Nikos Maniadakis

A randomized phase III study comparing three anthracycline-free taxane-based regimens, as first line chemotherapy, in metastatic breast cancer A Hellenic Cooperative Oncology Group study

Background Effective anthracycline-free combinations need to be evaluated in metastatic breast cancer (MBC), due to the increased number of patients treated with anthracycline-based adjuvant chemotherapy. Patients and methods Patients with MBC were randomized to paclitaxel and carboplatin (PCb) every 3 weeks or docetaxel and gemcitabine (GDoc) every 3 weeks or weekly paclitaxel (Pw). Trastuzumab was given to patients with HER-2 over-expressing tumors. The primary endpoint of the study was survival. Quality of life (QoL) and cost were assessed. Results Totally, 416 eligible patients entered the study. Median survival times were 29.9 months for PCb, 26.9 for GDoc and 41.0 for Pw (Pxa0=xa00.037). According to multivariate analysis, adjuvant chemotherapy, >1 metastatic sites, lack of maintenance hormonal therapy, and worse performance status (PS) were significant adverse prognostic factors for survival, while Pw when compared to GDoc improved survival (Pxa0=xa00.03), as well as when compared to PCb in the subgroup of patients with PSxa0=xa01 (Pxa0=xa00.01, treatment by PS interaction Pxa0=xa00.03). No significant differences in terms of time to progression were found. Severe myelotoxicity and mucositis were more frequent with GDoc, while severe neuropathy with PCb and Pw. QoL changes did not differ significantly between treatment groups, while cost analysis favored Pw. Conclusions Pw appears to be the most preferable choice among the 3 anthracycline-free taxanes-based regimens tested in the present study.

Economic evaluation of tiotropium and salmeterol in the treatment of chronic obstructive pulmonary disease (COPD) in Greece

ABSTRACT Objective: The objective of the study was to assess the cost-effectiveness of two therapeutic alternatives for chronic obstructive pulmonary disease in the Greek National Health Service (NHS) setting. Methods: A Markov probabilistic model was used to compare tiotropium with salmeterol. A Monte Carlo simulation with 5000 cases was run in the probabilistic analysis. The model was designed to compute the expected time spent in each state, the expected number of exacerbations occurring and the expected treatment cost per patient. Probabilities were extracted from clinical trials, resource utilisation and cost data from a Greek university hospital. Results: Quality adjusted life years were 0.70 (95% Uncertainty Interval [UI]: 0.63 to 0.77) in the tiotropium arm and 0.68 (95% UI: 0.60 to 0.75) in the salmeterol arm; a difference of 0.02 (95% UI: –0.08 to 0.13). Exacerbations reached 0.85 (95% UI: 0.80 to 0.91) in the tiotropium arm and 1.02 (95% UI: 0.84 to 1.21) in the salmeterol arm, a difference of –0.17 (95% UI: –0.37 to 0.02). Estimates of the mean annual cost per patient were €2504 (€2122 to €2965) in the tiotropium arm and €2655 (€2111 to €3324) in the salmeterol arm, a difference of –€151 (–€926 to €580). Stochastic analysis showed that tiotropium may have an advantage in reducing exacerbations. The probability that tiotropium is cost-effective was 65% at a ceiling value of €0 and reached 77% at a ceiling ratio of €1000. Results stay fairly constant in various sensitivity analyses. Conclusion: Even though tiotropium is more expensive to buy than salmeterol in the Greek NHS (using Greek costs there was no statistically significant difference in total costs between tiotropium and salmeterol), overall, during the course of a year, it is actually associated with a lower prevalence of exacerbations and lower treatment costs and thus may represent a viable and cost-effective alternative in the Greek NHS setting.

XELOX versus FOLFOX6 as an adjuvant treatment in colorectal cancer: an economic analysis

ABSTRACT Objectives: An economic analysis (based on interim data from a long-term, randomised, multi-centre, controlled, clinical trial) to evaluate chemotherapy with XELOX (capecitabine/oxaliplatin) versus FOLFOX6 (5Fluorouracil/leucovorin/oxaliplatin) as an adjuvant treatment for high risk colorectal cancer patients in Greece. Methods: As survival rate was the same in the two arms, a cost-minimisation analysis was carried out, from the perspectives of the National Health Service (NHS), Social Insurance Funds (SIF) and patients in Greece. Patient data were combined with 2008 unit prices to estimate the total cost of patient care, the patients’ travelling expenditure and their productivity losses. Raw data were bootstrapped 5000 times in order to allow statistical testing. Results: From an NHS perspective, the mean chemotherapy cost was €8762 with FOLFOX6 and €9713 with XELOX; costs of administration and hospitalisations were €5154 and €1050, respectively. Total treatment cost with FOLFOX6 reached €17u2009480 and with XELOX €12u2009525, a difference of €4955 (pu2009<u20090.001) in favour of the latter therapy. From an SIF perspective, the total cost of treatment was €16u2009240 with FOLFOX6 and €12u2009617 with XELOX, a reduction of €3623 (pu2009<u20090.001) with the latter therapy. Mean patient travelling cost was €184 with FOLFOX6 and €80 with XELOX, a difference of €104 (pu2009<u20090.001). Mean productivity loss was €100 with FOLFOX6 and €31 with XELOX, a difference of €69 (pu2009<u20090.001). Conclusions: Chemotherapy combining oral capecitabine and oxaliplatin reduces total treatment cost for the Greek National Health Service and Social Insurance Funds, mainly through a reduction in the cost of administration. From patients’ perspective, it reduces travelling expenditure and productivity losses. Therefore, this combination may be a cost-effective approach for the management of colorectal cancer patients who have had surgery in Greece. This is an analysis alongside a clinical trial, and should be interpreted in this specific context in which it was undertaken.

Physicians’ Perceptions and Adherence to Guidelines for the Management of Hypertension: A National, Multicentre, Prospective Study

Background. The aim of the current study was to investigate physicians perceptions and adherence to the European guidelines for the management of hypertension. Methods. This is a national, multicentre, prospective, observational study, conducted between November 2007 and June 2008, in Cyprus. Consecutive hypertensive patients have been recruited by a random sample of physicians. The physicians recommendations for every single patient have been recorded and compared with the 2007 ESH/ESC guidelines. Results. Of the total of 654 patients, 477 (72.9%) were correctly advised by their physician to receive antihypertensive treatment to control their blood pressure, while 396 (60.5%) correctly got advices to adopt only lifestyle changes. The overall adherence of physicians to the European guidelines (overall agreement rate) was 70.4% (k = 0.258, P < 0.001). Of the total of 68 physicians, 65 (95.6%) reported that they were aware of some guidelines. There was no statistically significant effect of specific physicians characteristics on the overall adherence to guidelines, but there was in the percentage of patients achieving medication guidelines. Conclusions. The study demonstrated that although Cypriot physicians declared that they were aware of the clinical guidelines for the management of hypertension, more than one-fourth of high risk hypertensive patients remained untreated and 40% of low risk patients received inappropriate medication.

Survival from breast cancer in relation to access to tertiary healthcare, body mass index, tumor characteristics and treatment: a Hellenic Cooperative Oncology Group (HeCOG) study.

Apart from tumour, treatment and patient characteristics at diagnosis, access to healthcare delivery may as well play a significant role in breast cancer prognosis. This study aimed to assess the additional impact exerted on survival by travel burden—a surrogate indicator of limited access to healthcare- expressed as geographical distance and/or time needed to reach the tertiary healthcare center from the patient’s residence. Between 1997 and 2005, 2,789 women participated in therapeutic clinical trials conducted by the Hellenic Cooperative Oncology Group. The effect of geographical distance and travel time between patient’s residence and treating hospital on survival was estimated using Cox proportional hazards regression adjusting for age, menopausal status, tumour size/grade, positive nodes (number), hormonal receptor status, HER2 overexpression, surgery type/treatment protocol as well as for body mass index >30xa0kg/m2. More aggressive tumour features, older treatment protocols and modifiable patient characteristics, such as obesity (HR: 1.27) adversely impacted on breast cancer survival. In addition, less studied indicators of access to healthcare, such as geographic distance >350xa0km and travel time >4xa0h were independently and significantly associated with worse outcomes (HRxa0=xa01.43 and 1.34 respectively). In conclusion, to address inequalities in breast cancer survival, improvements in access to healthcare services related to increased travel burden especially for patients of lower socioeconomic status should be considered, more than ever at times of financial crisis and independently of already known modifiable patient characteristics.

Economic evaluation of taxane-based first-line chemotherapy in the treatment of patients with metastatic breast cancer in Greece: an analysis alongside a multicenter, randomized phase III clinical trial.

BACKGROUNDnAn economic evaluation was undertaken alongside a randomized phase III trial comparing three regimens for metastatic breast cancer (MBC).nnnMATERIALS AND METHODSnTrial resource utilization and unit price data were combined to evaluate the cost of chemotherapy, concomitant medications, hospitalizations, diagnostic and laboratory tests. Treatment cost was combined with survival to estimate the incremental cost per life year saved. Quality-of-life data were used to estimate cost per quality-adjusted life year saved. Sensitivity analysis was used to compute results for various subgroups and for discounting cost and effects.nnnRESULTSnThe combination of gemcitabine (Gemzar, Eli Lilly, Indianapolis, USA) with docetaxel (Taxotere, Aventis Pharma, Dagenham, UK) (GDoc) is the least costly but least effective treatment. The combination of paclitaxel (Taxol) with carboplatin (Paraplatin, Bristol-Myers Squibb, Princeton, USA) is associated with higher cost and effectiveness compared with GDoc, while weekly paclitaxel (Pw), associated with the highest cost, is the most effective option. The incremental cost per life year saved of Pw versus GDoc was 3660 Euros (95% uncertainty interval dominance-9261). This result remained fairly constant in sensitivity analysis.nnnCONCLUSIONSnThe corresponding economic evaluation indicates that Pw represents an attractive treatment option for patients with MBC from an economic perspective in the context of the Greek National Health Service.

Economic Evaluation of Clopidogrel in Acute Coronary Syndrome Patients without ST-Segment Elevation in Greece

AbstractBackground: Current guidelines recommend treatment with antiplatelet and anticoagulant therapy for the secondary prevention of atherothrombotic events among patients with non-ST-segment elevation myocardial infarction (NSTEMI) or unstable angina (UA). The CURE (Clopidogrel in Unstable angina to prevent Recurrent Events) trial has shown that clopidogrel alone or in combination with aspirin is more effective in reducing the risk of atherothrombotic events than aspirin alone in NSTEMI or UA patients. However, in the current climate of financial constraints, the effectiveness of a treatment should be considered in conjunction with its long-term economic costs to determine the best possible care.n Objective: To evaluate the cost effectiveness of 1 year of treatment with clopidogrel in addition to aspirin in NSTEMI or UA patients from the third-party-payer perspective in Greece.n Methods: An existing Markov model consisting of six states (NSTEMI/UA/no event, first year with stroke, history of stroke, first year with myocardial infarction [MI], history of MI and death) was adapted and extended to the Greek healthcare setting for year 2012. Utility values obtained from a Greek national study were assigned to each health state in order to estimate the quality-adjusted life-years (QALYs). Costs assigned to each health state included antiplatelet treatment cost, cost for the management of adverse events and the costs for concomitant medication, hospitalization, outpatient visits, rehabilitation and nursing. Cost effectiveness and cost utility was expressed as the cost per life-year (LY) gained and QALY gained, respectively. A probabilistic sensitivity analysis was conducted.n Results: The Markov analysis predicts a discounted survival of 8.27 years in the aspirin treatment group and 8.41 years in the aspirin plus clopidogrel treatment group. The corresponding discounted QALYs were 6.88 and 7.00, respectively. The cumulated lifetime costs per patient were €18 779 and €19191, for the aspirin and aspirin plus clopidogrel treatment arms, respectively. The incremental cost-effectiveness ratio (ICER) with the addition of clopidogrel was €2951 for each LY saved and €3541 for each QALY saved. Finally, clopidogrel plus aspirin was found to be cost effective in more than 95% of simulated samples at a threshold of €7000 per discounted QALY gained.n Conclusion: One-year treatment with clopidogrel in addition to aspirin is a cost-effective treatment option for secondary prevention in patients with acute coronary syndrome without ST-segment elevation in Greece.

Economic evaluation of agomelatine relative to other antidepressants for treatment of major depressive disorders in Greece

BackgroundMajor depressive disorder (MDD) constitutes an important public health problem, as it is highly prevalent in the industrialized world and it is associated with substantial economic consequences for patients, health care providers, insurance and social security organizations and employers. To conduct an economic evaluation comparing agomelatine with other commonly used alternatives for treating patients with major depressive disorder (MDD) in Greece.MethodsAn existing international Markov model designed to evaluate the cost-effectiveness of agomelatine was adapted to the Greek setting. It reflects six different health states, in which patients may move on a monthly basis. The analysis was undertaken from a societal perspective. Transition probabilities, utilities and costs assigned to each health state were extracted from the published literature, government sources and expert opinion. Data reflects the year 2012 and was discounted using a rate of 3.5%. Probabilistic analysis was undertaken to deal with uncertainty.ResultsBase case analyses revealed that agomelatine is a dominant therapy for MDD relative to escitalopram, fluoxetine and sertraline, and it appeared to be cost-effective compared to venlafaxine (ICER: €547/QALY). Agomelatine remained a dominant treatment against generic sertraline and fluoxetine, and it appeared to be a cost-effective alternative compared to generic venlafaxine and escitalopram (ICER: €1,446/QALY and €3,303/QALY, respectively). Excluding the indirect cost from the analysis, agomelatine remained a cost-effective alternative over all comparators. In the probabilistic sensitivity analysis agomelatine was dominant in 44.5%, 89.6%, 70.6% and 84.6% of simulated samples against branded venlafaxine, escitalopram, fluoxetine and sertraline, respectively.ConclusionThe present evaluation indicates that agomelatine is either a dominant or a cost-effective alternative relative to branded or generic alternatives, in Greece.

Clopidogrel versus aspirin in patients with atherothrombosis: a CAPRIE-based cost-effectiveness model for Greece.

BACKGROUNDnAtherothrombosis represents a leading cause of morbidity and mortality worldwide. Given the prominent role of platelet aggregation in atherothrombosis, antiplatelet therapy forms the cornerstone of treatment, with proven efficacy in the secondary prevention of atherothrombotic events. Although clopidogrel seems to be superior to aspirin in terms of risk reduction for an atherothrombotic event, whether this clinical advantage is cost effective in Greece is unknown.nnnOBJECTIVEnThe aim of this study was to conduct a cost-effectiveness analysis comparing clopidogrel with aspirin in the secondary prevention of atherothrombotic events in patients with peripheral artery disease, a recent stroke or a recent myocardial infarction, from the third-party-payer perspective in Greece.nnnMETHODSnA Markov model with a 6-month cycle length was developed. Transition probabilities used in the model were obtained from the event rates reported in the CAPRIE trial. The effect of clopidogrel was applied only during the first 2 years of the model. Utility data were used to estimate quality-adjusted life-years (QALYs). Costs (for the year 2012) assigned to each health state included antiplatelet treatment cost, cost for the management of adverse events related to antiplatelet therapy and the direct healthcare cost of patients (i.e. concomitant medication, hospitalization, outpatient visits, rehabilitation, laboratory and imaging diagnostic examinations as well as interventions) in the acute and follow-up phase, separately. The incremental cost-effectiveness ratio (ICER) was calculated for life-years (LYs) and QALYs, separately. A probabilistic sensitivity analysis was conducted in order to evaluate the impact of the variation that characterizes the majority of model parameters to the cost-effectiveness results.nnnRESULTSnThe Markov analysis revealed that the discounted survival was 11.83 (95% CI 11.40, 12.22) years and 12.17 (95% CI 11.75, 12.55) years in the aspirin and clopidogrel treatment groups, respectively, a difference of 0.34 (95% CI 0.09, 0.618) LYs. The corresponding discounted QALYs were 8.63 (95% CI 8.34, 8.90) and 8.84 (95% CI 8.54, 9.10), respectively, a difference of 0.21 (95% CI 0.05, 0.37) QALYs. The cumulated lifetime costs per patient were €20 678 (95% CI 19 675, 21 724) and €21 688 (95% CI 20 649, 22 773), for aspirin and clopidogrel treatment arm, respectively. The ICER for clopidogrel was calculated to be €4038 (95% CI 2743, 7837) for each LY saved and €5518 (95% CI 3358, 12 921) for each QALY saved.nnnCONCLUSIONnThe analysis indicates that clopidogrel is cost effective for the secondary prevention of atherothrombotic events in the Greek setting. These findings are in line with those reported in other European countries.

Clopidogrel versus Aspirin in Patients with Atherothrombosis

AbstractBackground: Atherothrombosis represents a leading cause of morbidity and mortality worldwide. Given the prominent role of platelet aggregation in atherothrombosis, antiplatelet therapy forms the cornerstone of treatment, with proven efficacy in the secondary prevention of atherothrombotic events. Although clopidogrel seems to be superior to aspirin in terms of risk reduction for an atherothrombotic event, whether this clinical advantage is cost effective in Greece is unknown.n Objective: The aim of this study was to conduct a cost-effectiveness analysis comparing clopidogrel with aspirin in the secondary prevention of atherothrombotic events in patients with peripheral artery disease, a recent stroke or a recent myocardial infarction, from the third-party-payer perspective in Greece.n Methods: A Markov model with a 6-month cycle length was developed. Transition probabilities used in the model were obtained from the event rates reported in the CAPRIE trial. The effect of clopidogrel was applied only during the first 2 years of the model. Utility data were used to estimate quality-adjusted life-years (QALYs). Costs (for the year 2012) assigned to each health state included antiplatelet treatment cost, cost for the management of adverse events related to antiplatelet therapy and the direct healthcare cost of patients (i.e. concomitant medication, hospitalization, outpatient visits, rehabilitation, laboratory and imaging diagnostic examinations as well as interventions) in the acute and follow-up phase, separately. The incremental cost-effectiveness ratio (ICER) was calculated for life-years (LYs) and QALYs, separately. A probabilistic sensitivity analysis was conducted in order to evaluate the impact of the variation that characterizes the majority of model parameters to the cost-effectiveness results.n Results: The Markov analysis revealed that the discounted survival was 11.83 (95% CI 11.40, 12.22) years and 12.17 (95% CI 11.75, 12.55) years in the aspirin and clopidogrel treatment groups, respectively, a difference of 0.34 (95% CI 0.09, 0.618) LYs. The corresponding discounted QALYs were 8.63 (95% CI 8.34, 8.90) and 8.84 (95% CI 8.54, 9.10), respectively, a difference of 0.21 (95% CI 0.05, 0.37) QALYs. The cumulated lifetime costs per patient were €20 678 (95% CI 19 675, 21 724) and €21 688 (95% CI 20 649, 22 773), for aspirin and clopidogrel treatment arm, respectively. The ICER for clopidogrel was calculated to be €4038 (95% CI 2743, 7837) for each LY saved and €5518 (95% CI 3358, 12921) for each QALY saved.n Conclusion: The analysis indicates that clopidogrel is cost effective for the secondary prevention of atherothrombotic events in the Greek setting. These findings are in line with those reported in other European countries.