Incidence and cost of bleeding events requiring hospitalization in patients with atrial fibrillation treated with acenocoumarol in Greece.

BACKGROUND: To estimate the incidence of hemorrhagic events in patients with atrial fibrillation (AF) treated with acenocoumarol, and the management cost of those requiring hospitalization in Greece. METHODS: A nationwide telephone survey was conducted between December 2017 and January 2018, to identify cardiologists who treat AF patients with acenocoumarol. A total of 300 cardiologists were selected and reported the number of AF acenocoumarol-treated patients during the past 12 months and the number of those who experienced a hemorrhagic event. The hospital charges to sickness fund and the cost of resource utilization of AF patients hospitalized between January 2013 and June 2017 at a tertiary hospital in Athens due to acenocoumarol-related bleedings were retrieved. RESULTS: Out of 48,255 AF patients, 12,633 (26.2%) were treated with acenocoumarol. In all, 5.1% of patients experienced a hemorrhagic event with the incidence of bleeding requiring hospitalization being 1.7%. The most common bleeding site was the gastrointestinal system (51.5%). The mean (95% CI) management cost per bleeding event requiring hospitalization was €1,202 (€1,058-€1,420). The higher cost was that of intracranial bleeding €3,887 (€2,700-€5,046). The expected annual economic burden for the management of bleedings related to acenocoumarol and requiring hospitalization was estimated at €1,463,955. CONCLUSIONS: The incidence of bleeding events in AF acenocoumarol-treated patients in Greece as well as the estimated annual economic burden for the management of bleeding events requiring hospitalization, emphasize the need to comply with the current guidelines and to optimize therapeutic strategies for the management of AF side effects with oral anticoagulants, particularly in patients with high bleeding risk.

The Economic Burden of Asthma in Greece: A Cross-Sectional Study.

BACKGROUND: The high prevalence rates of asthma worldwide and the chronic nature of the disease make asthma a major cause of morbidity, imposing a significant socio-economic burden in many countries. Specifically in Greece, the self-reported prevalence of asthma reached 9% in 2017. OBJECTIVES: The objective of this study was to estimate the total management cost of asthma in Greece and its potential determinants. METHODS: A population-based, random-digit-dialed telephone nationwide survey was conducted to recruit patients with asthma in Greece (n = 353). A structured questionnaire was used to collect data on demographic and lifestyle characteristics, exacerbations, asthma control, medical resource utilization, and productivity loss during the past 12 months. The total annual direct cost from the societal, payer, and patient perspective as well as the indirect cost was calculated. All costs refer to the year 2017 (€). The significance level was set to α = 0.05. RESULTS: The mean (95% confidence interval) annual total cost per patient for asthma management from the societal, payer, and patient perspective was €895 (696-1105), €673 (497-861), and €151 (119-188), respectively. The direct medical cost accounted for almost 90% of the total cost, whereas only 4% was attributed to the indirect cost. The direct medical cost was mainly driven by the medication cost (48%). The total annual societal cost was statistically significantly higher in those with not well-controlled asthma (p = 0.014) and those experiencing exacerbations during the past 12 months (p < 0.001) than in their counterparts. The total annual economic burden of asthma in Greece was estimated at €727 million and €547 million from the societal and payer perspective, respectively. CONCLUSION: Our findings indicate that asthma imposes a high economic burden on society and the healthcare system in Greece. Therefore, greater investment in interventions aimed at asthma control and prevention of acute exacerbations may reduce the overall burden of asthma in Greece.

The self-reported prevalence and disease burden of asthma in Greece.

OBJECTIVES: The primary objective was to estimate the self-reported prevalence of asthma in Greece. The secondary one was to assess the impact of asthma control on patients' health related Quality-of-Life (HRQoL), productivity loss, daily activities and psychological distress. METHODS: A population-based, random-digit dialing, telephone nationwide survey was conducted to recruit patients with asthma. Among the responders, 3,946 met the age criterion (≥18 years) and completed the screening questions regarding asthma. Of them, 353 subjects reported that they had been diagnosed with asthma sometime in their life and completed the survey. Data on demographic and lifestyle characteristics, asthma control, comorbidities, limitations in daily activities, psychological distress, productivity loss, as well as HRQoL, were collected through telephone interview. RESULTS: The lifetime self-reported prevalence of asthma was found to be 9.10% (95% CI:8.14%-9.94%). Sixty three percent of patients had well-controlled (WC) asthma. Asthma control was associated with gender, age, and specific comorbidities. Moreover, patients with not well-controlled (NWC) asthma were more likely to have missed work and reduced productivity during the past 12 months due to their asthma (p < 0.01). Patients with NWC asthma were more likely to declare psychological distress and limitations in their daily living activities. Patients' HRQoL with NWC asthma was significantly worse (0.65 ± 0.24) compared to those with WC asthma (0.86 ± 0.17, p ≤ 0.001). CONCLUSIONS: The results of this survey revealed the link between the asthma control and burden of disease demonstrating the need for the implementation of programs aiming at the management of chronic symptoms related to this condition.

The Economic Burden of Chronic Obstructive Pulmonary Disease in Greece.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of disability and death worldwide, imposing a substantial socioeconomic burden on societies and patients due to the long-term management required. OBJECTIVE: To assess the economic burden of COPD in Greece and its potential determinants. METHODS: A population-based, random-digit dialled, telephone nationwide survey was conducted to recruit patients with COPD in Greece (N = 351). A structured questionnaire was used to collect data. The total annual cost per patient from a societal perspective was calculated. RESULTS: The mean (95% CI) annual total cost per patient for the management of COPD from a societal perspective was €2150 (€1879-€2443). The total annual cost was mainly driven by the medication cost (36.1%), followed by the cost of hospitalizations (26.7%) and long-term oxygen therapy (13.8%). Multiple generalized linear model revealed that age, COPD Assessment Test (CAT) score and exacerbations were independently associated with the total annual cost. CONCLUSION: Investment in interventions aiming at delaying progression of disease, preventing acute exacerbations, and managing chronic symptoms are required to reduce the overall economic burden of COPD in Greece.

Economic evaluation of trifluridine and tipiracil hydrochloride in the treatment of metastatic colorectal cancer in Greece.

AIM: To evaluate the cost-effectiveness of trifluridine and tipiracil hydrochloride (FTD/TPI) compared with best supportive care (BSC) or regorafenib for the treatment of patients with metastatic colorectal cancer who have been previously treated with or are not considered candidates for available therapies including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-VEGF agents and anti-EGFR agents in Greece. METHODS: A partitioned survival model was locally adapted from a third-party payer perspective over a 10 year time horizon. Efficacy data and utility values were extracted from published studies. Resource consumption data were obtained from local experts using a questionnaire developed for the purpose of the study and was combined with unit costs obtained from official sources. All costs reflect the year 2017 in euros. Primary outcomes were patients' life years (LYs), quality-adjusted life years (QALYs), total costs and incremental cost-effectiveness ratios (ICERs) per QALY and LYs gained. RESULTS: Total life time cost per patient for FTD/TPI, BSC and regorafenib was estimated to be €10,087, €1,879 and €10,850, respectively. In terms of health outcomes, FTD/TPI was associated with 0.25 and 0.11 increment in LYs compared with BSC and regorafenib, respectively. Furthermore, FTD/TPI was associated with 0.17, and 0.07 increment in QALYs compared with BSC and regorafenib, resulting in ICERs of €32,759 per LY gained and €49,326 per QALY gained versus BSC. Moreover, FTD/TPI was a dominant alternative over regorafenib. CONCLUSION: The results indicate that FTD/TPI may represent a cost-effective treatment option compared with other alternative therapies as a third-line treatment of metastatic colorectal cancer in Greece.

Development of multi-criteria decision analysis (MCDA) framework for off-patent pharmaceuticals - an application on improving tender decision making in Indonesia.

BACKGROUND: Off-patent pharmaceuticals (OPPs) hold vital importance in meeting public health objectives, especially in developing countries where resources are limited. OPPs are comprised of off-patent originals, branded generics and unbranded generics; nonetheless, these products are not identical and often there are differences in their equivalence, manufacturing quality standards and reliability of supply. This necessitates reconsideration of the lowest price policy objective in pharmaceutical decision making. The aim of this study was to develop a Multi-Criteria Decision Analysis (MCDA) framework through a pilot workshop to inform the national procurement of OPPs in Indonesia. METHODS: An initial list of potentially relevant criteria was identified based on previous work and a literature review. In a 2-day pilot policy workshop, twenty local experts representing different stakeholder groups and decision-making bodies selected the final criteria, approved the scoring function for each criterion, and assigned weights to each criterion. RESULTS: An MCDA framework was proposed for OPP drug decision making in developing countries, which included price and 8 non-price criteria. Based on the pilot policy workshop 6 + 1 criteria were considered relevant for Indonesia: pharmaceutical price (40% weight), manufacturing quality (18.8%), equivalence with the reference product (12.2%), product stability and drug formulation (12.2%), reliability of drug supply (8.4%), real world clinical or economic outcomes, such as adherence or non-drug costs (4.2%) and pharmacovigilance (3.6%). CONCLUSIONS: According to the pilot policy workshop, other criteria apart from price need to be strengthened in the tendering process. The introduction of additional criteria for OPP procurement in an MCDA framework creates incentives for manufacturers to invest into improved manufacturing standards, equivalence proof, product quality, reliability of supply or even additional real-world data collection, which ultimately may result in more health gain for the society.

Treating EGFR-Mutated Oncogene-Addicted Advanced Non-Small-Cell Lung Cancer in the Era of Economic Crisis in Greece: Challenges and Opportunities.

PURPOSE: Because of the profound financial crisis that commenced in Greece in 2010, severe cuts in health care spending and other restriction measures led to significant delays in the reimbursement of novel antineoplastic agents. In 2011, the Hellenic Society of Medical Oncology initiated a program of early access to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors for the treatment of patients with advanced, EGFR-mutant non-small-cell lung cancer (NSCLC). We evaluated treatment patterns and clinical outcomes in patients with EGFR-mutant or wild-type disease treated at a large center in Greece throughout the period of financial crisis. PATIENTS AND METHODS: From 2011 through 2015, 252 patients with newly diagnosed advanced NSCLC were treated at the Department of Medical Oncology of the Papageorgiou Hospital, a tertiary cancer center in northern Greece. We retrospectively reviewed patient medical records to obtain clinicopathologic characteristics, EGFR mutation status, and follow-up data. The primary end point was time to treatment failure. RESULTS: Of the 198 evaluable patients, 25 (12%) had EGFR mutations. All patients with EGFR mutations except one received treatment with an EGFR tyrosine kinase inhibitor. Median times to treatment failure for patients with EGFR-mutant and wild-type disease were 15.8 and 7.1 months, respectively (hazard ratio, 0.58; 95% CI, 0.35 to 0.95; P = .031). There was no difference in overall survival between the two groups ( P = .293). No deviation from treatment guidelines or discontinuation of treatment regimens occurred because of logistic reasons or drug shortages. CONCLUSION: Despite restrictions in the reimbursement policy and accompanying controls in the use of high-cost medicines, the national program enabled treatment of patients with EGFR-mutant NSCLC according to established guidelines. Therefore, the clinical outcomes of such patients treated in Greece during the economic crisis were in accordance with international standards.

Guidance toward the implementation of multicriteria decision analysis framework in developing countries.

INTRODUCTION: Multiple Criteria Decision Analysis (MCDA) is increasingly used in health care mainly because it moves decision-making from ad hoc to an evidence-based and comprehensive process. Developing countries with more restricted financial and human research capacities, however, should consider their own methods of MCDA development and implementation. Areas covered: An MCDA framework to improve procurement decisions of off-patent pharmaceuticals was developed for developing countries and adapted to Indonesia, Kazakhstan and Vietnam during three policy workshops. Based on the experience of these workshops and one joint workshop with international experts and decision makers from multiple developing countries, general recommendations were formulated on how to implement MCDA specifically in developing countries. We provide 17 practical MCDA implementation recommendations in four major areas, including (1) MCDA objectives; (2) technical considerations of MCDA tool; (3) development and customization of MCDA tool and (4) policy implementation of MCDA in decision-making. Expert commentary: These practical MCDA recommendations for developing countries contribute to feasible, transparent, stepwise, iterative and standardized decision-making in health care.

A Targeted Literature Review Examining Biologic Therapy Compliance and Persistence in Chronic Inflammatory Diseases to Identify the Associated Unmet Needs, Driving Factors, and Consequences.

Chronic inflammatory diseases (CIDs) represent a substantial clinical and economic burden to patients, providers, payers and society overall. Biologics, such as tumor necrosis factor inhibitors (TNFi), have emerged as effective treatment options for patients with CIDs. However, the therapeutic potential of biologics is not always achieved in clinical practice, with results from studies examining the use of biologics in real-world settings suggesting lower levels of treatment effectiveness compared with clinical trial results. Using a targeted approach, this literature review demonstrates that compliance and persistence with biologic therapy is suboptimal and that this has implications for both clinical outcomes and treatment costs. The review identified a variety of predictors of treatment compliance and persistence, including increased age, female gender, presence of comorbidities, increased disease activity, longer disease duration, smoking, increased body mass index, higher biologic treatment dose, higher treatment cost and lower health-related quality-of-life scores. Patients often cited factors associated with medication delivery as a reason for non-compliance and non-persistence, and device-related improvements to treatment delivery were associated with higher rates of compliance and persistence. The articles identified in this review provide insights that have the potential to help guide the development of new solutions to improve disease management and optimize treatment regimens. This has the potential to benefit patients' health by improving clinical outcomes and to reduce the burden to society by limiting the economic impact of patients' disease. FUNDING: UCB Pharma.

An Evidence Framework for Off-Patent Pharmaceutical Review for Health Technology Assessment in Emerging Markets.

OBJECTIVE: This article introduces an Evidence Framework for Off-Patent Pharmaceutical Review (EFOR), which establishes value-based criteria in a template that manufacturers use to provide evidence showing how their products meet those criteria. Health authorities in emerging markets can then use the evidence presented in the EFOR to evaluate off-patent pharmaceuticals (OPPs) in a consistent, transparent, and evidence-based manner to support policy decisions, including pricing, reimbursement, formulary listing, and drug procurement. METHODS: A literature search found no multi-criteria evidence framework for evaluating OPPs in emerging markets. An International Outcomes Research Board (IORB) of academia and industry experts conducted extensive research, meetings, and workshops to define high-priority criteria to incorporate into an evidence-based health technology assessment (HTA) tool using the multi-criteria decision analysis (MCDA) technique. The resulting framework was further tailored for country-specific needs in workshops in three emerging countries (Kazakhstan, Vietnam, and Indonesia). RESULTS: The IORB defined nine criteria four categories (Product, Manufacturing, Service, and Value Assessment), which OPP manufacturers can use to provide evidence for reimbursement and health policy decision making. Then the IORB developed the EFOR as a base case document, which can be adapted and used as a template by health authorities in emerging countries. CONCLUSIONS: Emerging countries have a significant need for an HTA tool that balances affordability with accurate evidence showing the value differentiation of OPPs. The value attributes in this setting often are different from those in developed markets, which emphasize new products and have high regulation and manufacturing standards. The EFOR is an easy-to-use, adaptable framework that emerging countries can use to increase the consistency, transparency, and effectiveness of drug decision making. The open source EFOR is available as Supplemental Materials.

Cost-Effectiveness of Empagliflozin for the Treatment of Patients with Type 2 Diabetes Mellitus at Increased Cardiovascular Risk in Greece.

BACKGROUND AND OBJECTIVE: Type 2 diabetes mellitus (T2DM) is frequently associated with co-morbidities that exacerbate cardiovascular (CV) risk. CV disease is the leading cause of death in people with diabetes across the world and accounts for approximately half the deaths in the T2DM population. Hence, the objective of present study was to evaluate the cost-effectiveness of empagliflozin, in addition to standard of care (SoC), for the treatment of adult patients with T2DM and high CV risk in Greece. METHODS: A health economic model was used to project clinical and economic outcomes of patients receiving empagliflozin plus SoC compared with those receiving SoC alone over a lifetime horizon. CV and renal event rates were derived from patient level data from the EMPA-REG-OUTCOME® trial by fitting time-dependent parametric survival functions. 5000 individual patient profiles randomly sampled from the trial were simulated using a time-to-event approach. Model extrapolated outcomes included life years (LYs), quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratio (ICER). Following a Greek third-party payer perspective, only direct medical costs related to drug acquisition as well as fatal and non-fatal diabetes-related complications were considered (€2016). Cost units and utility data were extracted from the literature and publicly available official sources. Sensitivity analyses explored the impact of changes in input data. RESULTS: Over a patient's lifetime, empagliflozin was predicted to result in longer mean survival (14.01 LY vs. 11.87 LY with SoC) and reduced rate of clinical events accumulating 7.75 QALYs versus 6.83 QALYs on SoC alone at additional costs of €4235. The generated ICER of empagliflozin was €4633 per QALY gained. One-way sensitivity analysis confirmed empagliflozin's cost-effective profile. At the defined willingness-to-pay threshold of €34,000 per QALY gained, probabilistic sensitivity analysis showed that empagliflozin was estimated to have a 100% probability of being cost-effective relative to SoC. CONCLUSIONS: Empagliflozin added to SoC was estimated to be a highly cost-effective treatment option for the treatment of T2DM in adults with increased CV disease risk in Greece.

Cost Effectiveness of Exenatide Once Weekly Versus Insulin Glargine and Liraglutide for the Treatment of Type 2 Diabetes Mellitus in Greece.

OBJECTIVE: The objective of this study was to evaluate the long-term cost effectiveness of exenatide once weekly (ExQW) versus insulin glargine (IG) or liraglutide 1.2 mg (Lira1.2mg) for the treatment of adult patients with type 2 diabetes mellitus (T2DM) not adequately controlled on oral antidiabetic drug (OAD) therapy in Greece. METHODS: The published and validated Cardiff Diabetes Model was used to project clinical and economic outcomes over a patient's lifetime. Clinical data were retrieved from a head-to-head clinical trial (DURATION 3) and a published network meta-analysis comparing ExQW with IG or Lira1.2mg, respectively. Following a Greek third-party payer perspective, direct medical costs related to drug acquisition, consumables, developed micro- and macrovascular complications, maintenance treatment, as well as treatment-related adverse events were considered. Cost and utility data were extracted from literature and publicly available official sources and assigned to model parameters to calculate total quality-adjusted life-years (QALYs) and total costs as well as incremental cost-effectiveness ratios (ICERs). Sensitivity analyses explored the impact of changes in input data. RESULTS: Over a patient's lifetime, ExQW was associated with 0.458 or 0.039 incremental QALYs compared with IG or Lira1.2mg, respectively, at additional costs of €2061 or €110, respectively. The ICER for ExQW was €4499/QALY compared with IG and €2827/QALY compared with Lira1.2mg. Results were robust across various one-way and scenario analyses. At the defined willingness-to-pay threshold of €36,000/QALY, probabilistic sensitivity analysis showed that ExQW had a 100 or 88.2% probability of being cost effective relative to IG or Lira1.2mg, respectively. CONCLUSIONS: ExQW was estimated to be cost effective relative to IG or Lira1.2mg for the treatment of T2DM in adults not adequately controlled on OAD therapy in Greece.

Applying Multi-Criteria Decision Analysis (MCDA) Simple Scoring as an Evidence-based HTA Methodology for Evaluating Off-Patent Pharmaceuticals (OPPs) in Emerging Markets.

Off-patent pharmaceuticals (OPPs) represent more than 60% of the pharmaceutical market in many emerging countries, where they are frequently evaluated primarily on cost rather than with health technology assessment. OPPs are assumed to be identical to the originators. Branded and unbranded generic versions can, however, vary from the originator in active pharmaceutical ingredients, dosage, consistency formulation, excipients, manufacturing processes, and distribution, for example. These variables can alter the efficacy and safety of the product, negatively impacting both the anticipated cost savings and the population's health. In addition, many health care systems lack the resources or expertise to evaluate such products, and current assessment methods can be complex and difficult to adapt to a health system's needs. Multicriteria decision analysis (MCDA) simple scoring is an evidence-based health technology assessment methodology for evaluating OPPs, especially in emerging countries in which resources are limited but decision makers still must balance affordability with factors such as drug safety, level interchangeability, manufacturing site and active pharmaceutical ingredient quality, supply track record, and real-life outcomes. MCDA simple scoring can be applied to pharmaceutical pricing, reimbursement, formulary listing, and drug procurement. In November 2015, a workshop was held at the International Society for Pharmacoeconomics and Outcomes Research Annual Meeting in Milan to refine and prioritize criteria that can be used in MCDA simple scoring for OPPs, resulting in an example MCDA process and 22 prioritized criteria that health care systems in emerging countries can easily adapt to their own decision-making processes.

Cost-Effectiveness Analysis of Rivaroxaban for Treatment of Deep Vein Thrombosis and Pulmonary Embolism in Greece.

BACKGROUND AND OBJECTIVE: Venous thromboembolism (VTE), comprising deep-vein thrombosis (DVT) and pulmonary embolism (PE), is a major healthcare concern that results in substantial morbidity and mortality with great economic burden for healthcare systems. Hence, the need for effective and efficient treatment of patients with VTE is important for both clinical and economic reasons. The objective of this study was to evaluate the cost effectiveness of rivaroxaban compared to standard of care (SoC) with enoxaparin followed by dose-adjusted vitamin-K antagonists for the treatment of DVT and PE in Greece. METHODS: An existing Markov model was locally adapted from a third-party payer perspective to reflect the management and complications of DVT and PE in the course of 3-month cycles, up to death. The clinical inputs and utility values were extracted from published studies. Direct medical costs, obtained from local resources, were incorporated in the model and refer to year 2017. Both costs and outcomes were discounted at 3.5%. The incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) gained was calculated. Probabilistic sensitivity analysis (PSA) was carried out to deal with uncertainty. RESULTS: The base-case analysis showed that rivaroxaban in 3- and 6-month treatment duration for DVT and PE, respectively, as this is the common clinical practice in Greece, was associated with a 0.02 and 0.01 increment in QALYs compared to SoC, respectively. Rivaroxaban was associated with a reduced total cost in DVT (€85) but with an additional total cost in PE (€2) compared to SoC. Therefore, rivaroxaban was a dominant (less costly, more effective) and cost-effective (ICER: €177) alternative over SoC for the management of DVT and PE, respectively. PSA revealed that the probability of rivaroxaban being cost effective at a threshold of €34,000 per QALY gained was 99% and 81% for DVT and PE, respectively. CONCLUSION: Rivaroxaban may represent a cost-effective option relative to SoC for the management of DVT and PE in Greece.

Economic evaluation of trimetazidine in the management of chronic stable angina in Greece.

BACKGROUND: To evaluate the cost-effectiveness of trimetazidine (TMZ) as add-on therapy to standard-of-care (SoC) compared to SoC alone in patients with chronic stable angina who did not respond adequately to first line therapy with b-blockers, nitrates or calcium channel antagonists in Greece. METHODS: A Markov model with 3-month cycles and 1-year time horizon was developed to assess the comparators. The analysis was conducted from a third-party payer perspective. The clinical inputs and utility values were extracted from the published literature. Resource consumption data were obtained from local experts, using a questionnaire developed for the purpose of the study and were combined with unit cost data (in €2016) obtained from official sources. Cost effectiveness was assessed by calculating the incremental cost effectiveness ratio (ICER). Probabilistic sensitivity analysis (PSA) was performed to account for uncertainty and variation in the input parameters of the model. RESULTS: The analysis showed that the cost of TMZ plus SoC was €1755.57 versus €1751.76 of SoC alone. In terms of health outcomes, TMZ plus SoC was associated with 0.6650 QALYs versus 0.6562 QALYs for SoC alone. The incremental analysis resulted in an ICER of €430.67 per QALY gained. PSA revealed that the probability of TMZ plus SoC being cost-effective over SoC was 89 %, at a threshold of €34,000 per QALY gained. CONCLUSION: The results indicate that TMZ as add -on treatment may be a highly cost-effective option for the symptomatic treatment of patients with chronic stable angina in Greece relative to SoC alone.

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.

Cost-Effectiveness of Dapagliflozin as Add-On to Metformin for the Treatment of Type 2 Diabetes Mellitus in Greece.

BACKGROUND AND OBJECTIVE: Type 2 diabetes mellitus (T2DM) is a chronic progressive disease that has been spread worldwide over the past three decades and associated with increased morbidity and mortality resulting in considerable socioeconomic implications for national healthcare systems. Effective management of disease is highly needed ensuring patients receive the best possible care within the available budget. The objective of this study was to evaluate the long-term cost-effectiveness of dapagliflozin, a sodium-glucose co-transporter-2 (SGLT-2) inhibitor, compared with a sulfonylurea (SU) or a dipeptidyl-peptidase-4 inhibitor (DPP-4i), when added to metformin, in T2DM patients inadequately controlled on metformin alone in Greece. METHODS: The published and validated Cardiff diabetes model, a lifetime micro-simulation model, was adapted to a Greek healthcare setting to determine the incidence of micro- and macro-vascular complications and diabetes-specific and all-cause mortality. Clinical, cost, and utility data were retrieved from literature and assigned to model parameters to calculate total quality-adjusted life-years (QALYs) and total costs as well as incremental cost-effectiveness ratios (ICERs). The analysis was conducted from the perspective of a third-party payer in Greece. Uncertainty surrounding important model parameters was explored with univariate and probabilistic sensitivity analyses (PSA). RESULTS: Over a patient's lifetime, dapagliflozin was associated with 0.48 and 0.04 incremental QALYs compared with SU and DPP-4i, respectively, at additional costs of €5142 and €756, respectively. The corresponding ICERs were €10,623 and €17,695 per QALY gained versus the treatment with SU and DPP-4i, respectively. Results were robust across various univariate and scenario analyses. At the defined willingness-to-pay threshold of €34,000 per QALY gained, PSA estimated that treatment with dapagliflozin had a 100 % and 79.7 % probability of being cost-effective relative to the SU and DPP-4i treatments. CONCLUSIONS: Dapagliflozin in combination with metformin was shown to be a cost-effective treatment alternative for patients with T2DM whose metformin regimen does not provide sufficient glycemic control in a Greek healthcare setting.

Cost-utility of ranibizumab versus aflibercept for treating Greek patients with visual impairment due to diabetic macular edema.

BACKGROUND: To conduct a cost-utility analysis of ranibizumab versus aflibercept for the treatment of patients with visual impairment due to diabetic macular edema (DME) in the Greek setting. METHODS: A Markov model was adapted to compare the use of ranibizumab 0.5 mg (pro re nata-PRN and treat and extend-T&E) to aflibercept 2 mg (every 8 weeks after five initial doses) in DME. Patients transitioned at a 3-month cycle among nine specified health states (including death) over a lifetime horizon. Transition probabilities, utilities, as well as DME-related mortality were extracted from relevant clinical trials, a network meta-analysis and other published studies. The analysis was conducted from payer perspective and as such only costs reimbursed by the payer were considered (year 2014). The incremental cost per quality-adjusted life year (QALY) gained and the net monetary benefit was the main outcome measures. RESULTS: Τhe use of PRN and T&E ranibizumab regimens were shown to be cost saving comparing to aflibercept (by €2824 and €22, respectively), and more beneficial in terms of QALYs gained (+0.05) and time without visual impairment (0.031 and 0.034 years), thereby dominating aflibercept. Moreover, ranibizumab used as PRN or T&E resulted in a net monetary benefit of €3984 and €1278, respectively. CONCLUSIONS: Both PRN and T&E ranibizumab regimens were more beneficial and less costly compared to aflibercept for the management of DME. Hence, ranibizumab seems to be a dominant option for the treatment of visual impairment due to DME in the Greek setting.

A literature review to evaluate the economic value of ranolazine for the symptomatic treatment of chronic angina pectoris.

To conduct a systematic review of the evidence regarding the economic value of ranolazine relative to standard-of-care (SOC) for the treatment of symptomatic chronic stable angina (CSA). Electronic databases were searched using relevant keywords. The identified studies were independently reviewed by two investigators against pre-determined inclusion and exclusion criteria. Their data were extracted using a relevant form and consequently were synthesized. Studies were also evaluated using the Quality of Health Economic Studies scale. The main outcomes considered were the cost and effectiveness for each comparator and the incremental cost per quality-adjusted-life year (QALY) gained. Six studies were included in the review. Five of these assessed the cost-utility of ranolazine added to SOC, compared to SOC alone, using decision trees or Markov models whereas one was a retrospective cost evaluation study. The analysis was conducted from a payer perspective in five studies and from a societal perspective in one study with the time horizon varying between six months and a year. The incremental cost-effectiveness ratio (ICER), ranged from €4000 to €15,000 per QALY gained. Ranolazine appears to be dominant or cost-effective, mainly due to its ability to decrease angina-related hospitalizations and also due to a marginal improvement in quality of life. The acquisition cost of ranolazine was the variable with the greatest impact upon the ICER. The existing evidence, although limited, indicates that ranolazine may be a dominant or cost-effective therapy option, for the treatment of patients with symptomatic CSA. Further research is required to evaluate the cost-effectiveness of ranolazine.