Economic evaluation of pharmacogenomic-guided antiplatelet treatment in Spanish patients suffering from acute coronary syndrome participating in the U-PGx PREPARE study.

BACKGROUND: Cardiovascular diseases and especially Acute Coronary Syndrome (ACS) constitute a major health issue impacting millions of patients worldwide. Being a leading cause of death and hospital admissions in many European countries including Spain, it accounts for enormous amounts of healthcare expenditures for its management. Clopidogrel is one of the oldest antiplatelet medications used as standard of care in ACS. METHODS: In this study, we performed an economic evaluation study to estimate whether a genome-guided clopidogrel treatment is cost-effective compared to conventional one in a large cohort of 243 individuals of Spanish origin suffering from ACS and treated with clopidogrel. Data were derived from the U-PGx PREPARE clinical trial. Effectiveness was measured as survival of individuals while study data on safety and efficacy, as well as on resource utilization associated with each adverse drug reaction were used to measure costs to treat these adverse drug reactions. A generalized linear regression model was used to estimate cost differences for both study groups. RESULTS: Based on our findings, PGx-guided treatment group is cost-effective. PGx-guided treatment demonstrated to have 50% less hospital admissions, reduced emergency visits and almost 13% less ADRs compared to the non-PGx approach with mean QALY 1.07 (95% CI, 1.04-1.10) versus 1.06 (95% CI, 1.03-1.09) for the control group, while life years for both groups were 1.24 (95% CI, 1.20-1.26) and 1.23 (95% CI, 1.19-1.26), respectively. The mean total cost of PGx-guided treatment was 50% less expensive than conventional therapy with clopidogrel [€883 (95% UI, €316-€1582), compared to €1,755 (95% UI, €765-€2949)]. CONCLUSION: These findings suggest that PGx-guided clopidogrel treatment represents a cost-effective option for patients suffering from ACS in the Spanish healthcare setting.

Economic evaluation in psychiatric pharmacogenomics: a systematic review.

Nowadays, many relevant drug-gene associations have been discovered, but pharmacogenomics (PGx)-guided treatment needs to be cost-effective as well as clinically beneficial to be incorporated into standard health care. To address current challenges, this systematic review provides an update regarding previously published studies, which assessed the cost-effectiveness of PGx testing for the prescription of antidepressants and antipsychotics. From a total of 1159 studies initially identified by literature database querying, and after manual assessment and curation of all of them, a mere 18 studies met our inclusion criteria. Of the 18 studies evaluations, 16 studies (88.89%) drew conclusions in favor of PGx testing, of which 9 (50%) genome-guided interventions were cost-effective and 7 (38.9%) were less costly compared to standard treatment based on cost analysis. More precisely, supportive evidence exists for CYP2D6 and CYP2C19 drug-gene associations and for combinatorial PGx panels, but evidence is limited for many other drug-gene combinations. Amongst the limitations of the field are the unclear explanation of perspective and cost inputs, as well as the underreporting of study design elements, which can influence though the economic evaluation. Overall, the findings of this article demonstrate that although there is growing evidence on the cost-effectiveness of genome-guided interventions in psychiatric diseases, there is still a need for performing additional research on economic evaluations of PGx implementation with an emphasis on psychiatric disorders.

Cost-effectiveness analysis of pharmacogenomics-guided clopidogrel treatment in Spanish patients undergoing percutaneous coronary intervention.

Clopidogrel is an antiplatelet drug given to patients before and after having a percutaneous coronary intervention (PCI). Genomic variants in the CYP2C19 gene are associated with variable enzyme activities affecting drug metabolism and hence, patients with reduced or increased enzymatic function have increased risk of bleeding. We conducted a cost-effectiveness analysis to compare a pharmacogenomics versus a non-pharmacogenomics-guided clopidogrel treatment for coronary artery syndrome patients undergoing PCI in the Spanish healthcare setting. A total of 549 patients diagnosed with coronary artery disease followed by PCI were recruited. Dual antiplatelet therapy was administrated to all patients from 1 to 12 months after PCI. Patients were classified into two groups: the Retrospective group was treated with clopidogrel based on the clinical routine practice and the Prospective group were initially genotyped for the presence of CYP2C19 variant alleles before treatment with those carrying more than one CYP2C19 variant alleles given prasugrel treatment. We collected data on established clinical and health outcome measures, including, per treatment arm: the percentage of patients that suffered from (a) myocardial infraction, (b) major bleeding and minor bleeding, (c) stroke, (d) the number of hospitalization days, and (e) the number of days patients spent in Intensive Care Unit. Our primary outcome measure for the cost-effectiveness analysis was Quality Adjusted Life Years (QALYs). To estimate the treatment cost for each patient, individual data on its resource used were combined with unit price data, obtained from Spanish national sources. The analysis predicts a survival of 0.9446 QALYs in the pharmacogenomics arm and 0.9379 QALYs in the non-pharmacogenomics arm within a 1-year horizon. The cumulative costs per patient were €2971 and €3205 for the Prospective and Retrospective groups, respectively. The main cost driver of total cost in both arms was hospitalization costs. The incremental cost-effectiveness ratio (ICER) was negative indicating that the PGx was a dominant option. Our data show that pharmacogenomics-guided clopidogrel treatment strategy may represent a cost-effective choice compared with non-pharmacogenomics-guided strategy for patients undergoing PCI.

Impact of cigarette price differences across the entire European Union on cross-border purchase of tobacco products among adult cigarette smokers.

BACKGROUND: We investigated the impact of cigarette price differences across the European Union (EU) on cross-border tobacco purchasing because of cheaper price among current cigarette smokers. METHODS: Individual-level tobacco-related data (including cross-border tobacco purchasing behavior) were from the Special Eurobarometer 385 (V.77.1), a cross-sectional survey of persons aged ≥15 years from 27 EU Member States during 2012. Country-specific weighted average prices (WAP) per 1000 cigarettes (as of 1 July 2012) were obtained from the European Commission, and divided by 50 to yield WAP per cigarette pack. The dispersion in EU cigarette prices was measured with the coefficient of variation. Multivariate logistic regression was applied to measure the relationship between EU-wide cigarette price differential and cross-border tobacco purchasing because of cheaper price among current cigarette smokers (n=6896). RESULTS: The coefficient of variation for cigarette WAP within the EU was 0.39 (mean price=€3.99/pack). Of all current cigarette smokers in the EU, 26.2% (27.5 million persons) engaged in a cross-border tobacco purchase within the past 12 months, of which 56.3% did so because of cheaper price in another country. EU-wide cigarette price differential was significantly associated with making a cross-border tobacco purchase because of cheaper price (adjusted OR=1.34; 95% CI 1.22 to 1.47). CONCLUSIONS: Reducing differences in cigarette tax and price within the EU, coupled with a stricter limitation on the quantity of cigarettes that it is possible to carry from one Member State to another, may help reduce cross-border tax avoidance strategies.

Citizens' preferences on healthcare expenditure allocation: evidence from Greece.

BACKGROUND OF CONTEXT: Priority setting and resource allocation across various healthcare functions are critical issues in health policy and strategic decision making. As health resources are limited while there are so many health challenges to resolve, consumers and payers have to make difficult decisions about expenditure allocation. OBJECTIVE: Our research focus on the (dis)agreement between citizens' preferences and actual public health expenditure across broad healthcare functions, on whether this (dis)agreement is persistent, on whether various demographic factors amplify this (dis)agreement and to derive useful implications for public health policies. SETTING AND PARTICIPANTS: Using survey data of 3029 citizens in Greece for the year 2012 and employing logit estimation techniques, we analysed the effect of demographic and other factors in shaping citizens' (dis)agreement with public health expenditure allocation. RESULTS: Our results demonstrate the important role of income, family members and residence in shaping citizens' preferences regarding health expenditure priorities in almost all healthcare functions, while other demographic factors such as job, age, gender and marital status do partly associate and play a significant role. CONCLUSIONS: Government should encourage the citizens' participation in the decision-making process in order to eliminate the unveiled and significant disagreement between citizens' preferences and actual public health expenditure across all healthcare functions.

Patient satisfaction with the healthcare system: Assessing the impact of socio-economic and healthcare provision factors.

BACKGROUND: Patient satisfaction is an important measure of healthcare quality as it offers information on the provider's success at meeting clients' expectations and is a key determinant of patients' perspective behavioral intention. The aim of this paper is first to assess the degree of patient satisfaction, and second, to study the relationship between patient satisfaction of healthcare system and a set of socio-economic and healthcare provision indicators. METHODS: This empirical analysis covers 31 countries for the years 2007, 2008, 2009 and 2012. The dependent variable, the satisfaction index, is defined as the patient satisfaction of their country's health system. We first construct an index of patient satisfaction and then, at a second stage, this index is related to socio-economic and healthcare provision variables. RESULTS: Our findings support that there is a strong positive association between patient satisfaction level and healthcare provision indicators, such as nurses and physicians per 100,000 habitants, with the latter being the most important contributor, and a negative association between patient satisfaction level and number of hospital beds. Among the socio-economic variables, public health expenditures greatly shape and positive relate to patient satisfaction, while private spending on health relates negatively. Finally, the elder a patient is, the more satisfied with a country's healthcare system appears to be. CONCLUSIONS: We conclude that there is a strong positive association between patient satisfaction and public health expenditures, number of physicians and nurses, and the age of the patient, while there is a negative evidence for private health spending and number of hospital beds.

The recent and projected public health and economic benefits of cigarette taxation in Greece.

OBJECTIVES: Greece is in an economic crisis compounded by the costs caused by smoking. The present investigation estimates the economic and public health benefits ensuing from the recent cigarette excise tax increase in 2011 and projects the potential benefits from an additional €2.00 per pack cigarette tax increase. METHODS: The effects of the recent cigarette excise tax increase were calculated on outcome measures: total price per pack, including specific excise, ad valorem tax, and value-added tax consumption; tax revenue; and per capita consumption of cigarettes. Additionally, smoking-attributable mortality, years of potential life lost, and productivity losses were estimated. Projected effects of an additional €2.00 per pack tax increase on consumption and tax revenue were also assessed. RESULTS: The cigarette excise tax increase in 2011 created €558 million in new tax revenue. Cigarette consumption reached a recent low of 24.9 billion sticks sold or 2197 sticks per person in 2011, indicating a 16% decrease in per capita cigarette consumption from the previous year. An additional €2.00 per pack increase in Greek cigarette taxes is projected to result in reduced cigarette sales by an additional 20% and lead to an increase in total cigarette tax revenues by nearly €1.2 billion and the prevention of 192,000 premature deaths. CONCLUSIONS: Nations such as Greece, should employ taxation as a crucial measure to promote public health and economic development in such dire times. International economic organisations should aggressively pursue programmes and policies that champion the economic benefits of tobacco taxation.

Going up in ashes? Smoking-attributable morbidity, hospital admissions and expenditure in Greece.

Our aim was to calculate the morbidity, hospitalizations and subsequent hospital costs for the treatment of the smoking-attributable fraction of diseases in Greece using a prevalence-based annual cost approach. In 2011, smoking accounted for 199,028 hospital admissions (8.9% of the national total), with attributable hospital treatment costs calculated at more than €554 million, which represents 10.7% of the national hospital budget. These results pose a compelling reason for the European Union to champion tobacco control as a means of reducing the financial and social burden of disease in Greece and other countries currently facing a financial maelstrom.

Real-world Data and Economic Evaluation of Nivolumab in Previously Treated Non-small Cell Lung Cancer Greek Patients.

BACKGROUND/AIM: Nivolumab is an FDA-approved immune checkpoint inhibitor (ICI) for patients with advanced, pre-treated non-small cell lung cancer (NSCLC). However, treatment profiles and patient outcomes often differ in routine clinical practice while the financial impact of approved therapies is largely unknown. In this study, we investigated the efficacy, tolerability, and economic impact of nivolumab in real-world settings (RWS) in Greece. PATIENTS AND METHODS: Patients diagnosed with advanced pre-treated NSCLC, receiving nivolumab were recruited from October 2015 until November 2019 across 18 different clinical centers in Greece. Endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety. Cost analysis was conducted using a third-party public-payer perspective (National Organization for Healthcare Services Provision; EOPYY). RESULTS: A total of 346 patients, median age 66.5 years, were included. With 43.4 months median follow-up, median PFS was 7.8 months and median OS 15.8 months. The 1-year OS rate was 56.5%, 2-year OS 38.8%, and 3-year OS 27.3%. The ORR was 29.5% and DCR 58.7%, with a median response duration of 26.8 months. Patients with objective response were more likely to experience long-term survival (HR=0.14, p<0.001). Only 8.4% of patients experienced grade 3-4 adverse events. The presence of immune-related adverse events was associated with improved OS (HR=0.77, p=0.043). Nivolumab-associated economic burden accounted for €2,214.10 per cycle for each patient, mainly attributed to drug-acquisition costs. CONCLUSION: This is the first report of real-world efficacy, safety, and economic burden of nivolumab in pre-treated patients with NSCLC in Greece. Indirectly compared to clinical trials, nivolumab was associated with improved efficacy in RWS, further supporting its use in clinical practice and providing insights on clinical prognosticators. The main cost component affecting the nivolumab economic burden was drug-acquisition costs, while toxicity-associated cost was negligible.

Relevance of pharmacogenomics for developing countries in Europe.

Pharmacogenomics holds promise of personalized treatment for patients suffering from many common diseases, particularly those with multiple treatment modalities. Owing to recent advances in the deciphering of the human genome sequence, high throughput genotyping technology has led to the reduction of the overall costs of genetic testing and allowed the inclusion of genotype-related dosing recommendations into drug package inserts, hence enabling the integration of pharmacogenomics into clinical practice. Although pharmacogenomics gradually assumes an important part in routine clinical practice in developed countries, many countries, particularly from the developing world, still do not have access either to the knowledge or the resources to individualize drug therapy. The PharmacoGenetics for Every Nation Initiative (PGENI) aims to fill this gap, by making pharmacogenomics globally applicable, not only by defining population-specific pharmacogenomic marker frequency profiles but also by formulating country-specific recommendations for drug efficacy and safety. This article aims to highlight the PGENI activities in Europe in an effort to make pharmacogenomics readily applicable in the European healthcare systems, particularly those in developing countries.

Informal out-of-pocket payments experience and individuals' willingness-to-pay for healthcare services in Greece.

BACKGROUND: Informal out-of-pocket payments to healthcare providers are not uncommon in the Greek health system. We explore individuals' willingness-to-pay (WTP) to secure zero out-of-pocket full coverage for healthcare services and medications and we estimate the impact of past informal payments and individuals' opinion about the legalization of informal payments on WTP. METHODS: We conducted a survey of 2841 participants from November 2016 to February 2017. We obtained information on WTP using the contingent valuation method. A two-part regression model was used to estimate the association between WTP, informal payments, and respondents' opinion about legalizing such payments. RESULTS: About 80% of the respondents were willing to pay an average of €95 per month to obtain free access to full healthcare coverage and medications. About 65% of the respondents were involved in an informal payment at least once during the past four months with an average payment of €247. Higher informal payments and supportive opinions towards the legalization of informal payments increased the likelihood of WTP and were also positively associated with increased WTP amounts overall (p < 0.001). CONCLUSIONS: This survey reveals that individuals' WTP is critically affected by previous experiences and attitudes towards informal payments. Our results imply that the potential introduction of official fees might not suffice to limit informal payments and suggest the need for stricter regulatory policies.

Management of superficial and deep surgical site infection: an international multidisciplinary consensus.

Surgical site infections represent a considerable burden for healthcare systems. To obtain a consensus on the impact and future clinical and economic needs regarding SSI management in an era of multidrug resistance. A modified Delphi method was used to obtain consensus among experts from five European countries. The Delphi questionnaire was assembled by a steering committee, verified by a panel of experts and administered to 90 experts in 8 different surgical specialities (Abdominal, Cancer, Cardiac, General surgery, Orthopaedic, Thoracic, Transplant and Vascular and three other specialities (infectious disease, internal medicine microbiology). Respondents (n = 52) reached consensus on 62/73 items including that resistant pathogens are an increasing matter of concern and increase both treatment complexity and the length of hospital stay. There was strong positive consensus on the cost-effectiveness of early discharge (ED) programs, improvement of quality of life with ED and association between increased length of stay and economic burden to the hospital. However, established ED protocols were not widely available in their hospitals. Respondents expressed a positive consensus on the usefulness of antibiotics that allow ED. Surgeons are aware of their responsibility in an interdisciplinary team for the treatment of SSI, and of the impact of multidrug-resistant bacteria in the context of SSI. Reducing the length of hospital stays by applying ED protocols and implementing new treatment alternatives is crucial to reduce harm to patients and costs for the hospital.

An Observational Study to Assess the Molecular Epidemiology and Direct Medical Costs of Epidermal Growth Factor Receptor (EGFR) Mutations in Patients with Advanced EGFR Mutation-Positive Non-Small Cell Lung Cancer Treated with Afatinib in Real-World Clinical Settings in Greece.

PURPOSE: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the preferred first-line option for patients with advanced, EGFR-mutant non-small cell lung cancer (NSCLC). Afatinib, a second-generation irreversible EGFR-TKI, has been extensively used in Greece in this setting; however, real-world data regarding molecular epidemiology and financial implications of afatinib use are lacking. MATERIALS AND METHODS: This was an observational, non-interventional, multicenter, retrospective cohort study, based on real-world data collected from the medical charts/records of patients treated with afatinib between 15/03/2015 and 25/06/2020 and were recorded on a web-based data capture system. Cox models were used to assess the prognostic significance of clinicopathological parameters with respect to clinical outcomes of interest. Cost analysis was conducted from a public third-payer perspective, and only direct medical costs reimbursed by the payer were considered. RESULTS: A total of 59 patients were treated with afatinib for their EGFR mutation-positive advanced NSCLC; the median age was 61 years (range: 37-91). Performance status was zero in 61%, and brain metastases were present in 13.6%. Forty-four patients (74.6%) had a deletion in exon 19 only, while nine (15.3%) had a mutation in exon 21, 8 of them in L858R and one in L861Q. At a median follow-up of 41.8 months (95% CI 35.9-51.4), the median PFS was 14.3 months (95% CI 12.2-16.4), and the median OS was 29 months (95% CI 25.6-33.4). Corresponding values for patients with deletion 19 only were 14.3 months (95% CI 11.5-18.5) and 28.1 months (95% CI 21.1-32.6), respectively. The mean expenditure for the treatment of each patient equals €25,333.68; with €21,865.06 being attributed to drug acquisition costs, €3325.35 to monitoring costs and €143.27 to adverse event treatment-related costs. CONCLUSION: Long-term data in the real-world setting in Greece confirm activity, tolerability and cost-effectiveness of afatinib as first-line treatment of patients with advanced EGFR-mutant NSCLC. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov NCT04640870.

Informal out-of-pocket payments for healthcare services in Greece.

BACKGROUND: Informal out-of-pocket (OOP) payments for healthcare services are not unusual in Greece. AIM: This study estimates the association between respondent and incident-level characteristics and informal payments. METHODS: A survey of 4218 households was conducted from November 2016 to February 2017. We analyzed healthcare incidents by all household members within the past four months. Multivariate negative binomial regression analysis was used to estimate the association between respondents and incident-level characteristics and informal OOP payments to providers. RESULTS: A total of 3494 healthcare incidents were reported by 3183 household-representatives. More-than-half (63 %) of all incidents involved informal activity (median=€150). About 30 % of those were related to provider requested payments. Using hospital, dental, diagnostic/screening, and emergency department services compared to primary care services and having oncological and surgical conditions were among the strongest predictors of higher rates for informal payments. The use of specific providers for reasons related to trust, reputation, referral, and lack of alternatives was also associated with higher rates of informal payments. Provider requested and skip the line payments were associated with larger OOP amounts compared to gratitude payments. CONCLUSION: This survey reveals that informal payments occur for higher-need and less cost-responsive healthcare services particularly in areas where patients lack alternatives. Health policy and regulatory interventions, including stricter control of the financial reporting system are essential to limit informal payments.

Prediction of Autoimmune Diseases by Targeted Metabolomic Assay of Urinary Organic Acids.

Autoimmune diseases (ADs) are chronic disorders characterized by the loss of self-tolerance, and although being heterogeneous, they share common pathogenic mechanisms. Self-antigens and inflammation markers are established diagnostic tools; however, the metabolic imbalances that underlie ADs are poorly described. The study aimed to employ metabolomics for the detection of disease-related changes in autoimmune diseases that could have predictive value. Quantitative analysis of 28 urine organic acids was performed using Gas Chromatography-Mass Spectrometry in a group of 392 participants. Autoimmune thyroiditis, inflammatory bowel disease, psoriasis and rheumatoid arthritis were the most prevalent autoimmune diseases of the study. Statistically significant differences were observed in the tricarboxylate cycle metabolites, succinate, methylcitrate and malate, the pyroglutamate and 2-hydroxybutyrate from the glutathione cycle and the metabolites methylmalonate, 4-hydroxyphenylpyruvate, 2-hydroxyglutarate and 2-hydroxyisobutyrate between the AD group and the control. Artificial neural networks and Binary logistic regression resulted in the highest predictive accuracy scores (66.7% and 74.9%, respectively), while Methylmalonate, 2-Hydroxyglutarate and 2-hydroxybutyrate were proposed as potential biomarkers for autoimmune diseases. Urine organic acid levels related to the mechanisms of energy production and detoxification were associated with the presence of autoimmune diseases and could be an adjunct tool for early diagnosis and prediction.

Real-world clinical outcome and toxicity data and economic aspects in patients with advanced breast cancer treated with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy: the experience of the Hellenic Cooperative Oncology Group.

BACKGROUND: We evaluated real-world clinical outcomes and toxicity data and assessed treatment-related costs in patients with advanced breast cancer who received treatment with cyclin-dependent kinase inhibitors (CDKi). PATIENTS AND METHODS: We conducted a prospective-retrospective analysis of patients with advanced hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer who received a CDKi, in combination with endocrine therapy, at any line of treatment. The primary endpoint was progression-free survival (PFS). Cost analysis was conducted from a public third-payer (National Organization for Healthcare Services Provision (EOPYY)) perspective, assessing only costs related to direct medical care, including drug therapy costs and adverse drug reaction (ADR)-related costs. RESULTS: From July 2015 to October 2019, 365 women received endocrine therapy combined with CDKi; median age was 61 years, postmenopausal 290 (80.6%) patients. CDKi were administered as first-line treatment in 149 (40.9%) patients, second-line treatment in 96 (26.4%) and third-line treatment and beyond in 119 (32.7%) patients. The most common adverse events were neutropenia, anaemia, thrombocytopenia and fatigue. Grade 3-4 adverse events occurred in 86 (23.6%) patients, whereas 8 (2.2%) patients permanently discontinued treatment due to toxicity. The median PFS for patients who received CDKi as first-line, second-line and third-line treatment and beyond was 18.7, 12 and 7.4 months, respectively. The median overall survival since the initiation of CDKi treatment was 29.9 months (95% CI: 23.0-not yet reached (NR)). The mean pharmaceutical therapy cost estimated per cycle was 2 724.12 € for each patient, whereas the main driver of the ADR-related costs was haematological adverse events. CONCLUSIONS: Treatment with CDKi was well tolerated, with a low drug discontinuation rate. Patients who received CDKi as first-line treatment had improved PFS and OS compared with second-line treatment and beyond. The main component of direct medical costs assessed in the cost analysis comprises CDKi pharmaceutical therapy costs. TRIAL REGISTRATION NUMBER: NCT04133207.

Medical decision making for patients with Parkinson disease under Average Cost Criterion.

Parkinson's disease (PD) is one of the most common disabling neurological disorders and results in substantial burden for patients, their families and the as a whole society in terms of increased health resource use and poor quality of life. For all stages of PD, medication therapy is the preferred medical treatment. The failure of medical regimes to prevent disease progression and to prevent long-term side effects has led to a resurgence of interest in surgical procedures. Partially observable Markov decision models (POMDPs) are a powerful and appropriate technique for decision making. In this paper we applied the model of POMDP's as a supportive tool to clinical decisions for the treatment of patients with Parkinson's disease. The aim of the model was to determine the critical threshold level to perform the surgery in order to minimize the total lifetime costs over a patient's lifetime (where the costs incorporate duration of life, quality of life, and monetary units). Under some reasonable conditions reflecting the practical meaning of the deterioration and based on the various diagnostic observations we find an optimal average cost policy for patients with PD with three deterioration levels.

Application of Economic Evaluation to Assess Feasibility for Reimbursement of Genomic Testing as Part of Personalized Medicine Interventions.

Background: The incorporation of genomic testing into clinical practice constitutes an opportunity to improve patients' lives, as it makes possible the implementation of innovative, individualized clinical interventions that maximize efficacy and/or minimize the risk of adverse drug reactions. In order to ensure equal access to genomic testing for all patients, the costs associated with these tests should be reimbursed by their respective national healthcare systems. Given that funding for the public health sector is decreasing in real terms, it is of paramount importance that the emerging interventions are thoroughly evaluated both in terms of their clinical effectiveness and their full economic cost. Objective: The aim of this study was to identify those genome-guided interventions that could be adopted and reimbursed by national healthcare systems. Further, we recorded the underlying factors determining the broad adoption of genome-guided interventions in clinical practice, in order to identify potential reimbursement criteria. Methods: We performed a systematic review of published (PubMed-listed) scientific articles on the economic evaluation of those individualized clinical interventions that include genomic tests. Information on genomic tests reimbursed by the US Medicare program was also included. Subsequently, we correlated the regulatory guidance given for the interventions collated in our systematic review with the corresponding economic evaluation results and policies of the Medicare program. Regulatory guidance information was collected from the PharmGKB online knowledgebase and the Clinical Pharmacogenetics Implementation Consortium (CPIC). Results: Most of the included studies constitute cost-utility analyses, in which the outcome of the interventions has been measured in quality-adjusted life years (QALYs) whereas an estimate of the total cost has been based upon direct medical cost data. Favorable economic evaluation results, as well as concrete evidence demonstrating the clinical utility of pre-emptive genotyping, are considered as prerequisites for the broad adoption and reimbursement of the costs incurred during genomic testing. Indicatively, pre-emptive HLA-B*5701 and TPMT testing before administration of abacavir and azathioprine, respectively, is reimbursed by Medicare based on both economic and efficacy evidence. Likewise, the medical necessary screening for MMR and BRCA1/2 genes are reimbursed for high-risk populations. Conclusions: Our findings further underline the need for further cost-utility analyses within different national healthcare systems, in order to promote the reimbursement of the cost of innovative genome-guided therapeutic interventions.

Cost-Effectiveness Analysis of Erenumab Versus OnabotulinumtoxinA for Patients with Chronic Migraine Attacks in Greece.

BACKGROUND: Migraine is a common, chronic neurovascular brain disorder with non-negligible multifaceted economic costs. Existing preventive treatments involve the selective use of onabotulinumtoxinA, which aims at migraine morbidity reduction for patients who have failed initial preventive treatment with oral agents. Erenumab is a new preventive treatment for migraines. OBJECTIVE: To evaluate the differences in costs and outcomes of the preventive treatment with erenumab versus onabotulinumtoxinA in patients with chronic migraines (CM) in Greece to assess the economic value of this treatment. METHODS: We conducted a cost-effectiveness analysis from both the payer and the societal perspective using a decision-tree analytic model. Outcomes were expressed in migraines avoided and in quality-adjusted life-years (QALYs). We obtained model inputs from the existing literature. The decision path adjusted for variation in the probability of adherence and the resulting differential effectiveness between the two treatments. Direct costs included the cost of the two drugs and administration costs, the costs of acute drugs used under usual care, and the costs of hospitalization, physician, and emergency department visits. Indirect costs for the societal perspective analyses included wages lost on workdays. The time-horizon of the analysis was 1 year and all costs were calculated in 2019 euros (€). Sensitivity analyses were conducted to control for parameter uncertainty and to evaluate the robustness of the findings. RESULTS: Our results indicate that treatment of CM with erenumab compared to onabotulinumtoxinA resulted in incremental cost-effectiveness ratios (ICERs) of €218,870 and €231,554 per QALY gained and €620 and €656 per migraine avoided, from the societal and the payer's perspective, respectively. Using a common cost-effectiveness threshold equal to three times the local gross domestic product (GDP) per capita (€49,000), for the erenumab ICERs to fall below this threshold, the erenumab price would have to be no more than €192 (societal perspective) or €173 (payer perspective). CONCLUSION: The prophylactic treatment of CM with erenumab in Greece might be cost effective compared to the existing alternative of onabotulinumtoxinA from both the payer and the societal perspective, but only at a highly discounted price. Nevertheless, erenumab could be considered a therapeutic option for patients who fail treatment with onabotulinumtoxinA.

eHealth Literacy: In the Quest of the Contributing Factors.

BACKGROUND: Understanding the factors that influence eHealth in a country is particularly important for health policy decision makers and the health care market, as it provides critical information to develop targeted and tailored interventions for relevant patient-consumer segments, and further suggests appropriate strategies for training the health illiterate part of the population. OBJECTIVE: The objective of the study is to assess the eHealth literacy level of Greek citizens, using the eHealth Literacy Scale (eHEALS), and further explore the factors that shape it and are associated with it. METHODS: This empirical study relies on a unique sample of 1064 citizens in Greece in the year 2013. The participants were requested to answer various questions about their ability to solve health-related issues using the Internet, and to provide information about their demographic characteristics and life-style habits. Ordered logit models were used to describe a certain citizen's likelihood of being eHealth literate. RESULTS: The demographic factors show that the probability of an individual being eHealth literate decreases by 23% (P=.001) when the individual ages and increases by 53% (P<.001) when he or she acquires higher level of education. Among the life-style variables, physical exercise appears to be strongly and positively associated with the level of eHealth literacy (P=.001). Additionally, other types of technology literacies, such as computer literacy and information literacy, further enhance the eHealth performance of citizens and have the greatest impact among all factors. CONCLUSIONS: The factors influencing eHealth literacy are complex and interdependent. However, the Internet is a disruptive factor in the relationship between health provider and health consumer. Further research is needed to examine how several factors associate with eHealth literacy, since, the latter is not only related to health care outcomes but also can be a tool for disseminating social inequalities.