Efficacy of a medication management service in improving adherence to tyrosine kinase inhibitors and clinical outcomes of patients with chronic myeloid leukaemia: a randomised controlled trial

  • Bee Kim Tan
  • Siew Siang Chua
  • Li-Chia Chen
  • Kian Meng Chang
  • Sharmini Balashanker
  • Ping Chong BeeEmail author
Original Article



Suboptimal adherence to tyrosine kinase inhibitors (TKIs) contributes to poor clinical outcomes in chronic myeloid leukemia (CML). This randomised controlled trial (RCT) aimed to evaluate the impact of a medication management service (MMS) on adherence to TKIs and clinical outcomes.


A parallel RCT was conducted in two hospitals in Malaysia, where 129 CML patients were randomised to MMS or control (usual care) groups using a stratified 1:1 block randomisation method. The 6-month MMS included three face-to-face medication use reviews, CML and TKI-related education, two follow-up telephone conversations, a printed information booklet and two adherence aids. Medication adherence (primary outcome), molecular responses and health-related quality of life (HRQoL) scores were assessed at baseline, 6th and 12th month. Medication adherence and HRQoL were assessed using medication possession ratio and the European Organisation for Research and Treatment in Cancer questionnaire (EORTC_QLQ30_CML24) respectively.


The MMS group (n = 65) showed significantly higher adherence to TKIs than the control group (n = 64) at 6th month (81.5% vs 56.3%; p = 0.002), but not at 12th month (72.6% vs 60.3%; p = 0.147). In addition, a significantly higher proportion of participants in the MMS group achieved major molecular response at 6th month (58.5% vs 35.9%; p = 0.010), but not at 12th month (66.2% vs 51.6%; p = 0.092). Significant deep molecular response was also obtained at 12th month (24.6% vs 10.9%; p = 0.042). Six out of 20 subscales of EORTC-QLQ30-CML24 were significantly better in the MMS group.


The MMS improved CML patients’ adherence to TKI as well as achieved better clinical outcomes.

Trial Registration (ID: NCT03090477)


Medication management service Adherence Molecular response Health-related quality-of-life Chronic myeloid leukaemia Tyrosine kinase inhibitors 



The authors express their gratitude to all patients who have participated in the study. We would also like to record our appreciation to all the staff in the haematology clinics of the two hospitals in this study for their cooperation and assistance. We are grateful to Associate Professor Karuthan A/L Chinna from Taylor’s University Malaysia for his advice on statistical analysis, and to EORTC Quality of Life Group for permission granted to use the EORTC_QLQ30_CML24 questionnaire. We would also like to thank the Director General of Health Malaysia for his permission to publish this article.

Author contributions

Conceived and designed the study: BKT, SSC, PCB. Performed the study: BKT, SSC. Analysed the data: BKT, SSC, LCC, KMC, SB, PCB. Drafted the manuscript: BKT. Revised the manuscript critically for important intellectual content and approved the final version to be published: SSC, LCC, KMC, SB, PCB.

Funding information

This study received funding from the University of Malaya under a research grant (PG057-2015A).

Compliance with ethical standards

Ethical approvals for this study was obtained from the Medical Research and Ethics Committee (MREC) Ministry of Health Malaysia (Ref. No. NMRR-14-1466-23315 [IIR] dated 7 September 2015) and Medical Ethics Committee of University Malaya Medical Centre (Ref. No. 201411-802 dated 2 November 2014).

Conflict of interest

The authors declare that they have no conflicts of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Medicine, Faculty of MedicineUniversity of MalayaKuala LumpurMalaysia
  2. 2.School of Pharmacy, Faculty of Health and Medical SciencesTaylor’s UniversitySubang JayaMalaysia
  3. 3.Centre for Pharmacoepidemiology and Drug Safety, Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and HealthUniversity of Manchester, Manchester Academic Health Science CentreManchesterUK
  4. 4.Department of HematologyAmpang HospitalAmpangMalaysia
  5. 5.Ministry of Health MalaysiaPutrajayaMalaysia
  6. 6.School of PharmacyUniversity of Nottingham Malaysia CampusSemenyihMalaysia

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