Rare Diseases: Analysis of Issues and Policies, and Context-Specific Adaptation.
abstract: BACKGROUND
  The multiplicity of issues, including uncertainty and ethical dilemmas, and policies involved in appraising interventions for rare diseases suggests that multicriteria decision analysis (MCDA) based on a holistic definition of value is uniquely suited for this purpose. The objective of this study was to analyze and further develop a comprehensive MCDA framework (EVIDEM) to address rare disease issues and policies, while maintaining its applicability across disease areas.
  
  
  METHODS
  Specific issues and policies for rare diseases were identified through literature review. Ethical and methodological foundations of the EVIDEM framework v3.0 were systematically analyzed from the perspective of these issues, and policies and modifications of the framework were performed accordingly to ensure their integration.
  
  
  RESULTS
  Analysis showed that the framework integrates ethical dilemmas and issues inherent to appraising interventions for rare diseases but required further integration of specific aspects. Modification thus included the addition of subcriteria to further differentiate disease severity, disease-specific treatment outcomes, and economic consequences of interventions for rare diseases. Scoring scales were further developed to include negative scales for all comparative criteria. A methodology was established to incorporate context-specific population priorities and policies, such as those for rare diseases, into the quantitative part of the framework. This design allows making more explicit trade-offs between competing ethical positions of fairness (prioritization of those who are worst off), the goal of benefiting as many people as possible, the imperative to help, and wise use of knowledge and resources. It also allows addressing variability in institutional policies regarding prioritization of specific disease areas, in addition to existing uncertainty analysis available from EVIDEM.
  
  
  CONCLUSIONS
  The adapted framework measures value in its widest sense, while being responsive to rare disease issues and policies. It provides an operationalizable platform to integrate values, competing ethical dilemmas, and uncertainty in appraising healthcare interventions.
authors.affiliation: LASER Analytica, 1405 Transcanadienne, Suite 310, Montreal, QC, H9P 2V9, Canada. monika.wagner@la-ser.com.
authors.forename: Monika
authors.initials: M
authors.lastname: Wagner
authors.affiliation: LASER Analytica, 1405 Transcanadienne, Suite 310, Montreal, QC, H9P 2V9, Canada.
authors.forename: Hanane
authors.initials: H
authors.lastname: Khoury
authors.affiliation: LASER Analytica, New York, NY, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Willet
authors.affiliation: LASER Analytica, 1405 Transcanadienne, Suite 310, Montreal, QC, H9P 2V9, Canada.
authors.forename: Donna
authors.initials: D
authors.lastname: Rindress
authors.affiliation: LASER Analytica, 1405 Transcanadienne, Suite 310, Montreal, QC, H9P 2V9, Canada.|University of Montreal, School of Public Health, Montreal, QC, Canada.
authors.forename: Mireille
authors.initials: M
authors.lastname: Goetghebeur
mesh_terms: D003661:Decision Support Techniques; D026690:Ethics, Clinical; D006801:Humans; D035583:Rare Diseases / Q000175:diagnosis / Q000191:economics* / Q000628:therapy*; D012720:Severity of Illness Index; D016896:Treatment Outcome