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Failure mode and effects analysis of medication adherence in patients with chronic myeloid leukemia



Poor adherence to ABL tyrosine kinase inhibitors (ABL TKIs) is associated with reduced treatment efficacy and increased healthcare costs. To examine the hazards associated with poor adherence, we implemented failure mode and effects analysis (FMEA).


We surveyed 54 chronic myeloid leukemia (CML) patients treated at Saga University Hospital from October 2012 to May 2014. The survey consisted of items regarding the type of ABL TKI used, adherence to ABL TKIs, the appearance of adverse effects, utilisation of the high cost medical care benefit system, and factors affecting adherence. Four factors that likely affected adherence were identified, including the level of understanding of ABL TKIs treatment outcomes, adverse effects, the high cost of medications, and careless slips in the taking of medicine. Results of the survey were analysed by FMEA.


The risk priority number was highest for careless slips in the taking of medicine at 7.0 ± 1.0 (mean ± SEM), followed in descending order by the inadequate understanding of treatment outcomes (4.9 ± 0.6), adverse effects (3.8 ± 0.8), and high medication cost (2.2 ± 0.5). Thus, the prevention of careless slips was the most important factor affecting adherence to ABL TKIs. Contrary to our preoccupation, FMEA revealed that high medication cost was the lowest risk factor for poor adherence. This finding may be attributed to the high utilisation (96.3 %) of the high cost medical care benefit system.


These findings suggest that an inadequate medication-taking habit such as careless slips may represent a potential target to improve and maximize adherence in CML patients.

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  1. Marin D, Bazeos A, Mahon FX et al (2010) Adherence is the critical factor for achieving molecular responses in patients with chronic myeloid leukemia who achieve complete cytogenetic responses on imatinib. J Clin Oncol 28:2381–2388

    CAS  Article  PubMed  Google Scholar 

  2. Noens L, van Lierde MA, De Bock R et al (2009) Prevalence, determinants, and outcomes of nonadherence to imatinib therapy in patients with chronic myeloid leukemia: the ADAGIO study. Blood 113:5401–5411

    CAS  Article  PubMed  Google Scholar 

  3. Wu EQ, Johnson S, Beaulieu N et al (2010) Healthcare resource utilization and costs associated with non-adherence to imatinib treatment in chronic myeloid leukemia patients. Curr Med Res Opin 26:61–69

    Article  PubMed  Google Scholar 

  4. Darkow T, Henk HJ, Thomas SK et al (2007) Treatment interruptions and non-adherence with imatinib and associated healthcare costs: a retrospective analysis among managed care patients with chronic myelogenous leukaemia. Pharmacoeconomics 25:481–496

    CAS  Article  PubMed  Google Scholar 

  5. Cramer JA, Roy A, Burrell A et al (2008) Medication compliance and persistence: terminology and definitions. Value Health 11:44–47

    Article  PubMed  Google Scholar 

  6. Efficace F, Rosti G, Cottone F et al (2014) Profiling chronic myeloid leukemia patients reporting intentional and unintentional non-adherence to lifelong therapy with tyrosine kinase inhibitors. Leuk Res 38:294–298

    Article  PubMed  Google Scholar 

  7. Eliasson L, Clifford S, Barber N et al (2011) Exploring chronic myeloid leukemia patients’ reasons for not adhering to the oral anticancer drug imatinib as prescribed. Leuk Res 35:626–630

    Article  PubMed  Google Scholar 

  8. Moon JH, Sohn SK, Kim SN et al (2012) Patient counseling program to improve the compliance to imatinib in chronic myeloid leukemia patients. Med Oncol 29:1179–1185

    Article  PubMed  Google Scholar 

  9. Kimura S (2010) Development of ABL tyrosine kinase inhibitors. Rinsho Ketsueki 51:597–604

    PubMed  Google Scholar 

  10. Drucker AM, Wu S, Busam KJ et al (2013) Rash with the multitargeted kinase inhibitors nilotinib and dasatinib: meta-analysis and clinical characterization. Eur J Haematol 90:142–150

    CAS  Article  PubMed  Google Scholar 

  11. Dusetzina SB, Winn AN, Abel GA et al (2014) Cost sharing and adherence to tyrosine kinase inhibitors for patients with chronic myeloid leukemia. J Clin Oncol 32:306–311

    Article  PubMed  Google Scholar 

  12. Neugut AI, Subar M, Wilde ET et al (2011) Association between prescription co-payment amount and compliance with adjuvant hormonal therapy in women with early-stage breast cancer. J Clin Oncol 29:2534–2542

    PubMed Central  Article  PubMed  Google Scholar 

  13. Hosoya K, Mochinaga S, Nakano Y et al (2012) Issues of molecular targeted drugs for chronic myeloid leukemia available in a community pharmacy. J Jpn Soc Hosp Pharm 48:1489–1492

    Google Scholar 

  14. Reason J (2000) Human error: models and management. BMJ 320:768–770

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  15. Mochinaga S, Matsunaga H, Emoto A et al (2006) Application of failure modes and effect analysis in prevention of medication errors in cancer chemotherapy. Jpn J Pharm Health Care Sci 32:1050–1058

    Article  Google Scholar 

  16. Weingart SN, Spencer J, Buia S et al (2011) Medication safety of five oral chemotherapies: a proactive risk assessment. J Oncol Pract 7:2–6

    PubMed Central  Article  PubMed  Google Scholar 

  17. Lago P, Bizzarri G, Scalzotto F et al (2012) Use of FMEA analysis to reduce risk of errors in prescribing and administering drugs in paediatric wards: a quality improvement report. BMJ Open. doi:10.1136/bmjopen-2012-001249

    PubMed Central  PubMed  Google Scholar 

  18. Walsh KE, Mazor KM, Roblin D et al (2013) Multisite parent-centered risk assessment to reduce pediatric oral chemotherapy errors. J Oncol Pract. doi:10.1200/JOP.2012.000601

    Google Scholar 

  19. Sumi M, Tauchi T, Sashida G et al (2005) Clinical usefulness of transcription-mediated amplification and hybridization protection assay in imatinib-treated chronic myelogenous leukemia patients. Clin Lab Haematol 27:416–417

    CAS  Article  PubMed  Google Scholar 

  20. Yagasaki F, Niwa T, Abe A et al (2009) Correlation of quantification of major bcr-abl mRNA between TMA (transcription mediated amplification) method and real-time quantitative PCR. Rinsho Ketsueki 50:481–487

    PubMed  Google Scholar 

  21. Latino RJ, Flood A (2004) Optimizing FMEA and RCA efforts in health care. J Healthc Risk Manag 24:21–28

    Article  PubMed  Google Scholar 

  22. Mahon FX, Réa D, Guilhot J et al (2010) Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol 11:1029–1035

    CAS  Article  PubMed  Google Scholar 

  23. Clifford S, Barber N, Elliott R et al (2006) Patient-centred advice is effective in improving adherence to medicines. Pharm World Sci 28:165–170

    Article  PubMed  Google Scholar 

  24. Zedler BK, Joyce A, Murrelle L et al (2011) A pharmacoepidemiologic analysis of the impact of calendar packaging on adherence to self-administered medications for long-term use. Clin Ther 33:581–597

    Article  PubMed  Google Scholar 

  25. Vervloet M, van Dijk L, de Bakker DH et al (2014) Short- and long-term effects of real-time medication monitoring with short message service (SMS) reminders for missed doses on the refill adherence of people with Type 2 diabetes: evidence from a randomized controlled trial. Diabet Med 31:821–828

    CAS  Article  PubMed  Google Scholar 

  26. Montes JM, Medina E, Gomez-Beneyto M et al (2012) A short message service (SMS)-based strategy for enhancing adherence to antipsychotic medication in schizophrenia. Psychiatry Res 200:89–95

    Article  PubMed  Google Scholar 

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Conflict of interest

The authors declare that they except S.K. have no conflict of interest. S.K. has received research funding and honoraria from Bristol-Myers Squibb and Novartis.

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Correspondence to Shinya Kimura.

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K. Hosoya and S. Mochinaga contributed equal to the manuscript.

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Hosoya, K., Mochinaga, S., Emoto, A. et al. Failure mode and effects analysis of medication adherence in patients with chronic myeloid leukemia. Int J Clin Oncol 20, 1203–1210 (2015).

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  • Chronic myeloid leukemia
  • Failure mode and effects analysis
  • Adherence
  • ABL tyrosine kinase inhibitor