European Journal of Clinical Pharmacology

, Volume 65, Issue 11, pp 1105–1112 | Cite as

The development of an objective methodology to measure medication adherence to oral thiopurines in paediatric patients with acute lymphoblastic leukaemia—an exploratory study

  • Ahmed F. Hawwa
  • Jeff S. Millership
  • Paul S. Collier
  • Anthony McCarthy
  • Sid Dempsey
  • Carole Cairns
  • James C. McElnayEmail author
Pharmacokinetics and Disposition



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).


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.


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 ≥ 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).


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.


Thiopurines 6-mercaptopurine Paediatrics Acute lymphoblastic leukaemia Medication adherence 


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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Ahmed F. Hawwa
    • 1
  • Jeff S. Millership
    • 1
  • Paul S. Collier
    • 1
  • Anthony McCarthy
    • 2
  • Sid Dempsey
    • 2
  • Carole Cairns
    • 2
  • James C. McElnay
    • 1
    Email author
  1. 1.Clinical and Practice Research Group, School of Pharmacy, Medical Biology CentreQueen’s University BelfastBelfastUK
  2. 2.Haematology and Oncology Outpatient Department, Royal Belfast Hospital for Sick ChildrenThe Royal Hospitals, Belfast Health and Social Care TrustBelfastUK

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