Barriers and Unmet Educational Needs Regarding Implementation of Medication Adherence Management Across Europe: Insights from COST Action ENABLE.

BACKGROUND: Medication adherence is essential for the achievement of therapeutic goals. Yet, the World Health Organization estimates that 50% of patients are nonadherent to medication and this has been associated with 125 billion euros and 200,000 deaths in Europe annually. OBJECTIVE: This study aimed to unravel barriers and unmet training needs regarding medication adherence management across Europe. DESIGN: A cross-sectional study was conducted through an online survey. The final survey contained 19 close-ended questions. PARTICIPANTS: The survey content was informed by 140 global medication adherence experts from clinical, academic, governmental, and patient associations. The final survey targeted healthcare professionals (HCPs) across 39 European countries. MAIN MEASURES: Our measures were barriers and unmet training needs for the management of medication adherence across Europe. KEY RESULTS: In total, 2875 HCPs (pharmacists, 40%; physicians, 37%; nurses, 17%) from 37 countries participated. The largest barriers to adequate medication adherence management were lack of patient awareness (66%), lack of HCP time (44%), lack of electronic solutions (e.g., access to integrated databases and uniformity of data available) (42%), and lack of collaboration and communication between HCPs (41%). Almost all HCPs pointed out the need for educational training on medication adherence management. CONCLUSIONS: These findings highlight the importance of addressing medication adherence barriers at different levels, from patient awareness to health system technology and to fostering collaboration between HCPs. To optimize patient and economic outcomes from prescribed medication, prerequisites include adequate HCP training as well as further development of digital solutions and shared health data infrastructures across Europe.

Pan-European survey on medication adherence management by healthcare professionals.

AIMS: While medication adherence (MA) is a key prerequisite for achieving optimal clinical and economic outcomes, nonadherence is highly prevalent. Assessing how healthcare professionals (HCPs) in Europe manage MA, focusing on measurement, reporting and interventions, is the subject of this study. METHODS: A cross-sectional study was conducted among 40 European countries and quantitative analysis was conducted via an online survey. The multi-language online survey was created using Webropol 3.0 survey and reporting tool. Descriptive statistics and chi-squared tests were applied. RESULTS: In total, 2875 HCPs (pharmacists: 39.9%; physicians: 36.7%; nurses: 16.4%) from 37 European countries participated. The most used methods for MA assessment were direct communication with patients (86.4%) and referring to personal patient records (56.7%) (P < 0.0001). Physicians (74.9%) and nurses (58.8%) were more aware of problems related to MA in contrast to pharmacists (48.6%) (P < 0.001). Almost all HCPs (92.6%) indicated that MA-enhancing interventions involved mainly direct communication with nonadherent patients (93.3%) and their caregivers (55.7%). Medication review and related optimization of therapy were mainly performed in Western European countries (46.8%). Technological solutions were ranked as one of the less applied approaches (10-15%) (P < 0.001). CONCLUSIONS: HCPs in all European regions recognize MA management as an integral element of overall patient-centred care. More efforts are needed to ensure timely, adequate and relevant MA assessment, reporting and improvement and involvement of all HCPs, especially among pharmacists who were generally less aware of MA issues. Promotion and use of digital technological solutions should be the focus of current and future clinical practice to optimize MA management processes.

Organizational commitment and job satisfaction among nurses in Serbia: a factor analysis.

BACKGROUND: One of the basic prerequisites of efficient organizational management in health institutions is certainly monitoring and measuring satisfaction of employees and their commitment to the health institution in which they work. The aim of this article was to identify and test factors that may have a predictive effect on job satisfaction and organizational commitment. METHODS: We conducted a cross-sectional study that included 1,337 nurses from Serbia. Data were analyzed by using exploratory factor analysis, multivariate regressions, and descriptive statistics. RESULTS: The study identified three major factors of organizational commitment: affective commitment, disloyalty, and continuance commitment. The most important predictors of these factors were positive professional identification, extrinsic job satisfaction, and intrinsic job satisfaction (p < .0001). Predictors significantly affecting both job satisfaction and organizational commitment were identified as well; the most important of which was positive professional identification (p < .0001). CONCLUSIONS: This study identified the main factors affecting job satisfaction and organizational commitment of nurses, which formed a good basis for the creation of organizational management policy and human resource management policy in health institutions in Serbia.

Cancer incidence and mortality in Serbia 1999-2009.

BACKGROUND: Despite the increase in cancer incidence in the last years in Serbia, no nation-wide, population-based cancer epidemiology data have been reported. In this study cancer incidence and mortality rates for Serbia are presented using nation-wide data from two population-based cancer registries. These rates are additionally compared to European and global cancer epidemiology estimates. Finally, predictions on Serbian cancer incidence and mortality rates are provided. METHODS: Cancer incidence and mortality was collected from the cancer registries of Central Serbia and Vojvodina from 1999 to 2009. Using age-specific regression models, we estimated time trends and predictions for cancer incidence and mortality for the following five years (2010-2014). The comparison of Serbian with European and global cancer incidence/mortality rates, adjusted to the world population (ASR-W) was performed using Serbian population-based data and estimates from GLOBOCAN 2008. RESULTS: Increasing trends in both overall cancer incidence and mortality rates were identified for Serbia. In men, lung cancer showed the highest incidence (ASR-W 2009: 70.8/100,000), followed by colorectal (ASR-W 2009: 39.9/100,000), prostate (ASR-W 2009: 29.1/100,000) and bladder cancer (ASR-W 2009: 16.2/100,000). Breast cancer was the most common form of cancer in women (ASR-W 2009: 70.8/100,000) followed by cervical (ASR-W 2009: 25.5/100,000), colorectal (ASR-W 2009: 21.1/100,000) and lung cancer (ASR-W 2009: 19.4/100,000). Prostate and colorectal cancers have been significantly increasing over the last years in men, while this was also observed for breast cancer incidence and lung cancer mortality in women. In 2008 Serbia had the highest mortality rate from breast cancer (ASR-W 2008: 22.7/100,000), among all European countries while incidence and mortality of cervical, lung and colorectal cancer were well above European estimates. CONCLUSION: Cancer incidence and mortality in Serbia has been generally increasing over the past years. For a number of cancer sites, incidence and mortality is alarmingly higher than in the majority of European regions. For this increasing trend to be controlled, the management of risk factors that are present among the Serbian population is necessary. Additionally, prevention and early diagnosis are areas where significant improvements could still be made.

Pharmacoeconomic Analysis of the Different Therapeutic Approaches in Control of Bovine Mastitis: Phytotherapy and Antimicrobial Treatment.

Mastitis in dairy cows is responsible for major economic losses on dairy farms worldwide as the most expensive and prevalent disease in dairy cattle. In spite of the fact that antibiotic therapy still remains the main treatment strategy for bovine mastitis, concerns about the shortcomings of this treatment approach are continuously raised. Hence, research on alternative treatments with increased effectiveness and reduced costs is needed. Therefore, we conducted a pharmacoeconomic analysis of conventional antibiotic vs. a proposed Phyto-Bomat treatment based on essential oils in bovine mastitis therapy. Treatments were compared from the farmer's perspective in the domain of costs (expressed in total, direct and indirect, cost differences) and effectiveness (expressed in daily milk yield differences). Economic calculations were based on data from a dairy farm in Serbia. The average cost of conventional antibiotic treatment was estimated at EUR 80.32 consisting of therapy costs, veterinary services and milk rejection costs at EUR 16.54, EUR 17.68 and EUR 46.10, respectively. The average cost of Phyto-Bomat treatment was estimated at EUR 76.34 with therapy costs of EUR 34.34, veterinary costs of EUR 32.00 and rejection of milk costs of only EUR 10.00. Therefore, Phyto-Bomat results in cost savings approximating EUR 4 per each mastitis episode with the highest cost reductions obtained in milk rejection costs. This estimation of Phyto-Bomat's economic benefits could be used as a starting point for the inclusion of this formulation as an alternative treatment approach with a focus on subclinical mastitis since it contributes to most of the financial losses.

Informing decision makers seeking to improve vaccination programs: case-study Serbia.

Background:The optimisation of vaccine policies before their implementation is beholden upon public health decision makers, seeking to maximise population health. In this case study in Serbia, the childhood vaccines under consideration included pneumococcal conjugate vaccination (PCV), rotavirus (RV) vaccination and varicella zoster virus (VZV) vaccination. Objective: The objective of this study is to define the optimal order of introduction of vaccines to minimise deaths, quality adjusted life years (QALYs) lost, or hospitalisation days, under budget and vaccine coverage constraints. Methods: A constrained optimisation model was developed including a static multi-cohort decision-tree model for the three infectious diseases. Budget and vaccine coverage were constrained, and to rank the vaccines, the optimal solution to the linear programming problem was based upon the ratio of the outcome (deaths, QALYs or hospitalisation days) per unit of budget. A probabilistic decision analysis Monte Carlo simulation technique was used to test the robustness of the rankings. Results: PCV was the vaccine ranked first to minimise deaths, VZV vaccination for QALY loss minimisation and RV vaccination for hospitalisation day reduction. Sensitivity analysis demonstrated the most robust ranking was that for PCV minimizing deaths. Conclusion: Constrained optimisation modelling, whilst considering all potential interventions currently, provided a comprehensive and rational approach to decision making.

European Network to Advance Best Practices and Technology on Medication Adherence: Mission Statement.

Medication non-adherence is associated with almost 200,000 deaths annually and €80-125 billion in the European Union. Novel technological advances (smart pill bottles, digital inhalers and spacers, electronic pill blisters, e-injection pens, e-Health applications, big data) could help managing non-adherence. Healthcare professionals seem however inadequately informed about non-adherence, availability of technological solutions in daily practice is limited, and collaborative efforts to push forward their implementation are scarce. The European Network to Advance Best practices and technoLogy on medication adherencE (ENABLE, COST Action 19132) aims to 1) raise awareness of adherence enhancing solutions, 2) foster knowledge on medication adherence, 3) accelerate clinical application of novel technologies and 4) work collaboratively towards economically viable policy, and implementation of adherence enhancing technology across healthcare systems.

Microcosting Study of Rituximab Subcutaneous Injection Versus Intravenous Infusion.

PURPOSE: The goal of this study is to identify and compare all direct costs of intravenous and subcutaneous rituximab given to patients with diffuse large B-cell lymphoma in the Netherlands. METHODS: Using a prospective, observational, bottom-up microcosting study, we collected primary data on the direct medical costs of the preparation, administration, and acquisition of rituximab. Drug costs and costs of drug wastage, labor costs, material costs, and outpatient costs were identified using standardized forms, structured using prices from official pricelists, and compared for the intravenous and subcutaneous forms of rituximab. FINDINGS: Measurements were taken on 53 rituximab administrations (33 intravenous and 20 subcutaneous) and on 13 rituximab preparation (7 intravenous and 6 subcutaneous). The mean total costs were €2176.77 for the intravenous infusion and €1911.09 for the subcutaneous injection. The estimated difference of €265.17 (95% CI, €231.99-`€298.35) per administration was mainly attributable to differences in time spent in the chemotherapy unit, related outpatient costs, drug wastage, and drug costs. IMPLICATIONS: Rituximab administered in the form of subcutaneous injection is less costly than its intravenous form. With their equal effectiveness taken into account, subcutaneous rituximab administration can result in significant savings when transferred to the total diffuse large B-cell lymphoma population in the Netherlands.

Reimbursement of targeted cancer therapies within 3 different European health care systems.

PURPOSE: Targeted cancer therapies (TCTs) are drugs that specifically act on molecular targets within the cancer cell, causing its regression and/or destruction. Although TCTs offer clinically important gains in survival in one of the most challenging therapeutic areas, these gains are followed by considerable increases in health care expenditures. The aim of this study was to identify differences in the recommendations for TCTs in 3 European health care systems (Serbian, Scottish, and Dutch) and to examine the role of pharmacoeconomic (PE) assessments in such recommendations. METHODS: A list of currently approved TCTs cited from the European Medicines Agency was cross-referenced with drug reimbursement reports issued by the National Health Insurance Fund for Serbia, the Scottish Medicines Consortium for Scotland, and the National Health Institute for the Netherlands. The following key variables were gathered from the reports: drug indication, registration status, reimbursement status, and outcome of the PE evaluation. FINDINGS: There were 41 TCTs approved by the European Medicines Agency for 70 cancer indications. Of the total number of TCT indications, 20 were reimbursed in Serbia, and 25 are still without a decision from the national agency. The remaining TCT indications (n = 25) are not registered in Serbia. None of the submissions or the PE analyses were publicly available. The Scottish Medicines Consortium positively assessed 26 TCT indications and rejected 30. All appraisals were published, and the majority contained full PE assessments. Finally, the Dutch agency accepted 60 TCT indications and disapproved the use of 1. The majority of reimbursed drugs were exempted from PE evaluation in accordance with 2 recent policies regarding expensive hospital drugs. IMPLICATIONS: In the 3 examined health care systems, the reimbursement status of the TCTs differed significantly. Level of PE application within the TCT evaluation procedures seemed to largely affect the final reimbursement decisions. Although, there are special policies in the Netherlands that enabled fast access for 98% of the TCTs that applied for reimbursement, a clear definition of cost-effectiveness threshold and strict requirements for full cost utility assessments in Scotland led to acceptance of only 46% of the TCT submissions. More precise PE guidelines must still be designed for TCT reimbursement in Serbia. Guidelines must account for specific epidemic and economic conditions of the country and could build on the experiences of Scotland and the Netherlands.

Cost-effectiveness of everolimus for second-line treatment of metastatic renal cell carcinoma in Serbia.

BACKGROUND: New targeted therapeutics for metastatic renal cell carcinoma (mRCC) enable an increment in progression-free survival (PFS) ranging from 2 to 6 months. Compared with best supportive care, everolimus demonstrated an additional PFS of 3 months in patients with mRCC whose disease had progressed on sunitinib and/or sorafenib. The only targeted therapy for mRCC currently reimbursed in Serbia is sunitinib. OBJECTIVE: The aim of this study was to estimate the cost-effectiveness and the budget impact of the introduction of everolimus in Serbia in comparison to best supportive care, for mRCC patients refractory to sunitinib. METHODS: A Markov model was designed corresponding with Serbian treatment protocols. A health care payer perspective was taken, including direct costs only. Treated and untreated cohorts were followed up over 18 cycles, each cycle lasting 8 weeks, which covered the lifetime horizon of mRCC patients refractory to the first-line treatment. Annual discounted rates of 1.5% for effectiveness and 3% for costs were applied. Transitions between health states were modeled by time-dependent probabilities extracted from published Kaplan-Meier curves of PFS and overall survival (OS). Utility values were obtained from the appraisals of other mRCC treatments. One-way and probabilistic sensitivity analyses were done to test the robustness and uncertainty of the base-case estimate. Lastly, the potential impacts of everolimus on the overall health care expenditures on annual and 4-year bases were estimated in the budget-impact analysis. RESULTS: The incremental cost-effectiveness ratio for everolimus was estimated at €86,978 per quality-adjusted life-year. Sensitivity analysis identified the hazard multiplier, a statistical approximator of OS gain, as the main driver of everolimus cost-effectiveness. Furthermore, probabilistic sensitivity analyses revealed a wide 95% CI around the base-case incremental cost-effectiveness ratio estimate (€32,594-€425,258 per quality-adjusted life-year). Finally, an average annual budgetary impact of everolimus in first 4 years after its potential reimbursement would be around €270,000, contributing to <1% of the total budget in Serbian oncology. CONCLUSIONS: Everolimus as a second-line treatment of mRCC is not likely to be a cost-effective option under the present conditions in Serbia, with a relatively limited impact on its budget in oncology. A major constraint on the estimation of the cost-effectiveness of everolimus relates to the uncertainty around the everolimus effect on extending OS. However, prior to a final decision on the acceptance/rejection of everolimus, reassessment of the whole therapeutic group might be needed to construct an economically rational treatment strategy within the mRCC field.