title: Estimating time-varying drug adherence using electronic records: extending the proportion of days covered (PDC) method.
abstract: OBJECTIVE
  Accurate measurement of drug adherence is essential for valid risk-benefit assessments of pharmacologic interventions. To date, measures of drug adherence have almost exclusively been applied for a fixed-time interval and without considering changes over time. However, patients with irregular dosing behaviour commonly have a different prognosis than patients with stable dosing behaviour.
  
  
  METHODS
  We propose a method, based on the proportion of days covered (PDC) method, to measure time-varying drug adherence and drug dosage using electronic records. We compare a time-fixed PDC method with the time-varying PDC method through detailed examples and through summary statistics of 100 randomly selected patients on statin therapy.
  
  
  RESULTS
  We demonstrate that time-varying PDC method better distinguishes an irregularly dosing patient from a stably dosing patient and demonstrate how the time-fixed method can result in a biassed estimate of drug adherence. Furthermore, the time-varying PDC method may be better used to reduce certain types of confounding and misclassification of exposure.
  
  
  CONCLUSIONS
  The time-varying PDC method may improve longitudinal and time-to-event studies that associate adherence with a clinical outcome or (intervention) studies that seek to describe changes in adherence over time.
authors.affiliation: Unit PharmacoEpidemiology & PharmacoEconomics (PE2), Department of Pharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: Maarten J
authors.initials: MJ
authors.lastname: Bijlsma
authors.affiliation: Population Research Centre (PRC), Faculty of Spatial Sciences, University of Groningen, Groningen, The Netherlands.|Netherlands Interdisciplinary Demographic Institute, Hague, The Netherlands.
authors.forename: Fanny
authors.initials: F
authors.lastname: Janssen
authors.affiliation: Unit PharmacoEpidemiology & PharmacoEconomics (PE2), Department of Pharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: Eelko
authors.initials: E
authors.lastname: Hak
mesh_terms: D011307:Drug Prescriptions / Q000706:statistics & numerical data*; D057286:Electronic Health Records / Q000706:statistics & numerical data*; D055695:Electronic Prescribing / Q000706:statistics & numerical data*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D017891:Pharmacoepidemiology / Q000379:methods* / Q000706:statistics & numerical data; D013997:Time Factors; D016903:Drug Monitoring
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
keywords: adherence; longitudinal; methods; pharmacoepidemiology; time dependence