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

OBJECTIVE: To conduct an economic evaluation estimating the cost per live birth after controlled ovarian stimulation (COS) using Follitropin Alpha (Gonal-F), in the Greek National Health System setting. A secondary objective was to predict the live birth rateof the In Vitro Fertilization (IVF) procedure. METHODS: A single arm, multi-center, prospective, non-interventional study was conducted on which economic, efficacy and safety data were collected by six of the largest IVF centers. The participants were 350 female patients. Three statistical methods were employed for the analysis of the study outcomes, namely (a) Generalized Linear Modeling for the estimation of the costs of IVF treatment, (b) multivariable logistic regression and (c) an Artificial Neural Network (ANN) model for live birth prediction. RESULTS: The mean total cost of IVF therapy per patient was estimated at €3728 (95% CI: €3679-€3780), while the total cost per live birth was €14,872 (95% CI: €12,441-€17,951). The live birth rate after 3 complete IVF cycles was estimated at 22.9%, while the percentage of those suffering from OHSS was limited at 0.57%. In logistic regression, the Ovarian Sensitivity Index (OSI) was a factor found to be positively associated with live birth (OR 7.39, 95% CI: 1.84-29.71). For the ANN, important predictors included number of gestational sacs and the duration of infertility. CONCLUSION: The present study constitutes the largest single-arm study based on real data in Greece to date. The cost of IVF treatment and the cost per live birth are not insignificant in this NHS setting. The live birth rate, cost per oocyte, and the cost per live birth are in line with literature. OSI was a main contributing factor to the accurate prediction of the live birth rate, while age and BMI were found to be negatively correlated.

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

BACKGROUND AND OBJECTIVE: Subfertility 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. METHODS: A 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. RESULTS: The 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. CONCLUSION: The 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.

Annual biologic treatment cost for new and existing patients with moderate to severe plaque psoriasis in Greece.

AIM: The aim of the present study was to estimate the annual per-patient cost of treatment with adalimumab, etanercept, infliximab, and ustekinumab by response status for new and existing patients with moderate to severe psoriasis in Greece. METHODS: An economic analysis was developed from a national health care perspective to estimate the direct cost of treatment alternatives for new and existing patients within a 1-year time horizon. The model included drug acquisition and administration costs for responders and nonresponders. Real-world treatment pattern and resource use data were extracted through nationwide field research using telephone-based interviews with a representative sample of dermatologists. Unit costs were collected from official sources in the public domain. RESULTS: The mean annual cost of treatment for new patients who responded (or did not respond) to treatment was as follows: adalimumab €10,686 (€3,821), etanercept €10,415 (€3,224), infliximab €14,738 (€7,582), and ustekinumab €17,155 (€9,806). For existing patients the mean annual cost was €9,916, €9,462, €12,949, and €17,149, respectively. Results did not change significantly under several one-way sensitivity and scenario analyses. CONCLUSION: Under the base-case scenario, the cost of treatment with etanercept is lower than that of the other biological agents licensed for moderate to severe plaque psoriasis in Greece, for both new and existing patients, irrespective of response status.

The cost of blood collection in Greece: an economic analysis.

OBJECTIVE: 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. METHODS: 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 economic data collected by the National School of Public Health and the Ministry of Health. All data refer to the year 2013. RESULTS: The weighted mean direct cost of producing 1 unit of blood was estimated at €131.49 (SD, €22.12; minimum/maximum, €94.96-€239.20). The mean total indirect cost was estimated at €34 per unit of blood. The cost distribution was positively skewed (skewness, 1.642 [0.327]). The major cost component was the cost of personnel, accounting for 32.5% of total costs, and the average of blood unit wastage was estimated at 4.90%. There were no differences between the cost of producing 1 unit of blood in Athens compared with the rest of the country (Mann-Whitney test, P = 0.341). CONCLUSIONS: This study suggests that the cost of producing 1 unit of blood is not insignificant. These figures need to be complemented with those concerning the cost of transfusion to have a complete picture of producing and using 1 unit of blood locally.

The efficiency of the public dental services (PDS) in Cyprus and selected determinants.

BACKGROUND: Currently there is a dual system of oral healthcare delivery in Cyprus: the public dental system (PDS) run by the Government and the private system provided by private dental practitioners. Although 83% of the population is entitled to free treatment by the PDS only 10% of the population make use of them. As Cyprus faces now the challenges of the introduction of a new health care system and rising healthcare costs in general, surveys that examine, among other things, the efficiency of the PDS become very important as tools to make important cost savings. The aims of this study are to assess trends regarding the number of visits and the age distribution of patients using PDS from 2004 to 2007, to measure the technical efficiency of the PDS and to investigate various factors that may affect it. METHODS: Non-parametric Data Envelopment Analysis (DEA) was employed to assess technical efficiency. Two separate cases were examined. Efficiency was calculated, firstly using as inputs the wages and the working hours of the personnel, and secondly the working hours of the personnel and the cost of the materials. As outputs, in both cases, the treatment offered (divided into primary, secondary and tertiary care) and the numbers of visits were used. In the second stage Tobit analysis was used to explore various predictors of efficiency (time per patient, location, age of dentists, age of patients and age of assistants). RESULTS: The study showed that whilst there was an increase in the number of patients using the PDS from 2004 to 2007, only a small proportion of the population (10%) make use of them. Women, middle and older aged patients, make more use of the PDS. Regarding efficiency, there were large differences between the units. The average Technical Efficiency score was 68% in the first model and 81% in the second. Urban areas and low time per patient are predictors of increased efficiency. CONCLUSION: The results suggest that many of the rural PDS are underperforming. Given that the option of shutting them down is undesirable, measures should be taken to reduce inputs (e.g. by reducing the personnel's working hours) and to increase outputs (remove barriers, make PDS more accessible and increase the number of patients).

Estimating the long-term effects of in vitro fertilization in Greece: an analysis based on a lifetime-investment model.

OBJECTIVE: 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.

Cost-minimization analysis of the treatment of patients with metastatic colorectal cancer in Greece.

BACKGROUND: 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. OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Economic evaluation of alternative assisted reproduction techniques in management of infertility in Greece.

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 follicle-stimulating 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 follicle-stimulating 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.

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

BACKGROUND: 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. 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. 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. 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. 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.

Economic evaluation of statins in high-risk patients treated for primary and secondary prevention of cardiovascular disease in Greece.

BACKGROUND: An economic evaluation was undertaken in order to assess several therapeutic alternatives (rosuvastatin, atorvastatin, simvastatin, and pravastatin) for the prevention of primary and secondary cardiovascular events in high-risk patients in Greece. METHODS: A probabilistic Markov model with five distinct states provided estimates over a 20-year time span. The relative effectiveness of comparators was based on the literature. The HellenicSCORE risk equation was used to forecast survival. The transition probabilities from acute myocardial infarction or stroke to death were estimated with reference to the Framingham study. In addition, Framingham scores were used to calculate the probability of nonfatal acute myocardial infarction or nonfatal stroke. Costs were estimated from the perspective of sickness funds and included direct medical costs valued in the year 2012. The total treatment cost accounted for the cost of drugs, routine examinations, and resources expended in the management of acute myocardial infarction, stroke, and death. The utility decrements used are those for the Greek population. A supplementary budget impact analysis was also conducted. RESULTS: The mean discounted quality-adjusted life years in the case of males for the rosuvastatin arm were 10.18 versus 10.04, 9.94, and 9.88 for atorvastatin, simvastatin, and pravastatin, respectively. The mean total cost was €15,392, €16,438, €17,009, and €17,356 for rosuvastatin, atorvastatin, simvastatin, and pravastatin, respectively. Similar results were obtained in the case of females, while all analyses demonstrated a statistically significant difference at the 95% level of significance. The total burden of 100% (single) use of rosuvastatin in a hypothetical cohort of 100 male patients for one year was €1.47 million versus €1.53 million for atorvastatin, €1.57 million for simvastatin, and €1.59 million for pravastatin. CONCLUSION: Rosuvastatin may represent an attractive choice compared with likely alternative existing therapies used in the primary and secondary prevention of cardiovascular events by the National Health Service of Greece.

Economic evaluation of clopidogrel in acute coronary syndrome patients without ST-segment elevation in Greece: a cost-utility analysis.

BACKGROUND: 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. 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. 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. 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 € 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. 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 intravenous iron treatments in the management of anemia patients in Greece.

PURPOSE: To conduct an economic evaluation comparing Ferinject(®) (ferric carboxymaltose [FCM]) with Venofer(®) (iron sucrose [IS]) and CosmoFer(®) (low-molecular-weight iron dextran [LMWID]) in the management of iron deficiency anemia in Greece. PATIENTS AND METHODS: A cost-minimization analysis was conducted since there are no clear data indicating that one of these regimens is superior to the others in terms of efficacy. Main data inputs were based on bibliography and validated by clinicians. The economic evaluation was conducted for inpatients (ie, surgical patients or patients hospitalized due to a disease related to chronic or acute blood loss) and outpatients (eg, nondialysis chronic kidney disease patients), separately. Analysis was carried out from a National Health Service (NHS) perspective and also from a patient perspective. Total cost treatment reflects the cost of drugs, the cost of all resources expended in patient management such as the cost of disposables for each infusion, the monitoring costs during infusion (salaries of personnel), other hospital expenses, the cost for management of adverse events, the productivity loss, and the traveling cost for patients. RESULTS: In the case of outpatients, the mean total cost per patient in the FCM arm was €198.6, in the IS arm €627.7, and in the LMWID arm, €510.5. For inpatients the mean total cost was estimated at €189.2 for FCM while it was €419.9 and €228.8 for IS and LMWID, respectively. Budget impact analysis for a typical Greek hospital with 100 patients revealed that the total cost of FCM (inpatients analysis) was 113% and 15.4% lower against their comparators. In an outpatient situation, the total cost of FCM was 201.1% and 151.8% lower compared with IS and LMWID, respectively. CONCLUSION: Ferric carboxymaltose may represent a cost-saving option compared with the most likely alternative existing therapies used for the management of anemia in the National Health Service of Greece.

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

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 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. 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.