title: Methods for integrating medication compliance and persistence in pharmacoeconomic evaluations.
abstract: OBJECTIVE
  Suboptimal compliance and failure to persist with drug treatments are important determinants of therapeutic nonresponse and are of potential economic significance. The present article aims to describe the methodologies that may be appropriate for integrating noncompliance and nonpersistence in economic evaluations.
  
  
  METHODS
  MEDLINE and NHS-EED were searched for economic evaluations published in the period between 1997 and 2005. Articles were included if they explored the dependence of cost-effectiveness results on varying levels of some form of compliance-related measure. The different methodologies used were reviewed and articles were appraised critically. Alternative methodological approaches are proposed, illustrated by an example of the impact of different persistence rates on a treatment's cost-effectiveness.
  
  
  RESULTS
  Ten articles were selected for inclusion. These were generally scant on detail relating to how compliance/persistence was assessed and what the impact was on health outcomes. The methods used included Markov models and decision analyses. Markov models allow for persistence to be included directly in the analysis, as patients transit during each cycle. Net-benefit regression models are well suited for analyzing prospective and retrospective studies where patient-level data are available, whereas discrete event simulations have the potential to offer more flexibility.
  
  
  CONCLUSIONS
  Compliance and/or persistence are not included routinely in pharmacoeconomic analyses, despite their potential impact. Where compliance and/or persistence are included, a lack of methodological rigor and consistency in definitions often limits the usefulness of the analyses. The analytical techniques discussed in this article should serve as a basis for developing guidelines on appropriate methodology.
authors.affiliation: Institute of Medical and Social Care Research, University of Wales, Bangor, Gwynedd, Wales, UK. d.a.hughes@bangor.ac.uk
authors.forename: Dyfrig
authors.initials: D
authors.lastname: Hughes
authors.forename: Warren
authors.initials: W
authors.lastname: Cowell
authors.forename: Tamas
authors.initials: T
authors.lastname: Koncz
authors.forename: Joyce
authors.initials: J
authors.lastname: Cramer
mesh_terms: D003362:Cost-Benefit Analysis / Q000706:statistics & numerical data; D003661:Decision Support Techniques; D004358:Drug Therapy / Q000191:economics*; D017850:Economics, Pharmaceutical / Q000706:statistics & numerical data*; D006801:Humans; D008390:Markov Chains; D017059:Models, Econometric; D010349:Patient Compliance; D012044:Regression Analysis