Vassilis Fragoulakis - Academia.edu (original) (raw)

Papers by Vassilis Fragoulakis

Follitropin Alpha for assisted reproduction: an analysis based on a non-interventional study in Greece

Current Medical Research and Opinion

The Pharmacogenomics Journal, 2019

Clopidogrel is an antiplatelet drug given to patients before and after having a percutaneous coro... more 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.

Economic Evaluation of Three Frequently Used Gonadotrophins in Assisted Reproduction Techniques in the Management of Infertility in the Netherlands

Applied Health Economics and Health Policy, 2016

Background and ObjectiveSubfertility represents a multidimensional problem associated with signif... more Background and ObjectiveSubfertility represents a multidimensional problem associated with significant distress and impaired social well-being. In the Netherlands, an estimated 50,000 couples visit their general practitioner and 30,000 couples seek medical specialist care for subfertility. We conducted an economic evaluation comparing recombinant human follicle-stimulating hormone (follitropin alfa, r-hFSH, Gonal-F®) with two classes of urinary gonadotrophins—highly purified human menopausal gonadotrophin (hp-HMG, Menopur®) and urinary follicle-stimulating hormone (uFSH, Fostimon®)—for ovarian stimulation in women undergoing in vitro fertilization (IVF) treatment in the Netherlands.MethodsA pharmacoeconomic model was developed, simulating each step in the IVF protocol from the start of therapy until either a live birth, a new IVF treatment cycle or cessation of IVF, following a long down-regulation protocol. A decision tree combined with a Markov model details progress through each health state, including ovum pickup, fresh embryo transfer, up to two subsequent cryo-preserved embryo transfers, and (ongoing) pregnancy or miscarriage. A health insurer perspective was chosen, and the time horizon was set at a maximum of three consecutive treatment cycles, in accordance with Dutch reimbursement policy. Transition probabilities and costing data were derived from a real-world observational outcomes database (from Germany) and official tariff lists (from the Netherlands). Adverse events were considered equal among the comparators and were therefore excluded from the economic analysis. A Monte Carlo simulation of 5000 iterations was undertaken for each strategy to explore uncertainty and to construct uncertainty intervals (UIs). All cost data were valued in 2013 Euros. The model’s structure, parameters and assumptions were assessed and confirmed by an external clinician with experience in health economics modelling, to inform on the appropriateness of the outcomes and the applicability of the model in the chosen setting.ResultsThe mean total treatment costs were estimated as €5664 for follitropin alfa (95 % UI €5167–6151), €5990 for hp-HMG (95 % UI €5498–6488) and €5760 for uFSH (95 % UI €5256–6246). The probability of a live birth was estimated at 36.1 % (95 % UI 27.4–44.3 %), 33.9 % (95 % UI 26.2–41.5 %) and 34.1 % (95 % UI 25.9–41.8 %) for follitropin alfa, hp-HMG and uFSH, respectively. The costs per live birth estimates were €15,674 for follitropin alfa, €17,636 for hp-HMG and €16,878 for uFSH. Probabilistic sensitivity analysis indicated a probability of 72.5 % that follitropin alfa is cost effective at a willingness to pay of €20,000 per live birth. The probabilistic results remained constant under several analyses.ConclusionThe present analysis shows that follitropin alfa may represent a cost-effective option in comparison with uFSH and hp-HMG for IVF treatment in the Netherlands healthcare system.

International Journal of Reliable and Quality E-Healthcare, 2014

Cervical cancer is the malignancy most succesfully monitored by screening programs. Although most... more Cervical cancer is the malignancy most succesfully monitored by screening programs. Although most counties offer screening services, outcomes differ. It is clear that incidence reduction is achieved when quality assurance is implemented. Quality indicators are essential audit tools when implementing screening policies. Uniform indicators are used to monitor general performance and to identify potential problems that may occur and jeopardise efforts. That way quality management is enabled and the assessment of deviation from goals is facilitated. In this paper the authors present the workflow of cervical cancer screening programs in respect to the quality and performance indicators required by the European Guidelines for Quality Assurance in Cervical Cancer Screening. The authors also propose the appropriate data structures and entities that are required for a computerised system to support their calculation. Additionally the authors highlight important interconnections of the comput...

Value in Health, 2014

MCID: 40.7% and 41.0%). Similar improvements were observed with both dosing regimens and in patie... more MCID: 40.7% and 41.0%). Similar improvements were observed with both dosing regimens and in patients with or without prior anti-TNF exposure. Correlations were observed between improvements in PROs and DAS28 (data not shown). ConClusions: Improvements observed to Wk24 in generic and diseasespecific PROs were sustained to Wk96 of the RAPID-PsA trial for both CZP dosing regimens.

International Journal of Reliable and Quality E-Healthcare, 2014

The aim of the present study is to provide an overview of recent reforms in Greece as imposed by ... more The aim of the present study is to provide an overview of recent reforms in Greece as imposed by the fiscal adjustments. Potential harmful consequences of these vast healthcare reforms are also discussed, as a collateral victim of the recession, in which case the real “patient” is the overall healthcare system. Based on an extended review of the related literature, the economic crisis, currently numbering five years in Greece, was accompanied by vast healthcare reforms and significant cuts in spending. In particular, austerity measures implemented, impose that health expenditure should not exceed 6% as a share of GDP. Savings were expected to be accomplished through vast changes, including the redetermination of both pharmaceutical reimbursement and pricing, reduction of public servants and cost containment regarding payments to the private sector. So far, there is a significant rise in demand for public hospital services, following a significant drop for private providers, includin...

Clinical therapeutics, 2014

The goal of this study was to estimate the cost of production of 1 unit of blood from a National ... more The goal of this study was to estimate the cost of production of 1 unit of blood from a National Health Service perspective in Greece. In agreement with guidelines, the cost of blood production in this study accounted only for the resources expended for collection, processing, laboratory testing, and storage. Hence, the costs associated with donor recruitment, pretransfusion preparation, transfusion administration, follow-up management of adverse events, and other long-term relevant costs were not taken into consideration. The indirect cost of blood donations for donors (productivity loss) was also considered. A questionnaire was used to collect data regarding personnel time, annual blood quantities collected, percentage of wastage, utilization of consumables, institutional overhead, information technology expenditure, medical equipment utilized, nuclear acid tests, and other factors. Data gathered by 53 hospitals across the country were assessed. A model was constructed with econom...

Value in Health, 2010

A399 811). Other costs included consultations (c54, c63, c64, c58) and examinations (c19, c26, c2... more A399 811). Other costs included consultations (c54, c63, c64, c58) and examinations (c19, c26, c26, c26). Factors predicting high cost (R 2 = 0.6426) were the number of hospital interventions, treatment switches, disease state changes, current disease state and issues with ocular burning, stinging or aching affecting daily activities. For glaucoma patients having 0, 1, 2 or ≥3 treatment switches this gave total costs of c273 ± 108, c320 ± 231, c511 ± 462 and c932 ± 950, respectively. Medication costs were c177, c187, c268 and c368, and interventional procedure costs were c0, c50, c166 and c478, respectively. CONCLUSIONS: Glaucoma treatments (medication and interventional procedures) are the key cost drivers in management of glaucoma in Germany. Avoiding treatment switches, disease progression and interventional procedures should have an impact on the cost of glaucoma care.

Value in Health, 2010

A357 to the cost-effective use of appropriate drugs in managing chronic disease. The project high... more A357 to the cost-effective use of appropriate drugs in managing chronic disease. The project highlighted how countries with relevant experience in evidence-informed policy making in health care can assist others in strengthening their decision-making systems.

Value in Health, 2008

To develop an epidemiological and economic model of first-onset cardiovascular disease (CVD, comp... more To develop an epidemiological and economic model of first-onset cardiovascular disease (CVD, comprising myocardial infarction and ischemic stroke) in Korea that can be applied to cost-effectiveness analyses of interventions. METHODS: KIMCHI is a Markov model with yearly cycles and the health states 'Alive without CVD', 'Alive with CVD', 'Dead from CVD' and 'Dead from non-CVD causes'. It is populated with 5270 CVD-naïve subjects aged Ն18 years from the 2005 Korea National Health and Nutritional Examination Survey. Annual probabilities of CVD are estimated for each individual using the Asian-specific risk equation by Wu, the covariates for which are: sex, age, total cholesterol (TC), systolic blood pressure (SBP), smoking, diabetes and body mass index (BMI). Ageand-sex-specific annual probabilities of death are based on national health data. To illustrate the function of KIMCHI, follow-up was simulated of Koreans aged Ն55 years until death or age 99 and the cost-effectiveness of atorvastatin for the primary prevention of CVD assessed using decision analysis. The TC-reducing efficacy and cost of atorvastatin were drawn from a meta-analysis and current drug pricing schedules, respectively. CVD costs were provided by the Korean Health Insurance Review and Assessment Services. A 5% annual discount rate was applied. RESULTS: KIMCHI predicted that 30.4% and 18.2% of CVD-naïve Koreans currently aged Ն55 years will develop non-fatal and fatal CVD, respectively, by age 99. Atorvastatin was predicted to reduce these figures to 25.4% and 15.4%, corresponding to numbers needed to treat of 20 and 36 to prevent non-fatal and fatal CVD, respectively. The estimated ICERs were 21.8 million KW/YoLS and 17.4 million KW/QALY saved. CONCLUSIONS: KIMCHI is a contemporary epidemiological and economic model of CVD in Korea that can predict future patterns of disease and be applied to cost-effectiveness analyses of interventions that alter any of TC, SBP, smoking, diabetes and BMI.

Value in Health, 2006

METHODS: A total of 361 patients with AF (mean age 71 ± 9, 61% male) in 45 physician practices th... more METHODS: A total of 361 patients with AF (mean age 71 ± 9, 61% male) in 45 physician practices throughout Germany were recruited. 3-month retrospective and 6-month prospective clinical data including INR values and anticoagulation strategy were obtained from the physician chart through standardised questionnaire. Patient health-related and disease-specific quality of life was assessed with the SF-36 and MacNew heart disease instruments. The patient completed a standardised questionnaire at three and six months, which documented hospitalisations, medications, and complications, as well as quality of life, patient satisfaction and compliance. Three hundred-four (84%) patients completed the entire study. RESULTS: Of all patients, 90% had been treated with VKAs at some time since AF-diagnosis, 88% were still on treatment. 10% of the patients received aspirin as their anticoagulation therapy. INR was measured at least once a month in over 70% of the patients. INR values were 56% of the time within, 14% below and 30% over the target range. SF-36 results were similar to patients of comparable age and health. Fifty-five percent of patients reported they were always or mostly satisfied with their treatment and 66% stated they complied with their prescribed treatment most or all of the time. CONCLUSIONS: This study presents German "real-life" data in treating patients with AF and identifies the potential to advance the quality of care particularly with respect to anticoagulation.

Lung Cancer: Targets and Therapy, 2012

An economic evaluation was conducted in conjunction with a prospective, multicenter, randomized t... more An economic evaluation was conducted in conjunction with a prospective, multicenter, randomized trial, to compare pemetrexed with erlotinib in pretreated patients with metastatic non-small cell lung cancer (NSCLC) in Greece. Methods: The effectiveness of treatments examined was comparable; thus, cost minimization analysis was conducted to evaluate which option is less costly. Patient-level resource utilization data were combined with unit cost data, which were aggregated to compute the total treatment cost for each patient. The analysis was conducted with respect to the individual incurring the cost. Due to the limited life-expectancy of the patients, discounting was unnecessary. Since data were right censored, the Bang and Tsiatis method was employed to identify unbiased estimators of the mean cost per treatment arm, while other methods were employed for sensitivity analysis. To analyze uncertainty and to construct uncertainty intervals (UI), stochastic analysis was performed based on 5000 bootstrap replications. Results: The one-year survival rate was 28.3% in the pemetrexed arm and 31.7% in the erlotinib arm, while the corresponding median survival over the follow-up period was 7.1 and 6.7 months, respectively (P = 0.765). Total cost in the pemetrexed arm was €10508 (95% UI: €9552-€11488), while in the erlotinib arm the cost was €9563 (95% UI: €8499-€10711); thus, no statistically significant difference was found between the comparators (P = 0.206). Results remained constant for all sensitivity analyses. Conclusions: There is no survival or cost difference between erlotinib and pemetrexed; thus, these therapies are equivalent. Further studies are needed to determine whether other parameters, such as quality of life, differ among treatment options.

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

Current Medical Research and Opinion, 2006

The objective of the study was to assess the cost-effectiveness of two therapeutic alternatives f... more 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. 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. 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 euro2504 (euro2122 to euro2965) in the tiotropium arm and euro2655 (euro2111 to euro3324) in the salmeterol arm, a difference of -euro151 (-euro926 to euro580). 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 euro0 and reached 77% at a ceiling ratio of euro1000. Results stay fairly constant in various sensitivity analyses. 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.

Cost-Minimization Analysis of the Treatment of Patients With Metastatic Colorectal Cancer in Greece

Clinical Therapeutics, 2012

In 2008, colorectal cancer was the fourth most common cause of cancer-related death worldwide. Mo... more In 2008, colorectal cancer was the fourth most common cause of cancer-related death worldwide. Monotherapy with monoclonal antibodies directed against the epidermal growth factor receptor, such as cetuximab and panitumumab, has recently been introduced in the management of metastatic colorectal cancer (mCRC) patients. The aim of this study was to conduct a cost-minimization analysis comparing panitumumab with cetuximab in the treatment of patients with epidermal growth factor receptor-expressing mCRC with nonmutated (wild-type) Kirsten rat sarcoma viral oncogene homolog in Greece. The perspective of analysis was that of payers (Social Security Sickness Fund) and the country's National Health Service (NHS). The model was designed to contain probabilistic parameters to account for uncertainty and variation in these parameters. All resources consumed in local hospitals in the management of patients in each case were evaluated. Two analyses were performed: 1 evaluating cost per milligram and another evaluating cost per vial. From a payer perspective, the mean 20-week total cost per patient for panitumumab and cetuximab was: (1) per-milligram analysis: €16,349 and €18,242, respectively; and (2) per-vial analysis: €18,808 and €19,701. From the NHS perspective, the mean total costs per patient were slightly higher; however, the use of panitumumab was associated with a 17.7% and 12.4% cost reduction in per-milligram and per-vial analysis, respectively. The results of probabilistic models confirmed those of the deterministic analyses. In the Greek NHS and Social Security Sickness Fund setting, panitumumab monotherapy potentially constitutes a cost-saving option (versus cetuximab monotherapy) in the management of patients with mCRC and no mutation of Kirsten rat sarcoma viral oncogene homolog.

Cancer Management and Research, 2013

Background: Multiple myeloma is a hematologic malignancy that incurs a substantial economic burde... more Background: Multiple myeloma is a hematologic malignancy that incurs a substantial economic burden in care management. Since most patients with multiple myeloma eventually relapse or become refractory to current therapies (rrMM), the aim of this study was to assess the costeffectiveness of the combination of lenalidomide-dexamethasone, relative to bortezomib alone, in patients suffering from rrMM in Greece. Methods: An international discrete event simulation model was locally adapted to estimate differences in overall survival and treatment costs associated with the two alternative treatment options. The efficacy data utilized came from three international trials (MM-009, MM-010, APEX). Quality of life data were extracted from the published literature. Data on resource use and prices came from relevant local sources and referred to 2012. The perspective of the analysis was that of public providers. Total costs for monitoring and administration of therapy to patients, management of adverse events, and cost of medication were captured. A 3.5% discount rate was used for costs and health outcomes. A Monte Carlo simulation was used to estimate probabilistic results with 95% uncertainty intervals (UI) and a cost-effectiveness acceptability curve. Results: The mean number of quality-adjusted life years (QALYs) was 3.01 (95% UI 2.81-3.20) and 2.22 (95% UI 2.02-2.41) for lenalidomide-dexamethasone and bortezomib, respectively, giving an incremental gain of 0.79 (95% UI 0.49-1.06) QALYs in favor of lenalidomide-dexamethasone. The mean cost of therapy per patient was estimated at €77,670 (95% UI €76,509-€78,900) and €48,928 (95% UI €48,300-€49,556) for lenalidomidedexamethasone and bortezomib, respectively. The incremental cost per life year gained with lenalidomide-dexamethasone was estimated at €29,415 (95% UI €23,484-€37,583) and the incremental cost per QALY gained at €38,268 (95% UI €27,001-€58,065). The probability of lenalidomide-dexamethasone being a cost-effective therapy option at a threshold three times the per capita income (€60,000 per QALY) was higher than 95%. The results remained constant, without altering the conclusions, under several hypothetical scenarios. Conclusion: The combination of lenalidomide and dexamethasone may represent a costeffective choice relative to bortezomib monotherapy for patients in Greece with previously treated multiple myeloma.

Clopidogrel versus Aspirin in Patients with Atherothrombosis

Applied Health Economics and Health Policy, 2012

Atherothrombosis represents a leading cause of morbidity and mortality worldwide. Given the promi... more 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. 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. 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. 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, 12 921) for each QALY saved. 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.

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

Applied Health Economics and Health Policy, 2012

Current guidelines recommend treatment with antiplatelet and anticoagulant therapy for the second... more 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. 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. 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. 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 € 19 191, for the aspirin and aspirin plus clopidogrel treatment arms, respectively. The incremental cost-effectiveness ratio (ICER) with the addition of clopidogrel was &U20AC;2951 for each LY saved and &U20AC;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 &U20AC;7000 per discounted QALY gained. 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.

ClinicoEconomics and Outcomes Research, 2013

To quantify the economic effects of a child conceived by in vitro fertilization (IVF) in terms of... more To quantify the economic effects of a child conceived by in vitro fertilization (IVF) in terms of net tax revenue from the state's perspective in Greece. Methods: Based on previous international experience, a mathematical model was developed to assess the lifetime productivity of a single individual and his/her lifetime transactions with governmental agencies. The model distinguished among three periods in the economic life cycle of an individual: (1) early life, when the government primarily contributes resources through child tax credits, health care, and educational expenses; (2) employment, when individuals begin returning resources through taxes; and (3) retirement, when the government expends additional resources on pensions and health care. The cost of a live birth with IVF was based on the modification of a previously published model developed by the authors. All outcomes were discounted at a 3% discount rate. The data inputs-namely, the economic or demographic variables-were derived from the National Statistical Secretariat of Greece and other relevant sources. To deal with uncertainty, bias-corrected uncertainty intervals (UIs) were calculated based on 5000 Monte Carlo simulations. In addition, to examine the robustness of our results, other one-way sensitivity analyses were also employed. Results: The cost of IVF per birth was estimated at €17,015 (95% UI: €13,932-€20,200). The average projected income generated by an individual throughout his/her productive life was €258,070 (95% UI: €185,376-€339,831). In addition, his/her life tax contribution was estimated at €133,947 (95% UI: €100,126-€177,375), while the discounted governmental expenses for elderly and underage individuals were €67,624 (95% UI: €55,211-€83,930). Hence, the net present value of IVF was €60,435 (95% UI: €33,651-€94,330), representing a 182% net return on investment. Results remained constant under various assumptions for the main model parameters. Conclusion: State-funded IVF may represent good value for money in the Greek setting, since it has positive tax benefits for the government, notwithstanding its beneficial psychological effect on infertile couples.

ClinicoEconomics and Outcomes Research, 2015

We aimed to estimate the total mean annual treatment cost of different therapy options for patien... more We aimed to estimate the total mean annual treatment cost of different therapy options for patients with moderate-to-severe rheumatoid arthritis (RA) in Greece. Methods: A cost-minimization approach was adopted. An economic model was developed to estimate the direct costs of the three widely used treatments within a 1-year time horizon, from a health care payer perspective, either for new or for existing patients. Data on resource use, dose escalation, and frequency of therapy were based on a nationwide field survey of rheumatologists. Other analyses were also undertaken based on evidence from the literature. Total cost comprised the cost of drugs, administration, and hospital day care visits. Unit cost data were obtained from the price bulletin and the government gazettes issued by the Ministry of Health. Due to the short time horizon of the study, the cost was not discounted. Results: The mean annual total cost per new (or per existing) responder patient on etanercept was estimated at €9,845 (€9,840), and the total cost on etanercept/methotrexate (MTX) was estimated at €9,857 (€9,852). Therapy with etanercept had lower annual cost relative to adalimumab and infliximab. On an annual basis, it was estimated that the difference between etanercept monotherapy and adalimumab monotherapy was €544 (€1,323). Similarly, the difference between etanercept/MTX and infliximab/MTX was €1,871 (€1,490) and €543 (€1,323), respectively, relative to adalimumab/MTX. Results remained constant under other scenario analyses undertaken. Conclusion: In the real-life practice setting in Greece, where dose intensity and frequency differences occur, etanercept alone or in combination with MTX, if prescribed as per label, represents the option with lower annual cost per patient when compared with adalimumab or infliximab in patients with RA. These results hold true as long as the assumptions and data used in the analysis remain stable and may alter if any of the underlying parameters, such as drug price, change.

ClinicoEconomics and Outcomes Research, 2012

Background: The purpose of this study was to compare Gonal-F ® , a recombinant follicle-stimulati... more Background: The purpose of this study was to compare Gonal-F ® , a recombinant follicle-stimulating hormone, with Menopur ® , a highly purified human menopausal gonadotrophin (hpHMG) in assisted reproduction in Greece. Methods: A decision tree in combination with a Markov model was used to assess the clinical and economical impact of comparators for up to three consecutive cycles. Transition probabilities were derived from the literature and validated by clinical experts. Cost components were derived from the electronic databases of selected private and public clinics. A probabilistic sensitivity analysis was performed to deal with uncertainty and to construct a cost-effectiveness acceptability curve. Results: There was a statistically significant difference in favor of the recombinant folliclestimulating hormone arm compared with hpHMG, which was associated with 52 more births (95% uncertainty interval 26-78, P = 0.001) per 1000 patients. The cost per birth was estimated at €16,906 and €17,286 in the recombinant follicle-stimulating hormone and hpHMG arms, respectively. The cost per in vitro fertilization was estimated at €4365 in the recombinant folliclestimulating hormone arm and €3815 in the hpHMG arm, indicating a difference of €550. The incremental cost per birth for recombinant follicle-stimulating hormone versus hpHMG was estimated at €14,540, while the incremental cost per life-year was estimated at €175.41. Conclusion: Recombinant follicle-stimulating hormone may represent a cost-effective choice compared with hpHMG when used for ovarian stimulation for a pharmacoeconomic point of view in the Greek public health care setting. However, it must be noted that in clinical practice both agents may be used together to increase the number of follicles, oocytes, embryos, and/or pregnancies in treated patients, an approach which has not been evaluated in Greece or reported in the literature due to obvious limitations.

Follitropin Alpha for assisted reproduction: an analysis based on a non-interventional study in Greece

Current Medical Research and Opinion

The Pharmacogenomics Journal, 2019

Clopidogrel is an antiplatelet drug given to patients before and after having a percutaneous coro... more 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.

Economic Evaluation of Three Frequently Used Gonadotrophins in Assisted Reproduction Techniques in the Management of Infertility in the Netherlands

Applied Health Economics and Health Policy, 2016

Background and ObjectiveSubfertility represents a multidimensional problem associated with signif... more Background and ObjectiveSubfertility represents a multidimensional problem associated with significant distress and impaired social well-being. In the Netherlands, an estimated 50,000 couples visit their general practitioner and 30,000 couples seek medical specialist care for subfertility. We conducted an economic evaluation comparing recombinant human follicle-stimulating hormone (follitropin alfa, r-hFSH, Gonal-F®) with two classes of urinary gonadotrophins—highly purified human menopausal gonadotrophin (hp-HMG, Menopur®) and urinary follicle-stimulating hormone (uFSH, Fostimon®)—for ovarian stimulation in women undergoing in vitro fertilization (IVF) treatment in the Netherlands.MethodsA pharmacoeconomic model was developed, simulating each step in the IVF protocol from the start of therapy until either a live birth, a new IVF treatment cycle or cessation of IVF, following a long down-regulation protocol. A decision tree combined with a Markov model details progress through each health state, including ovum pickup, fresh embryo transfer, up to two subsequent cryo-preserved embryo transfers, and (ongoing) pregnancy or miscarriage. A health insurer perspective was chosen, and the time horizon was set at a maximum of three consecutive treatment cycles, in accordance with Dutch reimbursement policy. Transition probabilities and costing data were derived from a real-world observational outcomes database (from Germany) and official tariff lists (from the Netherlands). Adverse events were considered equal among the comparators and were therefore excluded from the economic analysis. A Monte Carlo simulation of 5000 iterations was undertaken for each strategy to explore uncertainty and to construct uncertainty intervals (UIs). All cost data were valued in 2013 Euros. The model’s structure, parameters and assumptions were assessed and confirmed by an external clinician with experience in health economics modelling, to inform on the appropriateness of the outcomes and the applicability of the model in the chosen setting.ResultsThe mean total treatment costs were estimated as €5664 for follitropin alfa (95 % UI €5167–6151), €5990 for hp-HMG (95 % UI €5498–6488) and €5760 for uFSH (95 % UI €5256–6246). The probability of a live birth was estimated at 36.1 % (95 % UI 27.4–44.3 %), 33.9 % (95 % UI 26.2–41.5 %) and 34.1 % (95 % UI 25.9–41.8 %) for follitropin alfa, hp-HMG and uFSH, respectively. The costs per live birth estimates were €15,674 for follitropin alfa, €17,636 for hp-HMG and €16,878 for uFSH. Probabilistic sensitivity analysis indicated a probability of 72.5 % that follitropin alfa is cost effective at a willingness to pay of €20,000 per live birth. The probabilistic results remained constant under several analyses.ConclusionThe present analysis shows that follitropin alfa may represent a cost-effective option in comparison with uFSH and hp-HMG for IVF treatment in the Netherlands healthcare system.

International Journal of Reliable and Quality E-Healthcare, 2014

Cervical cancer is the malignancy most succesfully monitored by screening programs. Although most... more Cervical cancer is the malignancy most succesfully monitored by screening programs. Although most counties offer screening services, outcomes differ. It is clear that incidence reduction is achieved when quality assurance is implemented. Quality indicators are essential audit tools when implementing screening policies. Uniform indicators are used to monitor general performance and to identify potential problems that may occur and jeopardise efforts. That way quality management is enabled and the assessment of deviation from goals is facilitated. In this paper the authors present the workflow of cervical cancer screening programs in respect to the quality and performance indicators required by the European Guidelines for Quality Assurance in Cervical Cancer Screening. The authors also propose the appropriate data structures and entities that are required for a computerised system to support their calculation. Additionally the authors highlight important interconnections of the comput...

Value in Health, 2014

MCID: 40.7% and 41.0%). Similar improvements were observed with both dosing regimens and in patie... more MCID: 40.7% and 41.0%). Similar improvements were observed with both dosing regimens and in patients with or without prior anti-TNF exposure. Correlations were observed between improvements in PROs and DAS28 (data not shown). ConClusions: Improvements observed to Wk24 in generic and diseasespecific PROs were sustained to Wk96 of the RAPID-PsA trial for both CZP dosing regimens.

International Journal of Reliable and Quality E-Healthcare, 2014

The aim of the present study is to provide an overview of recent reforms in Greece as imposed by ... more The aim of the present study is to provide an overview of recent reforms in Greece as imposed by the fiscal adjustments. Potential harmful consequences of these vast healthcare reforms are also discussed, as a collateral victim of the recession, in which case the real “patient” is the overall healthcare system. Based on an extended review of the related literature, the economic crisis, currently numbering five years in Greece, was accompanied by vast healthcare reforms and significant cuts in spending. In particular, austerity measures implemented, impose that health expenditure should not exceed 6% as a share of GDP. Savings were expected to be accomplished through vast changes, including the redetermination of both pharmaceutical reimbursement and pricing, reduction of public servants and cost containment regarding payments to the private sector. So far, there is a significant rise in demand for public hospital services, following a significant drop for private providers, includin...

Clinical therapeutics, 2014

The goal of this study was to estimate the cost of production of 1 unit of blood from a National ... more The goal of this study was to estimate the cost of production of 1 unit of blood from a National Health Service perspective in Greece. In agreement with guidelines, the cost of blood production in this study accounted only for the resources expended for collection, processing, laboratory testing, and storage. Hence, the costs associated with donor recruitment, pretransfusion preparation, transfusion administration, follow-up management of adverse events, and other long-term relevant costs were not taken into consideration. The indirect cost of blood donations for donors (productivity loss) was also considered. A questionnaire was used to collect data regarding personnel time, annual blood quantities collected, percentage of wastage, utilization of consumables, institutional overhead, information technology expenditure, medical equipment utilized, nuclear acid tests, and other factors. Data gathered by 53 hospitals across the country were assessed. A model was constructed with econom...

Value in Health, 2010

A399 811). Other costs included consultations (c54, c63, c64, c58) and examinations (c19, c26, c2... more A399 811). Other costs included consultations (c54, c63, c64, c58) and examinations (c19, c26, c26, c26). Factors predicting high cost (R 2 = 0.6426) were the number of hospital interventions, treatment switches, disease state changes, current disease state and issues with ocular burning, stinging or aching affecting daily activities. For glaucoma patients having 0, 1, 2 or ≥3 treatment switches this gave total costs of c273 ± 108, c320 ± 231, c511 ± 462 and c932 ± 950, respectively. Medication costs were c177, c187, c268 and c368, and interventional procedure costs were c0, c50, c166 and c478, respectively. CONCLUSIONS: Glaucoma treatments (medication and interventional procedures) are the key cost drivers in management of glaucoma in Germany. Avoiding treatment switches, disease progression and interventional procedures should have an impact on the cost of glaucoma care.

Value in Health, 2010

A357 to the cost-effective use of appropriate drugs in managing chronic disease. The project high... more A357 to the cost-effective use of appropriate drugs in managing chronic disease. The project highlighted how countries with relevant experience in evidence-informed policy making in health care can assist others in strengthening their decision-making systems.

Value in Health, 2008

To develop an epidemiological and economic model of first-onset cardiovascular disease (CVD, comp... more To develop an epidemiological and economic model of first-onset cardiovascular disease (CVD, comprising myocardial infarction and ischemic stroke) in Korea that can be applied to cost-effectiveness analyses of interventions. METHODS: KIMCHI is a Markov model with yearly cycles and the health states 'Alive without CVD', 'Alive with CVD', 'Dead from CVD' and 'Dead from non-CVD causes'. It is populated with 5270 CVD-naïve subjects aged Ն18 years from the 2005 Korea National Health and Nutritional Examination Survey. Annual probabilities of CVD are estimated for each individual using the Asian-specific risk equation by Wu, the covariates for which are: sex, age, total cholesterol (TC), systolic blood pressure (SBP), smoking, diabetes and body mass index (BMI). Ageand-sex-specific annual probabilities of death are based on national health data. To illustrate the function of KIMCHI, follow-up was simulated of Koreans aged Ն55 years until death or age 99 and the cost-effectiveness of atorvastatin for the primary prevention of CVD assessed using decision analysis. The TC-reducing efficacy and cost of atorvastatin were drawn from a meta-analysis and current drug pricing schedules, respectively. CVD costs were provided by the Korean Health Insurance Review and Assessment Services. A 5% annual discount rate was applied. RESULTS: KIMCHI predicted that 30.4% and 18.2% of CVD-naïve Koreans currently aged Ն55 years will develop non-fatal and fatal CVD, respectively, by age 99. Atorvastatin was predicted to reduce these figures to 25.4% and 15.4%, corresponding to numbers needed to treat of 20 and 36 to prevent non-fatal and fatal CVD, respectively. The estimated ICERs were 21.8 million KW/YoLS and 17.4 million KW/QALY saved. CONCLUSIONS: KIMCHI is a contemporary epidemiological and economic model of CVD in Korea that can predict future patterns of disease and be applied to cost-effectiveness analyses of interventions that alter any of TC, SBP, smoking, diabetes and BMI.

Value in Health, 2006

METHODS: A total of 361 patients with AF (mean age 71 ± 9, 61% male) in 45 physician practices th... more METHODS: A total of 361 patients with AF (mean age 71 ± 9, 61% male) in 45 physician practices throughout Germany were recruited. 3-month retrospective and 6-month prospective clinical data including INR values and anticoagulation strategy were obtained from the physician chart through standardised questionnaire. Patient health-related and disease-specific quality of life was assessed with the SF-36 and MacNew heart disease instruments. The patient completed a standardised questionnaire at three and six months, which documented hospitalisations, medications, and complications, as well as quality of life, patient satisfaction and compliance. Three hundred-four (84%) patients completed the entire study. RESULTS: Of all patients, 90% had been treated with VKAs at some time since AF-diagnosis, 88% were still on treatment. 10% of the patients received aspirin as their anticoagulation therapy. INR was measured at least once a month in over 70% of the patients. INR values were 56% of the time within, 14% below and 30% over the target range. SF-36 results were similar to patients of comparable age and health. Fifty-five percent of patients reported they were always or mostly satisfied with their treatment and 66% stated they complied with their prescribed treatment most or all of the time. CONCLUSIONS: This study presents German "real-life" data in treating patients with AF and identifies the potential to advance the quality of care particularly with respect to anticoagulation.

Lung Cancer: Targets and Therapy, 2012

An economic evaluation was conducted in conjunction with a prospective, multicenter, randomized t... more An economic evaluation was conducted in conjunction with a prospective, multicenter, randomized trial, to compare pemetrexed with erlotinib in pretreated patients with metastatic non-small cell lung cancer (NSCLC) in Greece. Methods: The effectiveness of treatments examined was comparable; thus, cost minimization analysis was conducted to evaluate which option is less costly. Patient-level resource utilization data were combined with unit cost data, which were aggregated to compute the total treatment cost for each patient. The analysis was conducted with respect to the individual incurring the cost. Due to the limited life-expectancy of the patients, discounting was unnecessary. Since data were right censored, the Bang and Tsiatis method was employed to identify unbiased estimators of the mean cost per treatment arm, while other methods were employed for sensitivity analysis. To analyze uncertainty and to construct uncertainty intervals (UI), stochastic analysis was performed based on 5000 bootstrap replications. Results: The one-year survival rate was 28.3% in the pemetrexed arm and 31.7% in the erlotinib arm, while the corresponding median survival over the follow-up period was 7.1 and 6.7 months, respectively (P = 0.765). Total cost in the pemetrexed arm was €10508 (95% UI: €9552-€11488), while in the erlotinib arm the cost was €9563 (95% UI: €8499-€10711); thus, no statistically significant difference was found between the comparators (P = 0.206). Results remained constant for all sensitivity analyses. Conclusions: There is no survival or cost difference between erlotinib and pemetrexed; thus, these therapies are equivalent. Further studies are needed to determine whether other parameters, such as quality of life, differ among treatment options.

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

Current Medical Research and Opinion, 2006

The objective of the study was to assess the cost-effectiveness of two therapeutic alternatives f... more 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. 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. 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 euro2504 (euro2122 to euro2965) in the tiotropium arm and euro2655 (euro2111 to euro3324) in the salmeterol arm, a difference of -euro151 (-euro926 to euro580). 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 euro0 and reached 77% at a ceiling ratio of euro1000. Results stay fairly constant in various sensitivity analyses. 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.

Cost-Minimization Analysis of the Treatment of Patients With Metastatic Colorectal Cancer in Greece

Clinical Therapeutics, 2012

In 2008, colorectal cancer was the fourth most common cause of cancer-related death worldwide. Mo... more In 2008, colorectal cancer was the fourth most common cause of cancer-related death worldwide. Monotherapy with monoclonal antibodies directed against the epidermal growth factor receptor, such as cetuximab and panitumumab, has recently been introduced in the management of metastatic colorectal cancer (mCRC) patients. The aim of this study was to conduct a cost-minimization analysis comparing panitumumab with cetuximab in the treatment of patients with epidermal growth factor receptor-expressing mCRC with nonmutated (wild-type) Kirsten rat sarcoma viral oncogene homolog in Greece. The perspective of analysis was that of payers (Social Security Sickness Fund) and the country's National Health Service (NHS). The model was designed to contain probabilistic parameters to account for uncertainty and variation in these parameters. All resources consumed in local hospitals in the management of patients in each case were evaluated. Two analyses were performed: 1 evaluating cost per milligram and another evaluating cost per vial. From a payer perspective, the mean 20-week total cost per patient for panitumumab and cetuximab was: (1) per-milligram analysis: €16,349 and €18,242, respectively; and (2) per-vial analysis: €18,808 and €19,701. From the NHS perspective, the mean total costs per patient were slightly higher; however, the use of panitumumab was associated with a 17.7% and 12.4% cost reduction in per-milligram and per-vial analysis, respectively. The results of probabilistic models confirmed those of the deterministic analyses. In the Greek NHS and Social Security Sickness Fund setting, panitumumab monotherapy potentially constitutes a cost-saving option (versus cetuximab monotherapy) in the management of patients with mCRC and no mutation of Kirsten rat sarcoma viral oncogene homolog.

Cancer Management and Research, 2013

Background: Multiple myeloma is a hematologic malignancy that incurs a substantial economic burde... more Background: Multiple myeloma is a hematologic malignancy that incurs a substantial economic burden in care management. Since most patients with multiple myeloma eventually relapse or become refractory to current therapies (rrMM), the aim of this study was to assess the costeffectiveness of the combination of lenalidomide-dexamethasone, relative to bortezomib alone, in patients suffering from rrMM in Greece. Methods: An international discrete event simulation model was locally adapted to estimate differences in overall survival and treatment costs associated with the two alternative treatment options. The efficacy data utilized came from three international trials (MM-009, MM-010, APEX). Quality of life data were extracted from the published literature. Data on resource use and prices came from relevant local sources and referred to 2012. The perspective of the analysis was that of public providers. Total costs for monitoring and administration of therapy to patients, management of adverse events, and cost of medication were captured. A 3.5% discount rate was used for costs and health outcomes. A Monte Carlo simulation was used to estimate probabilistic results with 95% uncertainty intervals (UI) and a cost-effectiveness acceptability curve. Results: The mean number of quality-adjusted life years (QALYs) was 3.01 (95% UI 2.81-3.20) and 2.22 (95% UI 2.02-2.41) for lenalidomide-dexamethasone and bortezomib, respectively, giving an incremental gain of 0.79 (95% UI 0.49-1.06) QALYs in favor of lenalidomide-dexamethasone. The mean cost of therapy per patient was estimated at €77,670 (95% UI €76,509-€78,900) and €48,928 (95% UI €48,300-€49,556) for lenalidomidedexamethasone and bortezomib, respectively. The incremental cost per life year gained with lenalidomide-dexamethasone was estimated at €29,415 (95% UI €23,484-€37,583) and the incremental cost per QALY gained at €38,268 (95% UI €27,001-€58,065). The probability of lenalidomide-dexamethasone being a cost-effective therapy option at a threshold three times the per capita income (€60,000 per QALY) was higher than 95%. The results remained constant, without altering the conclusions, under several hypothetical scenarios. Conclusion: The combination of lenalidomide and dexamethasone may represent a costeffective choice relative to bortezomib monotherapy for patients in Greece with previously treated multiple myeloma.

Clopidogrel versus Aspirin in Patients with Atherothrombosis

Applied Health Economics and Health Policy, 2012

Atherothrombosis represents a leading cause of morbidity and mortality worldwide. Given the promi... more 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. 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. 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. 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, 12 921) for each QALY saved. 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.

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

Applied Health Economics and Health Policy, 2012

Current guidelines recommend treatment with antiplatelet and anticoagulant therapy for the second... more 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. 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. 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. 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 € 19 191, for the aspirin and aspirin plus clopidogrel treatment arms, respectively. The incremental cost-effectiveness ratio (ICER) with the addition of clopidogrel was &U20AC;2951 for each LY saved and &U20AC;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 &U20AC;7000 per discounted QALY gained. 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.

ClinicoEconomics and Outcomes Research, 2013

To quantify the economic effects of a child conceived by in vitro fertilization (IVF) in terms of... more To quantify the economic effects of a child conceived by in vitro fertilization (IVF) in terms of net tax revenue from the state's perspective in Greece. Methods: Based on previous international experience, a mathematical model was developed to assess the lifetime productivity of a single individual and his/her lifetime transactions with governmental agencies. The model distinguished among three periods in the economic life cycle of an individual: (1) early life, when the government primarily contributes resources through child tax credits, health care, and educational expenses; (2) employment, when individuals begin returning resources through taxes; and (3) retirement, when the government expends additional resources on pensions and health care. The cost of a live birth with IVF was based on the modification of a previously published model developed by the authors. All outcomes were discounted at a 3% discount rate. The data inputs-namely, the economic or demographic variables-were derived from the National Statistical Secretariat of Greece and other relevant sources. To deal with uncertainty, bias-corrected uncertainty intervals (UIs) were calculated based on 5000 Monte Carlo simulations. In addition, to examine the robustness of our results, other one-way sensitivity analyses were also employed. Results: The cost of IVF per birth was estimated at €17,015 (95% UI: €13,932-€20,200). The average projected income generated by an individual throughout his/her productive life was €258,070 (95% UI: €185,376-€339,831). In addition, his/her life tax contribution was estimated at €133,947 (95% UI: €100,126-€177,375), while the discounted governmental expenses for elderly and underage individuals were €67,624 (95% UI: €55,211-€83,930). Hence, the net present value of IVF was €60,435 (95% UI: €33,651-€94,330), representing a 182% net return on investment. Results remained constant under various assumptions for the main model parameters. Conclusion: State-funded IVF may represent good value for money in the Greek setting, since it has positive tax benefits for the government, notwithstanding its beneficial psychological effect on infertile couples.

ClinicoEconomics and Outcomes Research, 2015

We aimed to estimate the total mean annual treatment cost of different therapy options for patien... more We aimed to estimate the total mean annual treatment cost of different therapy options for patients with moderate-to-severe rheumatoid arthritis (RA) in Greece. Methods: A cost-minimization approach was adopted. An economic model was developed to estimate the direct costs of the three widely used treatments within a 1-year time horizon, from a health care payer perspective, either for new or for existing patients. Data on resource use, dose escalation, and frequency of therapy were based on a nationwide field survey of rheumatologists. Other analyses were also undertaken based on evidence from the literature. Total cost comprised the cost of drugs, administration, and hospital day care visits. Unit cost data were obtained from the price bulletin and the government gazettes issued by the Ministry of Health. Due to the short time horizon of the study, the cost was not discounted. Results: The mean annual total cost per new (or per existing) responder patient on etanercept was estimated at €9,845 (€9,840), and the total cost on etanercept/methotrexate (MTX) was estimated at €9,857 (€9,852). Therapy with etanercept had lower annual cost relative to adalimumab and infliximab. On an annual basis, it was estimated that the difference between etanercept monotherapy and adalimumab monotherapy was €544 (€1,323). Similarly, the difference between etanercept/MTX and infliximab/MTX was €1,871 (€1,490) and €543 (€1,323), respectively, relative to adalimumab/MTX. Results remained constant under other scenario analyses undertaken. Conclusion: In the real-life practice setting in Greece, where dose intensity and frequency differences occur, etanercept alone or in combination with MTX, if prescribed as per label, represents the option with lower annual cost per patient when compared with adalimumab or infliximab in patients with RA. These results hold true as long as the assumptions and data used in the analysis remain stable and may alter if any of the underlying parameters, such as drug price, change.

ClinicoEconomics and Outcomes Research, 2012

Background: The purpose of this study was to compare Gonal-F ® , a recombinant follicle-stimulati... more Background: The purpose of this study was to compare Gonal-F ® , a recombinant follicle-stimulating hormone, with Menopur ® , a highly purified human menopausal gonadotrophin (hpHMG) in assisted reproduction in Greece. Methods: A decision tree in combination with a Markov model was used to assess the clinical and economical impact of comparators for up to three consecutive cycles. Transition probabilities were derived from the literature and validated by clinical experts. Cost components were derived from the electronic databases of selected private and public clinics. A probabilistic sensitivity analysis was performed to deal with uncertainty and to construct a cost-effectiveness acceptability curve. Results: There was a statistically significant difference in favor of the recombinant folliclestimulating hormone arm compared with hpHMG, which was associated with 52 more births (95% uncertainty interval 26-78, P = 0.001) per 1000 patients. The cost per birth was estimated at €16,906 and €17,286 in the recombinant follicle-stimulating hormone and hpHMG arms, respectively. The cost per in vitro fertilization was estimated at €4365 in the recombinant folliclestimulating hormone arm and €3815 in the hpHMG arm, indicating a difference of €550. The incremental cost per birth for recombinant follicle-stimulating hormone versus hpHMG was estimated at €14,540, while the incremental cost per life-year was estimated at €175.41. Conclusion: Recombinant follicle-stimulating hormone may represent a cost-effective choice compared with hpHMG when used for ovarian stimulation for a pharmacoeconomic point of view in the Greek public health care setting. However, it must be noted that in clinical practice both agents may be used together to increase the number of follicles, oocytes, embryos, and/or pregnancies in treated patients, an approach which has not been evaluated in Greece or reported in the literature due to obvious limitations.