Comparative Analysis of Legislative Requirements About Patients' Access to Biotechnological Drugs for Rare Diseases in Central and Eastern European Countries.

Objectives: The aim of the study was to compare the access of patients with rare diseases (RDs) to biotechnological drugs in several Central and Eastern European countries (CEECs). We focused on the legislative pricing and reimbursement requirements, availability of biotechnological orphan medicinal products (BOMPs) for RDs, and reimbursement expenditures. Methods: A questionnaire-based survey was conducted among experts from 10 CEECs: Bulgaria, Croatia, Estonia, Greece, Hungary, Poland, Romania, Slovakia, Serbia, and Macedonia. The legal requirements for reimbursement and pricing of BOMPs were collected. All BOMPs and medicines without prior orphan designations were extracted from the European list of orphan medicinal products, 2017. The reimbursement status of these medicinal products in 2017 in the public coverage of the included CEECs as well as the share of their costs in relation to the total public pharmaceutical spending for the period from 2014 to 2016 were defined. Results: Our survey revealed that some differences in the legal requirements for pricing and reimbursement of BOMPs amongst the countries included in the study. All European Union countries have developed and implemented pharmacoeconomic guidelines with or without some specific reimbursement requirements for orphan medicinal products. Cost-effectiveness analysis, cost-utility analysis, Markov models, meta-analysis, and discount levels of costs and results were required only in Bulgaria, Poland and Hungary. The number of reimbursed BOMPs and biotechnological medicinal products for RDs without prior orphan designation was the highest in Hungary (17 and 40, respectively). Patient-based reimbursement schemes were available only in Hungary for 11 out of 17 BOMPs. Poland and Greece have the highest pharmaceutical expenditure of reimbursed BOMPs with are ~214 million and 180 million EUR, respectively in the observed period from 2014 to 2016. High proportion of the pharmaceutical expenditure on the reimbursed biotechnological medicinal products for RDs for the observed period 2014-2016 is presented in Bulgaria and Slovakia. Conclusions: The non-European Union CEECs face a significant delay in the legal implementation of pharmacoeconomic guideline for assessment of BOMPs. The access to BOMPs is similar among the observed CEECs and the countries with the best access are Hungary and Greece. The influence of BOMP expenditures on the budget in the individual countries is significant.

Cost effectiveness of vildagliptin versus glimepiride as add-on treatment to metformin for the treatment of diabetes mellitus type 2 patients in Greece.

OBJECTIVES: This study was designed to assess the cost-effectiveness of vildagliptin versus glimepiride as add-on to metformin in the management of type 2 diabetes mellitus (T2DM) patients in the Greek healthcare setting. METHODS: A cost-effectiveness model was designed, using MS Excel, to compare two treatment strategies. Strategy 1 consisted of first-line metformin, followed by metformin + vildagliptin in second-line, while strategy 2 consisted of first line metformin, followed by metformin + glimepiride in second line. Subsequent lines were the same in both strategies and consisted of metformin + basal insulin and metformin + basal + rapid insulin. Clinical data and utility decrements relating to diabetes complications were taken from the published literature. Only direct medical costs were included in the analysis (cost base year 2014), and consisted of drug, adverse events and comorbidity costs (taken from local officially published sources and the literature). The perspective adopted was that of the Social Insurance Fund. The time horizon was lifetime, and future costs and outcomes were discounted at 3.5% per annum. RESULTS: Adding vildagliptin to metformin increased drug costs compared with adding glimepiride to metformin (€2853 vs. €2427, respectively). However, this increase was offset by a decrease in the costs of associated comorbidities (€4393 vs. €4539) and adverse events (€2757 vs. €3111), resulting in a lower total cost of €74 in strategy 1 compared with strategy 2. Comorbidities were the largest cost component in both strategies, accounting for 43.9 and 45.0% in strategies 1 and 2, respectively. Strategy 1 was also associated with increased life-years (LYs, 0.11) and quality-adjusted life-years (QALYs, 0.11) compared with strategy 2. Strategy 1 is therefore dominant, as it is associated with both lower overall costs and increased effectiveness. CONCLUSIONS: Vildagliptin as add-on treatment to metformin in the management of T2DM in Greece appears to be dominant versus. glimepiride in terms of both cost per LY and cost per QALY gained.

Treatment Compliance with Fixed-Dose Combination of Vildagliptin/Metformin in Patients with Type 2 Diabetes Mellitus Inadequately Controlled with Metformin Monotherapy: A 24-Week Observational Study.

Objective. To evaluate the differences in treatment compliance with vildagliptin/metformin fixed-dose versus free-dose combination therapy in patients with type 2 diabetes mellitus (T2DM) in Greece. Design. Adult patients with T2DM, inadequately controlled with metformin monotherapy, (850 mg bid), participated in this 24-week, multicenter, observational study. Patients were enrolled in two cohorts: vildagliptin/metformin fixed-dose combination (group A) and vildagliptin metformin free-dose combination (group B). Results. 659 patients were enrolled, 360 were male, with mean BMI 30.1, mean T2DM duration 59.6 months, and mean HbA1c at baseline 8%; 366 patients were assigned to group A and 293 to group B; data for 3 patients was missing. In group A, 98.9% of patients were compliant with their treatment compared to 84.6% of group B. The odds ratio for compliance in group A versus B was (OR) 18.9 (95% CI: 6.2, 57.7; P < 0.001). In group A mean HbA1c decreased from 8.1% at baseline to 6.9% (P < 0.001) at the study end and from 7.9% to 6.8% (P < 0.001) in group B. Conclusions. Patients in group A were more compliant than patients in group B. These results are in accordance with international literature suggesting that fixed-dose combination therapies lead to increased compliance to treatment.

The Cost of Managing Type 2 Diabetes Mellitus in Greece: A Retrospective Analysis of 10-Year Patient Level Data "The HERCULES Study".

Objective. This study aimed to estimate the mean annual cost of treating type 2 diabetes mellitus patients (T2DM) including complications and comorbidities in Greece. Design. A noninterventional retrospective study was based on patient level data analysis (bottom-up approach) from medical records, with at least 10-year-follow-up data. Results. The total annual cost per patient for managing diabetes in Greece was estimated at € 7,111 and was, statistically significantly, higher for patients with inadequate glycemic control (Hba1c > 7%) versus patients with adequate control (Hba1c = 7%) (€ 7,783 versus € 6,366, resp.; P = 0.017). This was mainly attributed to difference in CV hospitalizations between groups 14/111 versus 4/100, respectively, OR = 3.46 (95% CI: 1.10-10.9) for inadequately controlled patients. The largest component of cost was management of comorbidities, accounting for 48% of costs, and pharmaceutical treatment at 35.9% while only 14.9% was attributed to diabetes treatment per se. Obese men and patients with poor education are the groups with higher treatment costs. Conclusions. This is the first study to capture all cost components and the real burden of diabetes in Greece. Comorbidities were found to account for almost half of total cost, significantly higher in nonoptimally controlled diabetes patients.

Budget impact analysis on erythropoiesis-stimulating agents use for the management of chemotherapy-induced anaemia in Greece.

BACKGROUND: Chemotherapy-induced anaemia is a common and significant complication of chemotherapy treatment. Blood transfusion and administration of Erythropoiesis-Stimulating Agents (ESAs) either alone or in combination with iron are the most widely used therapeutic options. In Greece, ESAs are among the top ten therapeutic groups with the highest pharmaceutical expenditure, since they are fully reimbursed by social security funds. The objective of the study is to determine potential cost savings related with the use of biosimilar over originator ESAs for the management of the newly diagnosed chemotherapy-induced anemic patients. METHODS: A budget impact analysis has been carried through the elaboration of national epidemiological, clinical and economic data. Epidemiological data derived from WHO (GLOBOCAN) and the European Cancer Anaemia Survey. Clinical data reflect oncology patients' disease management. ESAs consumption was based on data from the biggest social security fund (IKA). The administration of ESAs under different dosing schemes and time periods has been estimated by separating them in originators and biosimilars as well as by classifying anaemic patients in responders and non-responders. Cost analysis is based on newly diagnosed patients' alternative treatment scenarios. Treatment costs and prices are used in 2012 values. The Social Security Funds's perspective was undertaken. RESULTS: Based on the annual incidence rates, 2.551 newly diagnosed chemotherapy-induced anemic patients are expected to be treated with ESAs. Average cost of treatment on originators ESAs for responders is €2.887 for the 15-week ESAs treatment and €5.019 for non-responders, while on biosimilars €2.623 and €4.009 respectively. Treatment cost on biosimilars is 10.1% lower than originators for responders and 25.2% for non-responders. Budget impact estimates show that treating anemic patients with originator ESAs was estimated at €10.084.800 compared to €8.460.119 when biosimilar ESAs were used, leading to an overall 19,20% cost reduction favoring biosimilars. CONCLUSION: In Greece, the treatment on biosimilar ESAs seems to be a cost saving option over originators for the newly diagnosed chemotherapy-induced anemic patients, since it corresponds to 5% of the annual overall consumption and expands patients' access to ESAs treatment. Health care decision making should rely on evidence based treatments in order to achieve social funds' sustainability in an era of economic recession.

The prevalence of hypoglycemia and its impact on the quality of life (QoL) of type 2 diabetes mellitus patients (The HYPO Study).

OBJECTIVE: To estimate the impact of hypoglycemia on the Quality of Life (QoL) and its prevalence in patients with type 2 diabetes mellitus (T2DM) in Greece. DESIGN: A cross-sectional epidemiological study was conducted in 6631 patients with T2DM. QoL was assessed with the patient self-administered ADDQoL-19. Reliability analysis of patients' outcomes was performed to assess internal consistency of the ADDQoL-19. Patients were categorized according to hypoglycemia experience and diabetes control. Controlled patients were considered as having Hb1Ac <7% (53 mmol/mol) and hypoglycemic episodes were defined as laboratory-confirmed clinical symptomatic events. RESULTS: In total, 59% of the sample had HbA1c >7% (53 mmol/mol) and 20.4% of patients had a history of laboratory-confirmed hypoglycemia. The mean age was 60 years and the mean T2DM duration was 10 years. The mean QoL score was -3.09±1.9 for the total sample and the mean score of non-hypoglycemic patients was -3.05±2, while the respective score of hypoglycemic patients was -3.26 ±1.8, (p≤0.001). Similar results were observed in the group of controlled and uncontrolled patients, who scored -2.73±1.7 and -3.33±1.9, respectively (p≤0.001). Comparable results were identified in the majority of the ADDQoL-19 instrument dimensions. CONCLUSIONS: The QoL of T2DM patients is affected significantly by hypoglycemia and the level of disease control. In diabetes treatment, the ultimate goal should be optimal glycemic control without debilitating hypoglycemic episodes which compromise patients' QoL.

The cost of COPD exacerbations: a university hospital--based study in Greece.

BACKGROUND: Hospitalization attributed to severe exacerbations is the major cost driver of Chronic Obstructive Pulmonary Disease (COPD). Given that in Greece no previous studies have addressed the economic burden of COPD, the aim of the study was to examine the hospitalization cost of COPD patients with severe exacerbations in the region of Thrace. METHODS: Sample consisted of 142 COPD patients with severe exacerbations who were admitted to the pneumonology department of the University Teaching Hospital of Alexandroupolis (UTHA) in 2006 and 2007. Data collection was performed retrospectively and resource utilization was derived from patients' files. General Linear Model univariate analysis was applied in order to test the influence of disease severity on costs. RESULTS: Mean actual cost per severe exacerbation was €1711; the amount of €621 is reimbursed by social security funds. Price discrepancies are observed between the actual and the nominal cost per patient in all disease stage categories. Mean hospitalization cost per COPD patient increases slightly with the severity of the disease. However, in the very severe stage it greatly increases mainly due to Intensive Care Unit (ICU) admission. In multivariate analysis the length of stay and the stage of the disease were both related to significantly increased costs, while the existence of co-morbidities exhibited marginal significant relation to increased cost. CONCLUSIONS: The cost estimation of severe exacerbations is important as it could trigger further research and also provide the opportunity of creating national epidemiological and economic data. Such data could contribute to the estimation of the total economic and societal burden of COPD in the country.

The economic burden of treating neonates in Intensive Care Units (ICUs) in Greece.

BACKGROUND: In a period when a public-private mix in Greece is under consideration and hospital budgets become restrained, economic assessment is important for rational decision making. The study aimed to estimate the hospitalization cost of neonates admitted to the ICUs and demonstrate discrepancies with reimbursement. METHODS: Chosen methodology was based on the selection of medical records of all NICUs and intermediate care admissions within February to April 2004. Neonates (n = 99) were classified according to birthweight and gestational age. RESULTS: Mean cost per infant was estimated at euro5.485 while reimbursement from social funds arises to euro3.952. Costs per birthweight or gestational age show an inverse relationship. Personnel costs accounted for 59.9%, followed by enteral/parenteral feeding (16.14%) and pharmaceuticals expenses (11.10%) of all resources consumed. Sensitivity analysis increases the robustness of the results CONCLUSION: Neonatal intensive care in Greece is associated with significant costs that exceed reimbursement from social funds. Reimbursement should be adjusted to make neonatal intensive care economically viable to private hospitals and thus, increase capacity of the services provided.

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.