Lina Eliasson

Adherence Is the Critical Factor for Achieving Molecular Responses in Patients With Chronic Myeloid Leukemia Who Achieve Complete Cytogenetic Responses on Imatinib

PURPOSE There is a considerable variability in the level of molecular responses achieved with imatinib therapy in patients with chronic myeloid leukemia (CML). These differences could result from variable therapy adherence. METHODS Eighty-seven patients with chronic-phase CML treated with imatinib 400 mg/d for a median of 59.7 months (range, 25 to 104 months) who had achieved complete cytogenetic response had adherence monitored during a 3-month period by using a microelectronic monitoring device. Adherence was correlated with levels of molecular response. Other factors that could influence outcome were also analyzed. RESULTS Median adherence rate was 98% (range, 24% to 104%). Twenty-three patients (26.4%) had adherence <or= 90%; in 12 of these patients (14%), adherence was <or= 80%. There was a strong correlation between adherence rate (<or= 90% or > 90%) and the 6-year probability of a 3-log reduction (also known as major molecular response [MMR]) in BCR-ABL1 transcripts (28.4% v 94.5%; P < .001) and also complete molecular response (CMR; 0% v 43.8%; P = .002). Multivariate analysis identified adherence (relative risk [RR], 11.7; P = .001) and expression of the molecular human organic cation transporter-1 (RR, 1.79; P = .038) as the only independent predictors for MMR. Adherence was the only independent predictor for CMR. No molecular responses were observed when adherence was <or= 80% (P < .001). Patients whose imatinib doses were increased had poor adherence (86.4%). In this latter population, adherence was the only independent predictor for inability to achieve an MMR (RR, 17.66; P = .006). CONCLUSION In patients with CML treated with imatinib for some years, poor adherence may be the predominant reason for inability to obtain adequate molecular responses.

Poor adherence is the main reason for loss of CCyR and imatinib failure for chronic myeloid leukemia patients on long-term therapy.

We studied the relation between adherence to imatinib measured with microelectronic monitoring systems and the probabilities of losing a complete cytogenetic response (CCyR) and of imatinib failure in 87 CCyR chronic myeloid leukemia patients receiving long-term therapy. We included in our analysis the most relevant prognostic factors described to date. On multivariate analysis, the adherence rate and having failed to achieve a major molecular response were the only independent predictors for loss of CCyR and discontinuation of imatinib therapy. The 23 patients with an adherence rate less than or equal to 85% had a higher probability of losing their CCyR at 2 years (26.8% vs 1.5%, P = .0002) and a lower probability of remaining on imatinib (64.5% vs 90.6%, P = .006) than the 64 patients with an adherence rate more than 85%. In summary, we have shown that poor adherence is the principal factor contributing to the loss of cytogenetic responses and treatment failure in patients on long-term therapy.

Quality of medication use in primary care - mapping the problem, working to a solution: a systematic review of the literature

BackgroundThe UK, USA and the World Health Organization have identified improved patient safety in healthcare as a priority. Medication error has been identified as one of the most frequent forms of medical error and is associated with significant medical harm. Errors are the result of the systems that produce them. In industrial settings, a range of systematic techniques have been designed to reduce error and waste. The first stage of these processes is to map out the whole system and its reliability at each stage. However, to date, studies of medication error and solutions have concentrated on individual parts of the whole system. In this paper we wished to conduct a systematic review of the literature, in order to map out the medication system with its associated errors and failures in quality, to assess the strength of the evidence and to use approaches from quality management to identify ways in which the system could be made safer.MethodsWe mapped out the medicines management system in primary care in the UK. We conducted a systematic literature review in order to refine our map of the system and to establish the quality of the research and reliability of the system.ResultsThe map demonstrated that the proportion of errors in the management system for medicines in primary care is very high. Several stages of the process had error rates of 50% or more: repeat prescribing reviews, interface prescribing and communication and patient adherence. When including the efficacy of the medicine in the system, the available evidence suggested that only between 4% and 21% of patients achieved the optimum benefit from their medication. Whilst there were some limitations in the evidence base, including the error rate measurement and the sampling strategies employed, there was sufficient information to indicate the ways in which the system could be improved, using management approaches. The first step to improving the overall quality would be routine monitoring of adherence, clinical effectiveness and hospital admissions.ConclusionBy adopting the whole system approach from a management perspective we have found where failures in quality occur in medication use in primary care in the UK, and where weaknesses occur in the associated evidence base. Quality management approaches have allowed us to develop a coherent change and research agenda in order to tackle these, so far, fairly intractable problems.

Patient adherence to tyrosine kinase inhibitor therapy in chronic myeloid leukemia

Dramatically improved survival associated with tyrosine kinase inhibitor (TKI) therapy has transformed the disease model for chronic myeloid leukemia (CML) to one of long‐term management, but treatment success is challenged with poor medication adherence. Many risk factors associated with poor adherence can be ameliorated by close monitoring, dose modification, and supportive care. Controlling risk factors for poor adherence in combination with patient education that includes direct communication between the health care team and the patient are essential components for maximizing the benefits of TKI therapy. Am. J. Hematol. 87:687–691, 2012.

Unintentional non-adherence: can a spoon full of resilience help the medicine go down?

Non-adherence to medication is a ‘worldwide problem of striking magnitude’.1 It has consequences for the health of patients and is a great concern for healthcare providers in terms of patient outcomes and healthcare costs. Theoretical research has mainly focused on intentional non-adherence: for example, when people choose not to take their medication. However, unintentional non-adherence also accounts for a significant proportion of the problem: when people mean to take their medication in the right way but do not. This area is under-researched. In this paper, we bring a new perspective to this problem by exploring what contribution ‘resilience’ could make to it. Resilience engineering focuses on a systems ability to maintain performance, avoid error, compensate for poor circumstances and cope with disturbances. So, rather than focus on how things go wrong, we propose to exploit and enhance how things go right. The National Health Service in England processed 962 million prescriptions in 2011, which had an ingredient cost of £8.8 billion,2 and it is estimated that 30%–50% of prescribed medication are not taken correctly.3 A report prepared for a summit of European health ministers in 2012 estimated that non-adherence contributes approximately 57% of

Developing the Diagnostic Adherence to Medication Scale (the DAMS) for use in clinical practice.

500 billion total avoidable costs attributed to suboptimal medicine use globally each year.4 Horne et al 3 provide a broad and comprehensive review of the research in this area. Their report shows that the problem is complex and multifaceted, and they call for more research to tackle this important issue. They argue that improving the effectiveness of adherence interventions could have a greater impact on public health than improvements in specific medical treatments.3 Haynes et al 5 note that current successful interventions for non-adherence are multifaceted, complex, labour intensive and at best have modest effects; they call for innovative approaches to assist …

Treatment Adherence in Type 1 Hereditary Tyrosinaemia (HT1): A Mixed-Method Investigation into the Beliefs, Attitudes and Behaviour of Adolescent Patients, Their Families and Their Health-Care Team

BackgroundThere is a need for an adherence measure, to monitor adherence services in clinical practice, which can distinguish between different types of non-adherence and measure changes over time. In order to be inclusive of all patients it needs to be able to be administered to both patients and carers and to be suitable for patients taking multiple medications for a range of clinical conditions. A systematic review found that no adherence measure met all these criteria. We therefore wished to develop a theory based adherence scale (the DAMS) and establish its content, face and preliminary construct validity in a primary care population.MethodsThe DAMS (consisting of 6 questions) was developed from theory by a multidisciplinary team and the questions were initially tested in small patient populations. Further to this, patients were recruited when attending a General Practice and interviewed using the DAMS and two other validated self-reported adherence measures, theMorisky-8 and Lu questionnaires. A semi-structured interview was used to explore acceptability and reasons for differences in responses between the DAMS and the other measures. Descriptive data were generated and Spearman rank correlation tests were used to identify associations between the DAMS and the other adherence measures.ResultsOne hundred patients completed the DAMS in an average of 1 minute 28 seconds and reported finding it straightforward to complete. An adherence score could not be calculated for the 4(4%) patients only taking ‘when required’ medication. Thirty six(37.5%) of the remaining patients reported some non-adherence. Adherence ratings of the DAMS were significantly associated with levels of self reported adherence on all other measures Spearman Rho 0.348-0.719, (p < 0.01). Differences in trends could generally be explained by qualitative data.ConclusionThe DAMS has been developed for routine monitoring of adherence in clinical practice. It was acceptable to patients taking single or multiple medication and valid when tested against other adherence measures. However, ‘when required’ medication needs to be excluded. Further tests of the DAMS against objective measures such as MEMS are in progress and reliability needs to be established. Further investigation of the carers’ version of the DAMS is required.

Suitability of measures of self-reported medication adherence for routine clinical use: a systematic review.

BACKGROUND Type 1 hereditary tyrosinaemia (HT1) is a rare metabolic disorder caused by an enzymatic defect in the metabolism of the amino acid tyrosine. Primary treatment for HT1 is nitisinone (Orfadin) in conjunction with a low-tyrosine/phenylalanine diet. The appropriate use of nitisinone medication and adhering to specialist diet is thus central to the successful management of HT1. OBJECTIVE To date, no published research has examined adherence (to medication and diet) and factors that influence it in the context of HT1. This study aimed to ascertain the extent to which non-adherence is a problem in this patient population, identify perceived barriers and facilitators to treatment adherence and explore the role of illness beliefs and treatment perceptions in treatment management. METHODS The present study used a combination of qualitative interviews and quantitative survey methods with patients, carers and health-care professionals (HCPs). RESULTS This study found adherence to medication to be high amongst patients with HT1 and their carers who administer it. However, adherence to diet was reported to be much lower. A key factor influencing adherence to diet was age, with adolescents reported to have most difficulty adhering. CONCLUSIONS The results indicate that adherence to dietary instructions becomes more problematic as children with HT1 grow older. Greater involvement in managing their condition and in their consultation at an early stage may have a positive impact on future adherence by increasing their investment and understanding of the treatment regime, potentially making adherence rates more stable and less influenced by moving through different life stages.