Cost-effectiveness analysis of pharmacogenomics-guided clopidogrel treatment in Spanish patients undergoing percutaneous coronary intervention.

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.

Performance Ratio Based Resource Allocation Decision-Making in Genomic Medicine.

In modern healthcare systems, the available resources may influence the morbidity, mortality, and-consequently-the level of healthcare provided in every country. This is of particular interest in developing countries where the resources are limited and must be spent wisely to address social justice and the right for equal access in healthcare services by all the citizens in economically viable terms. In this light, the current allocation is, in practice, inefficient and rests mostly on each country's individual political and historical context and, thus, does not always incorporate decision-making enabled by economic models. In this study, we present a new economic model, specifically for resource allocation for genomic medicine, based on performance ratio, with potential applications in diverse healthcare sectors, which are particularly appealing for developing countries and low-resource environments. The model proposes a new method for resource allocation taking into account (1) the size of innovation of a new technology, (2) the relative effectiveness in comparison with social preferences, and (3) the cost of the technology, which permits the measurement of effectiveness to be determined differently in the context of a specific disease and then to be expressed in a relative form using a common performance ratio. The present work expands on previous work for innovation in economic models pertaining to genomic medicine and supports translational science.

Economic analysis of pharmacogenomic-guided clopidogrel treatment in Serbian patients with myocardial infarction undergoing primary percutaneous coronary intervention.

INTRODUCTION: Clopidogrel, which is activated by the CYP2C19 enzyme, is among the drugs for which all major regulatory agencies recommend genetic testing to be performed to identify a patient's CYP2C19 genotype in order to determine the optimal antiplatelet therapeutic scheme. The CYP2C19*2 and CYP2C19*3 variants are loss-of-function alleles, leading to abolished CYP2C19 function and thus have the risk of thrombotic events for carriers of these alleles on standard dosages, while the CYP2C19*17 allele results in CYP2C19 hyperactivity. AIMS: Here, we report our findings from a retrospective study to assess whether genotyping for the CYP2C19*2 allele was cost effective for myocardial infarction patients receiving clopidogrel treatment in the Serbian population compared with the nongenotype-guided treatment. RESULTS: We found that 59.3% of the CYP2C19*1/*1 patients had a minor or major bleeding event versus 42.85% of the CYP2C19*1/*2 and *2/*2, while a reinfarction event occurred only in 2.3% of the CYP21C9*1/*1 patients, compared with 11.2% of the CYP2C19*1/*2 and CYP2C19*2/*2 patients. There were subtle differences between the two patient groups, as far as the duration of hospitalization and rehabilitation is concerned, in favor of the CYP2C19*1/*1 group. The mean cost for the CYP2C19*1/*1 patients was estimated at €2547 versus €2799 in the CYP2C19*1/*2 and CYP2C19*2/*2 patients. Furthermore, based on the overall CYP2C19*1/*2 genotype frequencies in the Serbian population, a break-even point analysis indicated that performing the genetic test prior to drug prescription represents a cost-saving option, saving €13 per person on average. CONCLUSION: Overall, our data demonstrate that pharmacogenomics-guided clopidogrel treatment may represent a cost-saving approach for the management of myocardial infarction patients undergoing primary percutaneous coronary intervention in Serbia.

An Alternative Methodological Approach for Cost-Effectiveness Analysis and Decision Making in Genomic Medicine.

Genomic Medicine aims to improve therapeutic interventions and diagnostics, the quality of life of patients, but also to rationalize healthcare costs. To reach this goal, careful assessment and identification of evidence gaps for public health genomics priorities are required so that a more efficient healthcare environment is created. Here, we propose a public health genomics-driven approach to adjust the classical healthcare decision making process with an alternative methodological approach of cost-effectiveness analysis, which is particularly helpful for genomic medicine interventions. By combining classical cost-effectiveness analysis with budget constraints, social preferences, and patient ethics, we demonstrate the application of this model, the Genome Economics Model (GEM), based on a previously reported genome-guided intervention from a developing country environment. The model and the attendant rationale provide a practical guide by which all major healthcare stakeholders could ensure the sustainability of funding for genome-guided interventions, their adoption and coverage by health insurance funds, and prioritization of Genomic Medicine research, development, and innovation, given the restriction of budgets, particularly in developing countries and low-income healthcare settings in developed countries. The implications of the GEM for the policy makers interested in Genomic Medicine and new health technology and innovation assessment are also discussed.

Economic evaluation of pharmacogenomic-guided warfarin treatment for elderly Croatian atrial fibrillation patients with ischemic stroke.

BACKGROUND & METHODS: Economic evaluation in genomic medicine is an emerging discipline to assess the cost-effectiveness of genome-guided treatment. Here, we developed a pharmaco-economic model to assess whether pharmacogenomic (PGx)-guided warfarin treatment of elderly ischemic stroke patients with atrial fibrillation in Croatia is cost effective compared with non-PGx therapy. The time horizon of the model was set at 1 year. RESULTS: Our primary analysis indicates that 97.07% (95% CI: 94.08-99.34%) of patients belonging to the PGx-guided group have not had any major complications, compared with the control group (89.12%; 95% CI: 84.00-93.87%, p < 0.05). The total cost per patient was estimated at €538.7 (95% CI: €526.3-551.2) for the PGx-guided group versus €219.7 (95% CI: €137.9-304.2) for the control group. In terms of quality-adjusted life-years (QALYs) gained, total QALYs was estimated at 0.954 (95% CI: 0.943-0.964) and 0.944 (95% CI: 0.931-0.956) for the PGx-guided and the control groups, respectively. The true difference in QALYs was estimated at 0.01 (95% CI: 0.005-0.015) in favor of the PGx-guided group. The incremental cost-effectiveness ratio of the PGx-guided versus the control groups was estimated at €31,225/QALY. CONCLUSION: Overall, our data indicate that PGx-guided warfarin treatment may represent a cost-effective therapy option for the management of elderly patients with atrial fibrillation who developed ischemic stroke in Croatia.

Cost-effectiveness analysis of ranibizumab versus verteporfin photodynamic therapy, pegaptanib sodium, and best supportive care for the treatment of age-related macular degeneration in Greece.

BACKGROUND: Age-related macular degeneration (AMD) is a progressive disease that results in loss of central vision, significant functional impairment, and a subsequent heavy socioeconomic burden. AMD treatments delay disease progression, improve patient outcomes, and reduce resource use associated with visual impairment, however, in a varying way concerning costs and effects. OBJECTIVE: The purpose of this study was to investigate the cost effectiveness of ranibizumab compared with verteporfin photodynamic therapy, pegaptanib sodium, and best supportive care for the treatment of AMD in Greece. METHODS: A 6-state Markov model was constructed according to patient visual acuity in the better-seeing eye. Data on effectiveness were derived from randomized controlled trials evaluating the outcomes of ranibizumab versus alternative AMD treatments. Resource utilization reflected the Greek health care setting and was defined by a panel of experts. All treatments were administered for a 2-year period and evaluated during a 10-year time frame from a third-party payer perspective and discounted at 3.5% per annum. RESULTS: Estimated mean 10-year direct costs of treatment in the ranibizumab arm ranged from €23,733 to €31,795 (2011 Euros), with a projected gain of 4.50 to 4.74 quality-adjusted life years (QALYs) or 2.97 to 4.47 vision years, depending on type of lesion. For predominantly classic lesions, the cost per QALY gained with ranibizumab was estimated at €6444/QALY (95% uncertainty interval [UI], €-30,403/QALY to €44,524/QALY), €15,344 (95% UI, €-11,433 to €53,554) and dominant relative to photodynamic therapy, best supportive care, and pegaptanib, respectively. Corresponding ratios for patients with minimally classic lesions were €24,580/QALY (95% UI, €-5580/QALY to €76,229/QALY) and €13,112/QALY (95% UI, €-3839/QALY to €37,527/QALY) for ranibizumab relative to best supportive care and pegaptanib, and for patients with occult lesions were estimated at €19,407/QALY (95% UI, €-1486 to €46,434) and €28,561/QALY (95% UI, €6143 to 73,431), respectively. Sensitivity analysis provided robust results in all cases. CONCLUSION: Ranibizumab can be a cost-effective option for the treatment of AMD compared with selected alternatives in the Greek health care setting.

Economic evaluation of irbesartan in combination with hydrochlorothiazide in the treatment of hypertension in Greece.

OBJECTIVES: Hypertension is a major risk factor for cardiovascular disease and a leading cause of morbidity and mortality. This study evaluates irbesartan in relation to commonly used alternative hypertension therapies losartan and valsartan given in combination with hydrochlorothiazide (HCTZ) in the general hypertensive population in Greece. METHODS: A Markov model with eight states of health was constructed: hypertension, myocardial infarction (MI), post-MI, angina, stroke, poststroke, heart failure, and death. The model has an annual cycle and estimates mean quality-adjusted survival and treatment cost, which reflect the hypertension treatment and managing cardiovascular events. Risk functions were used to conduct extrapolations. Data on treatment effectiveness, quality of life (QOL) and epidemiology were obtained from published clinical trials and studies. The database of the main Greek National Social Insurance Institute (IKA) was analyzed to estimate the cost of events. The analysis was done from a payer perspective. All outcomes were discounted, and prices correspond to 2008. RESULTS: The estimated patient cost per annum was stable angina euro 2,252, unstable angina euro 2,572, myocardial infarction euro 2,473, post-MI euro 1,677, stroke euro 12,233, poststroke euro 1,240, heart failure euro 2,655, coronary angiography euro 1,544, percutaneous transluminal coronary angioplasty euro 6,511, and coronary artery bypass graft surgery euro 11,514. For the baseline group (age 57 years, systolic blood pressure 147 mmHg, cholesterol 6.00 mmol/L, body mass index 29) of men with mild to moderate hypertension, for irbesartan, the total treatment cost was euro 15,146, for losartan euro 15,696 and for valsartan euro 15,613; the quality-adjusted life years (QALYs) were irbesartan 12.67, losartan 12.63 and valsartan 12.64. For the baseline group of women with mild to moderate hypertension, the total treatment cost was euro 12,945 for irbesartan, euro 13,424 for losartan and euro 13,379 for valsartan; QALYs were 14.29 for irbesartan, 14.27 for losartan and 14.27 for valsartan. For men with severe hypertension, for irbesartan and losartan, the total treatment cost was euro 18,679 and euro 21,488 and QALYs 12.47 and 12.37, respectively. For women, the total treatment cost was euro 16,202 and euro 19,099 and QALYs 14.16 and 14.09, respectively. Similar results were obtained in relation to other treatment groups in various sensitivity analysis scenarios. CONCLUSIONS: Based on efficacy data from clinical trials and lower attainment costs in various hypertensive patient populations, irbesartan in combination with HCTZ compares favorably with losartan and valsartan in combination with HCTZ in the Greek setting.

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

OBJECTIVES: An economic analysis (based on interim data from a long-term, randomised, multi-centre, controlled, clinical trial) to evaluate chemotherapy with XELOX (capecitabine/oxaliplatin) versus FOLFOX6 (5Fluorouracil/leucovorin/oxaliplatin) as an adjuvant treatment for high risk colorectal cancer patients in Greece. METHODS: As survival rate was the same in the two arms, a cost-minimisation analysis was carried out, from the perspectives of the National Health Service (NHS), Social Insurance Funds (SIF) and patients in Greece. Patient data were combined with 2008 unit prices to estimate the total cost of patient care, the patients' travelling expenditure and their productivity losses. Raw data were bootstrapped 5000 times in order to allow statistical testing. RESULTS: From an NHS perspective, the mean chemotherapy cost was 8762 euro with FOLFOX6 and 9713 euro with XELOX; costs of administration and hospitalisations were 5154 euro and 1050 euro, respectively. Total treatment cost with FOLFOX6 reached 17,480 euro and with XELOX 12 525 euro, a difference of 4955 euro (p < 0.001) in favour of the latter therapy. From an SIF perspective, the total cost of treatment was 16,240 euro with FOLFOX6 and 12,617 euro with XELOX, a reduction of 3623 euro (p < 0.001) with the latter therapy. Mean patient travelling cost was 184 euro with FOLFOX6 and 80 euro with XELOX, a difference of 104 euro (p < 0.001). Mean productivity loss was 100 euro with FOLFOX6 and 31 euro with XELOX, a difference of 69 euro (p < 0.001). CONCLUSIONS: Chemotherapy combining oral capecitabine and oxaliplatin reduces total treatment cost for the Greek National Health Service and Social Insurance Funds, mainly through a reduction in the cost of administration. From patients' perspective, it reduces travelling expenditure and productivity losses. Therefore, this combination may be a cost-effective approach for the management of colorectal cancer patients who have had surgery in Greece. This is an analysis alongside a clinical trial, and should be interpreted in this specific context in which it was undertaken.