title: The development of an objective methodology to measure medication adherence to oral thiopurines in paediatric patients with acute lymphoblastic leukaemia--an exploratory study.
abstract: OBJECTIVE
  To develop a method that prospectively assesses adherence rates in paediatric patients with acute lymphoblastic leukaemia (ALL) who are receiving the oral thiopurine treatment 6-mercaptopurine (6-MP).
  
  
  METHODS
  A total of 19 paediatric patients with ALL who were receiving 6-MP therapy were enrolled in this study. A new objective tool (hierarchical cluster analysis of drug metabolite concentrations) was explored as a novel approach to assess non-adherence to oral thiopurines, in combination with other objective measures (the pattern of variability in 6-thioguanine nucleotide erythrocyte concentrations and 6-thiouric acid plasma levels) and the subjective measure of self-reported adherence questionnaire.
  
  
  RESULTS
  Parents of five ALL patients (26.3%) reported at least one aspect of non-adherence, with the majority (80%) citing "carelessness at times about taking medication" as the primary reason for non-adherence followed by "forgetting to take the medication" (60%). Of these patients, three (15.8%) were considered non-adherent to medication according to the self-reported adherence questionnaire (scored > or = 2). Four ALL patients (21.1%) had metabolite profiles indicative of non-adherence (persistently low levels of metabolites and/or metabolite levels clustered variably with time). Out of these four patients, two (50%) admitted non-adherence to therapy. Overall, when both methods were combined, five patients (26.3%) were considered non-adherent to medication, with higher age representing a risk factor for non-adherence (P < 0.05).
  
  
  CONCLUSIONS
  The present study explored various ways to assess adherence rates to thiopurine medication in ALL patients and highlighted the importance of combining both objective and subjective measures as a better way to assess adherence to oral thiopurines.
authors.affiliation: Clinical and Practice Research Group, School of Pharmacy, Medical Biology Centre, Queen's University Belfast, 97 Lisburn Road, BT9 7BL, Belfast, UK.
authors.forename: Ahmed F
authors.initials: AF
authors.lastname: Hawwa
authors.forename: Jeff S
authors.initials: JS
authors.lastname: Millership
authors.forename: Paul S
authors.initials: PS
authors.lastname: Collier
authors.forename: Anthony
authors.initials: A
authors.lastname: McCarthy
authors.forename: Sid
authors.initials: S
authors.lastname: Dempsey
authors.forename: Carole
authors.initials: C
authors.lastname: Cairns
authors.forename: James C
authors.initials: JC
authors.lastname: McElnay
mesh_terms: D000293:Adolescent; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D055118:Medication Adherence; D015122:Mercaptopurine / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*; D010290:Parents; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D013866:Thioguanine / Q000097:blood; D014527:Uric Acid / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D000964:Antimetabolites, Antineoplastic; D014527:Uric Acid; C010352:6-thiouric acid; D015122:Mercaptopurine; D013866:Thioguanine