title: Investigating the association between medication adherence and health-related quality of life in COPD: Methodological challenges when using a proxy measure of adherence.
abstract: BACKGROUND
  The association between non-adherence to medication and health-related quality-of-life (HRQoL) in Chronic Obstructive Pulmonary Disease (COPD) remains poorly understood. Different ways to deal with methodological challenges to estimate this association have probably contributed to conflicting results.
  
  
  OBJECTIVE
  To investigate the association between medication adherence and HRQoL, thereby illustrating methodological challenges that need to be addressed.
  
  
  METHODS
  We used longitudinal patient-level data from a cluster-randomized controlled trial (i.e. RECODE) including three-year data on type and dose of COPD maintenance medication prescribed and HRQoL (Clinical COPD Questionnaire [CCQ], st. George Respiratory Questionnaire [SGRQ], EuroQol 5-dimensions [EQ-5D]) of 511 patients. A linear mixed model was used to assess the association between adherence and HRQoL using a fixed cut-off of 80% of the proportion of days covered (PDC) to define adherence. Subsequently, we investigated the impact of differences in disease severity; lifestyle; and reversed causality, representing the methodological challenges. Additionally, we investigated the impact of changing the definition of adherence.
  
  
  RESULTS
  In unadjusted analyses, and analyses adjusting for demographic characteristics only, SGRQ score was worse in the adherent compared to the non-adherent group. This association disappeared when correcting for disease severity and/or lifestyle. A better SGRQ score was predictive of decreased adherence in the following year. However, accounting for the previous HRQoL did not result in positive associations between adherence and HRQoL. When defining four categories of adherence, patients with a PDC between 80 and 99% had a significantly worse SGRQ score compared to patients with a PDC <60%, even after correction for lifestyle. There was no significant association between adherence and CCQ or EQ-5D.
  
  
  CONCLUSIONS
  This study showed persistent methodological challenges in the investigation of the effect of medication adherence on HRQoL in COPD. A positive association of adherence and HRQoL was not found, even after adjusting for lifestyle, disease severity, and previous HRQoL.
authors.affiliation: Institute for Medical Technology Assessment, Institute of Health Policy and Management, Erasmus University, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. Electronic address: boland@bmg.eur.nl.
authors.forename: Melinde R S
authors.initials: MR
authors.lastname: Boland
authors.affiliation: Unit of PharmacoEpidemiology & PharmacoEconomics, Department of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors.forename: Job F M
authors.initials: JF
authors.lastname: van Boven
authors.affiliation: Department of Public Health and Primary Care, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: Annemarije L
authors.initials: AL
authors.lastname: Kruis
authors.affiliation: Department of Public Health and Primary Care, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: Niels H
authors.initials: NH
authors.lastname: Chavannes
authors.affiliation: Department of General Practice, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands.
authors.forename: Thys
authors.initials: T
authors.lastname: van der Molen
authors.affiliation: Institute for Medical Technology Assessment, Institute of Health Policy and Management, Erasmus University, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands.
authors.forename: Lucas M A
authors.initials: LM
authors.lastname: Goossens
authors.affiliation: Institute for Medical Technology Assessment, Institute of Health Policy and Management, Erasmus University, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands.
authors.forename: Maureen P M H
authors.initials: MP
authors.lastname: Rutten-van Mölken
mesh_terms: D000368:Aged; D005260:Female; D006304:Health Status; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D016903:Drug Monitoring
keywords: Adherence; Chronic obstructive pulmonary disease; Maintenance medication; Prescription; Proxy; Quality-of-life