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Published on 23 November 2012

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Improving adherence to oral cancer treatments

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Lina Eliasson PhD
Christina Jackson MSc PhD
Roseanna Brady MA MSc
Judith Kalthoff DClinPsych
Atlantis Research Institute, 
London, UK
Understanding the drivers and barriers of adherence to oral cancer treatment has become a key concern for all stakeholders, including patients, healthcare professionals, the pharmaceutical industry and governments.
Cancer is one of the leading threats to physical health and well-being worldwide. The yearly incidence is rising across most cancers, and at the same time age-specific death rates are decreasing because of new, effective treatments and earlier diagnosis. This means that there is a steady increase in the number of cancer patients and cancer survivors living in the community who have to manage their treatments long-term.
Traditionally, cancer has been treated with injected chemotherapy, radiotherapy and surgery delivered in a supervised clinical setting. The increasing use of oral formulations, which are often preferred by patients, has changed this paradigm, and today a large number of patients are expected to self-manage their treatment regimen at home. This brings with it a number of benefits for the patients and healthcare providers (HCPs) but also many challenges.
The benefits for the patients include increased autonomy, less time spent at the hospital and less intrusive interventions. For HCPs, the costs related to inpatient stays are reduced and more time is freed up for staff. The challenges for HCPs are to provide patients with the knowledge and, as far as possible, support their ability to take their medication as prescribed. The challenge as an outpatient, by contrast, is to incorporate the treatment regimen into day-to-day life and to take responsibility for managing all aspects of the regimen. Treatment adherence, defined as patients taking their medication as prescribed by their physician, has therefore received increased attention in the field of oncology and it has been recognised that cancer patients prescribed oral medicines might need additional support to maintain optimal adherence levels.
Extent and impact of non-adherence
In reality, it is common that cancer patients miss doses of their treatment regimen and there is an average non-adherence rate of approximately 20%.(1) However, broad variations of up to 84% non-adherence has been reported, which in part depends on the definitions and measurements used.(2) In addition, non-adherence to maintenance therapy has been shown to increase with time in, for example, breast cancer.(3)
The consequences of non-adherence to anticancer medicines are serious.(2) For example, non-adherence by taking less medication than prescribed can result in faster illness progression, as well as avoidable morbidity and mortality. In contrast, non-adherence through over-dosing can also lead to hospitalisation and death caused by drug toxicity. In addition, non-adherence during clinical trials may lead to biased results and erroneous conclusions of drug effects.
There are also economic consequences of non-adherence. For example, non-adherence to imatinib (Gleevec/Glivec®; Novartis) in chronic myeloid leukaemia patients has been shown to increase healthcare costs.(4) This US study investigated associations between non-adherence, patient characteristics and healthcare costs and used medication possession ratio (MPR) as a proxy measure of adherence (calculated as days covered by cashed prescriptions divided by days prescribed). Thirty-one percent of patients were identified as having treatment interruptions of at least 30 consecutive days and reduced MPR was related to increased healthcare and medical costs.(4)
Why are patients non-adherent?
To develop interventions to help cancer patients to adhere optimally to their treatment, we need to improve our understanding of why cancer patients are non-adherent to their medication. Several factors have been linked to non-adherence in cancer patients. In particular, the experience of side-effects, communication style between patients and HCPs5 and beliefs about treatment necessity seem to play an important role in adherence behaviour.(6) Other factors, such as illness severity and patients’ perceptions of their illness, have also been identified as influencing patients’ behaviour when they try to follow their treatment regimes.(2) It is also common that patients simply forget to take their medication.
Side-effects
Patients’ experience of side-effects, such as hot flushes, night sweats,  concentration and memory problems, have been found contribute to non-adherent behaviour in breast cancer patients on maintenance therapy.(6) In addition, low-grade adverse events, including nausea, fatigue and muscle cramps, have been found to predict non-adherence to imatinib in chronic myeloid leukaemia (CML) patients.(7) In this context, it is noteworthy that patients and HCPs seem to have different perceptions of what is important in their treatment regimes.
HCPs seem to focus on the seriousness of adverse events in relation to treatment side-effects, whereas patients tend to look at the consequences on their quality of life.(8) This reflection could explain why some patients do not adhere to their medication regime despite being diagnosed with a life-threatening illness. For example, a side-effect that is minor from a medical point of view but which impacts considerably on the patient’s day-to-day life may be perceived as ‘serious’ from a patient’s point of view. While both patients and HCPs aim to improve patient well-being, they can have different objectives in achieving this which, in turn, can lead to a change in patients’ medication taking behaviour.
 
Lack of communication
This highlights the importance of appropriate communication between HCPs and patients, so that the challenges the patients face in their day-to-day lives can be understood and supported. A recent meta-analysis of 106 cross-sectional studies and 21 interventions reported that patients whose HCP communicated well (for example, offered verbal and non-verbal support and encouragement, allowed open discussion and facilitated patient involvement in decision making) had 19% higher adherence than did those whose HCP did not communicate well.(5)
Perception of illness and treatment
Patients’ perceptions of both their illness and treatment are also likely to have an impact on treatment adherence. Meta-analysis has shown that cognitive representations of the symptoms, proposed timelines, perceived consequences, cause and possibility of controlling an illness have proven useful in explaining illness-related behaviour, such as adherence, in a range of studies across illness groups and settings.(9)
Additionally, thoughts and feelings about the treatment prescribed have been found to predict non-adherence in many illnesses, including cancer.(6) Most research in this area has focused on unhelpful beliefs, such as doubts about personal necessity for treatment, concerns about potential adverse effects and negative beliefs about medicines in general as a class of treatment.(10)
Forgetting doses
Forgetting doses is the main reason for unintentional non-adherence. For example, Atkins and Fallowfield reported that forgetting was the main cause of non-adherence in breast cancer patients where 83% of the total sample of 131 women reported forgetting doses.(11) Forgetting was also the main reason reported for unintentional non-adherence in patients prescribed imatinib for CML.(12) Treatment beliefs may also have an impact on whether the patient will remember to take their medication or not(13) For example, a patient who does not want to take the medication may be more prone to forget.
Depression
Depression has also been shown to impact negatively on adherence in a range of chronic illnesses, including cancer.(14) Considering that the prevalence of depression in cancer patients has been reported to be as high as 45%,(15)  this is clearly another issue that needs to be considered in terms of supporting patients’ adherence to oral cancer treatments.
Improving adherence
Identifying barriers
The first step towards supporting a patient’s treatment adherence is to identify potential barriers. And although research has indicated factors that are associated with non-adherence in different disease populations, each patient is unique, as are the challenges and beliefs that influence medication- taking behaviours in the individual. Consequently, effective communication between HCPs and patients is essential.
Appropriate communication
Indeed, appropriate communication can improve adherence behaviour and encourage patients to follow their treatment recommendations.(5) In particular, HCPs should monitor patients’ adherence and try to identify the potential barriers to adherence in individuals. It is also important to talk more frequently about the importance of taking medication as prescribed when aiming to improve treatment adherence. In addition, the possible negative consequences of non-adherence need to be conveyed to the patient in an easily understood and sensitive manner. It is also important to reinforce effective patient behaviour.(2) In this context, allied healthcare professionals such as nurses, pharmacists and onco-psychologists are indispensable, as patients are often reluctant to disclose non-adherence to their treating physician.
Patient support 
When aiming to increase adherence to oral cancer medicines, it is also crucial that professional patient support include the assessment of patients’ quality of life, in particular in light of patients experiencing side-effects and conversations on how quality of life could be improved. For example, patients could be asked more specifically about their understanding and experience of side effects and encouraged to talk about the struggles they encounter in their day-to-day life, and not only in the presence higher grade adverse events.
Adherence aids
There are a range of technologies and strategies to support patients who forget to take their medication. For example, the patient can use an alarm that reminds him/her to take doses. Another commonly used device is the monitored dosing box, which has small compartments corresponding to different timings of each dose. The dosing box generally does not remind the patient to take doses, but on checking the box patients can at least know if they have forgotten to take a dose. HCPs can also support the patient in developing a routine for taking the tablets. For example, it can be suggested that the patient links taking the medication with another daily routine, such as having dinner, if the particular treatment can be taken with food, or brushing their teeth. The patient may also be advised to put a reminder note somewhere visible, such as on the bathroom mirror or the fridge door.
Addressing depression
Addressing depression in cancer patients is essential to improve quality of life and to support treatment adherence. Obviously, this should be done by HCPs who are qualified to provide such interventions, and this calls for ready access to psychological services for all cancer patients.
Established protocols
Considering how common non-adherence is and the negative consequences of not taking medication as prescribed, hospitals and healthcare trusts should have established protocols for addressing adherence issues. Indeed, a survey conducted in France, Italy and Spain found that hospitals that provided individual counselling on adherence or had established adherence protocols had higher MPRs than hospitals that did not.(16)
Conclusions
Non-adherence among cancer patients is common and this has adverse clinical and economic consequences. Approaches to reduce non-adherence to oral cancer medicines should include ongoing supportive communication between the HCP and the patient, proactive management of low-grade adverse events and provision of adherence aids and strategies for patients who might be prone to forget doses or are otherwise not able to take their medication as prescribed.
Finally, the patient must be allowed to make the decision on whether or not to take a cancer treatment as prescribed. However, we have to ensure that the patient has received the best possible information and support to be able to make that decision and proceed with confidence.
Key points
  • Non-adherence to oral anticancer medicines is common across most cancer types and illness stages.
  • To support adherence, it is essential to address quality of life and to manage medication side effects.
  • Patients should be provided with appropriate information regarding the necessity of treatment and consequences of nonadherence, and given reassurance regarding the likelihood of adverse events.
  • Adherence behaviour should be routinely monitored in clinical practice (see Box 1) and adherent patients should be given ongoing encouragement to maintain the behaviour.
  • Relationships between healthcare professionals and patients based on trust and collaboration are essential when aiming to improve treatment adherence and facilitate effective communication.
References
  1. Dimatteo MR. Variations in patients’ adherence to medical recommendations: a quantitative review of 50 years of research. Medical Care 2004;42(3):200–9.
  2. Ruddy K, Mayer E, Partridge A. Patient adherence and persistence with oral anticancer treatment. CA: Cancer J Clin 2009;59(1):56–66.
  3. Chlebowski RT, Geller ML. Adherence to endocrine therapy for breast cancer. Oncology 2006;71(1–2):1–9.
  4. Darkow T et al. Treatment interruptions and non-adherence with imatinib and associated healthcare costs: A retrospective analysis among managed care patients with chronic myelogenous leukaemia. Pharmacoeconomics 2007;25(6): 481–96.
  5. Haskard Zolnierek KB, DiMatteo MR. Physician communication and patient adherence to treatment: a meta-analysis. Med Care 2009;47(8): 826–34.
  6. Grunfeld EA et al. Adherence beliefs amongst breast cancer patients taking tamoxifen. Patient Educ Couns 2005;59:97–102.
  7. Marin D et al. 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 2010;28(14):2381–9.
  8. Fellowes D. Tolerability of hormone therapies for breast cancer: how informative are documented symptom profiles in medical notes for ‘well-tolerated’ treatments? Breast Canc Res Treat 2001;66(1):73–81.
  9. Hagger MS, Orbell S. A meta-analytic review of the common-sense model of illness. Psychol Health 2003;18(2):141–84.
  10. Horne R, Clatworthy J. Adherence to advice and treatment. In French DN et al (eds), Health Psychology (2nd ed);2010:175–88.
  11. Atkins L, Fallowfield L. Intentional and non-intentional non-adherence to medication amongst breast cancer patients. Eur J Cancer 2006;42(14):2271–6.
  12. Eliasson L et al. Exploring chronic myeloid leukemia patients’ reasons for not adhering to the oral anticancer drug imatinib as prescribed. Leukemia Res 2011;35(5):626–30.
  13. Gadkari AS, McHorney CA. Unintentional non-adherence to chronic prescription medications: How unintentional is it really? BMC Health Serv Res 2012;12:98.
  14. DiMatteo MR, Lepper HS, Croghan TW. Depression is a risk factor for noncompliance with medical treatment: Meta-analysis of the effects of anxiety and depression on patient adherence. Arch Int Med 2004;160(14):2101–7.
  15. Pirl WF. Evidence report on the occurrence, assessment, and treatment of depression in cancer patents. J Natl Cancer Inst Monograph 2004;32:32–9.
  16. Guilhot F et al. A global retrospective and physician based analysis of adherence to tyrosine kinase inhibitor (TKI) therapies for chronic myeloid leukemia (CML). Blood 2010;116(21):644.


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