Clinical implications and cost-effectiveness analysis of rivaroxaban in patients with coronary artery disease or peripheral arterial disease in the Netherlands.

BACKGROUND: Patients with stable coronary artery disease (CAD) or peripheral artery disease (PAD) are at substantial risk of atherothrombotic events. The COMPASS trial showed that patients with stable CAD or PAD experienced significant benefits after treatment with rivaroxaban in combination with acetylsalicylic acid (ASA) compared with ASA alone. This paper aims to provide insight into the clinical and economic consequences of treatment with rivaroxaban from a Dutch societal perspective. METHODS: The clinical and economic implications of rivaroxaban in terms of the number of events prevented, costs, the incremental cost per life-years gained (LYG), and incremental cost per quality-adjusted life-years (QALYs) were determined based on a cost-effectiveness model for patients with stable CAD or PAD and in high-risk subgroups (i.e. patients with CAD and PAD, CAD and prior myocardial infarction and renal impairment, CAD and heart failure) using results from the Cardiovascular OutcoMes for People Using Anticoagulation Strategies (COMPASS) trial. RESULTS: Patients treated with rivaroxaban have an expected increased discounted life expectancy of 0.67 years. In high-risk groups discounted incremental life expectancy ranged from 1.33 to 1.90 years. The incremental cost-effectiveness ratio for the full COMPASS population was €9,760/LYG and €12,033/QALY, whereas, for high-risk subgroups of patients with underlying conditions, incremental cost-effectiveness ratios ranged from €2,966/LYG to €5,052/LYG and from €3,940/QALY to €6,815/QALY. Results from the sensitivity analyses revealed that the model results were robust to variations in single or multiple input parameters at once. CONCLUSIONS: The cost-effectiveness analysis showed that rivaroxaban in combination with ASA is a cost-effective treatment option in stable CAD or PAD patients. Rivaroxaban in combination with ASA is even more cost-effective in high-risk subgroups.

Cost-effectiveness analysis of exenatide once-weekly versus dulaglutide, liraglutide, and lixisenatide for the treatment of type 2 diabetes mellitus: an analysis from the UK NHS perspective.

OBJECTIVE: To assess the cost-effectiveness of exenatide 2 mg once-weekly (EQW) compared to dulaglutide 1.5 mg QW, liraglutide 1.2 mg and 1.8 mg once-daily (QD), and lixisenatide 20 µg QD for the treatment of adult patients with type 2 diabetes mellitus (T2DM) not adequately controlled on metformin. METHODS: The Cardiff Diabetes Model was applied to evaluate cost-effectiveness, with treatment effects sourced from a network meta-analysis. Quality-adjusted life years (QALYs) were calculated with health-state utilities applied to T2DM-related complications, weight changes, hypoglycemia, and nausea. Costs (GBP £) included drug treatment, T2DM-related complications, severe hypoglycemia, nausea, and treatment discontinuation due to adverse events. A 40-year time horizon was used. RESULTS: In all base-case comparisons, EQW was associated with a QALY gain per patient; 0.046 vs dulaglutide 1.5 mg; 0.102 vs liraglutide 1.2 mg; 0.043 vs liraglutide 1.8 mg; and 0.074 vs lixisenatide 20 µg. Cost per patient was lower for EQW than for liraglutide 1.8 mg (-£2,085); therefore, EQW dominated liraglutide 1.8 mg. The cost difference per patient between EQW and dulaglutide 1.5 mg, EQW and liraglutide 1.2 mg, and EQW and lixisenatide 20 µg was £27, £103, and £738, respectively. Cost per QALY gained with EQW vs dulaglutide 1.5 mg, EQW vs liraglutide 1.2 mg, and EQW vs lixisenatide 20 µg was £596, £1,004, and £10,002, respectively. In the probabilistic sensitivity analysis, the probability that EQW is cost-effective ranged from 76-99%. CONCLUSION: Results suggest that exenatide 2 mg once-weekly is cost-effective over a lifetime horizon compared to dulaglutide 1.5 mg QW, liraglutide 1.2 mg QD, liraglutide 1.8 mg QD, and lixisenatide 20 µg QD for the treatment of T2DM in adults not adequately controlled on metformin alone.

Patient and physician preferences for oral pharmacotherapy for overactive bladder: two discrete choice experiments.

OBJECTIVE: We examined patient and treating physician (general practitioners, urologists, and [uro]gynecologists) preferences for oral pharmacotherapy (antimuscarinics and beta-3 adrenoceptor agonists) for overactive bladder to gain a deeper understanding of which attributes drive their treatment decision-making and to quantify to what extent. RESEARCH DESIGN AND METHODS: Two separate discrete choice experiments were developed and validated using the input of patients and physicians. The patient experiment contained the following attributes: micturition frequency, incontinence, nocturia, urgency, dry mouth, constipation, increased heart rate, and increased blood pressure. The physician experiment contained two additional attributes: coping and atrial fibrillation. Both were fielded in five European countries. To allow for preference heterogeneity, utility functions were estimated using a mixed multinomial logit model. RESULTS: A total of 442 patient and 318 physician responses were analyzed. Patients ranked the attributes based on their largest potential impact on treatment value as follows: incontinence, nocturia, risk of an increased heart rate, urgency, frequency, risk of increased blood pressure, risk of constipation, and risk of dry mouth; and physicians as follows: incontinence, urgency, nocturia, frequency, risk of dry mouth, coping, risk of increased heart rate, risk of increased blood pressure, risk of atrial fibrillation, and risk of constipation. CONCLUSION AND LIMITATIONS: In their valuations, physicians put more emphasis on increasing benefits, whereas patients put more emphasis on limiting risks of side effects. Another contrast that emerged was that patients' valuations of side effects were found to be fairly insensitive to the presented risk levels (with the exception of risk of dry mouth), whereas physicians' evaluated all side effects in a risk-level dependent manner. The obtained utility functions can be used to predict whether, to what extent, and for which reasons patients and physicians would choose one oral pharmacotherapy over another, as well as to advance shared decision-making.

Methods applied in cost-effectiveness models for treatment strategies in type 2 diabetes mellitus and their use in Health Technology Assessments: a systematic review of the literature from 2008 to 2013.

OBJECTIVE: To identify and compare health-economic models that were developed to evaluate the cost-effectiveness of treatments for type 2 diabetes mellitus (T2DM), and their use within Health Technology Assessments (HTAs). METHODS: In total, six commonly used databases were searched for articles published between October 2008 and January 2013, using a protocolized search strategy and inclusion criteria. The websites of HTA organizations in nine countries, and proceedings from five relevant conferences, were also reviewed. The identified new health-economic models were qualitatively assessed using six criteria that were developed based on technical components, and characteristics related to the disease or the treatments being assessed. Finally, the number of times the models were applied within HTA reports, published literature, and/or major conferences was determined. RESULTS: Thirteen new models were identified and reviewed in depth. Most of these were based on identical key data sources, and applied a similar model structure, either using Markov modeling or microsimulation techniques. The UKPDS equations and panel regressions were frequently used to estimate the occurrence of diabetes-related complications and the probability of developing risk factors in the long term. The qualitative assessment demonstrated that the CARDIFF, Sheffield T2DM and ECHO T2DM models seem technically equipped to appropriately assess the long-term health-economic consequences of chronic treatments for patients with T2DM. It was observed that the CORE model is the most widely described in literature and conferences, and the most often applied model within HTA submissions, followed by the CARDIFF and UKPDS models. CONCLUSION: This research provides an overview of T2DM models that were developed between 2008 and January 2013. The outcomes of the qualitative assessments, combined with frequent use in local reimbursement decisions, prove the applicability of the CORE, CARDIFF and UKPDS models to address decision problems related to the long-term clinical and economic consequences of new and existing T2DM treatments.

Cost-effectiveness of 3-year vs 1-year adjuvant therapy with imatinib in patients with high risk of gastrointestinal stromal tumour recurrence in the Netherlands; a modelling study alongside the SSGXVIII/AIO trial.

BACKGROUND: Surgical resection of gastrointestinal stromal tumour (GIST) is rarely curative in patients at high risk of tumour recurrence and therefore 1 year of post-surgery adjuvant imatinib therapy has been recommended in this sub-group. Recently, adjuvant imatinib therapy administered for 3 years has been demonstrated to further increase recurrence-free survival and overall survival. The goal of this study was to assess the economic value of extending the duration of adjuvant imatinib therapy in high-risk patients in the Netherlands. METHODS: A multistate Markov model was developed to simulate how patients' clinical status after GIST excision evolves over time until death. The model structure encompassed four primary health states: free of recurrence, first GIST recurrence, second GIST recurrence, and death. Transition probabilities between the health states, data on medical care costs, and quality-of-life were obtained from published sources and from expert opinion. RESULTS: The expected number of life years (or quality-adjusted life years, QALYs) was higher in the 3-year group than in the 1-year group, 8.91 (6.55) and 7.04 (5.18) years, respectively. In the 3-year and 1-year group, the expected total costs amounted to €120,195 and €79,361, of which, €74,631 (62%) and €27,619 (35%) were adjuvant therapy drug costs, respectively. The difference in health benefits, that is 1.87 life years or 1.37 QALYs, and costs, €40,835, resulted in incremental cost-effectiveness ratios (ICER) of €21,865 per life year gained, and €29,872 per QALY gained. LIMITATIONS: A limitation of the study was inherently related to the uncertainty around the predictions of RFS. Scenario analyses were conducted to test the sensitivity of different RFS predictions on the results. CONCLUSIONS: Delayed recurrence due to treatment with longer-term adjuvant imatinib therapy represents a cost-effective treatment option with an ICER below the generally accepted threshold in the Netherlands.

Fingolimod reduces direct medical costs compared to natalizumab in patients with relapsing-remitting multiple sclerosis in The Netherlands.

OBJECTIVE: To assess the costs of oral treatment with Gilenya® (fingolimod) compared to intravenous infusion of Tysabri® (natalizumab) in patients with relapsing-remitting multiple sclerosis (RRMS) in The Netherlands. METHODS: A cost-minimization analysis was used to compare both treatments. The following cost categories were distinguished: drug acquisition costs, administration costs, and monitoring costs. Costs were discounted at 4%, and incremental model results were presented over a 1, 2, 5, and 10 year time horizon. The robustness of the results was determined by means of a number of deterministic univariate sensitivity analyses. Additionally, a break-even analysis was carried out to determine at which natalizumab infusion costs a cost-neutral outcome would be obtained. RESULTS: Comparing fingolimod to natalizumab, the model predicted discounted incremental costs of -€2966 (95% CI: -€4209; -€1801), -€6240 (95% CI: -€8800; -€3879), -€15,328 (95% CI: -€21,539; -€9692), and -€28,287 (95% CI: -€39,661; -€17,955) over a 1, 2, 5, and 10-year time horizon, respectively. These predictions were most sensitive to changes in the costs of natalizumab infusion. Changing these costs of €255 within a range from €165-364 per infusion resulted in cost savings varying from €4031 to €8923 after 2 years. The additional break-even analysis showed that infusion costs-including aseptic preparation of the natalizumab solution-needed to be as low as the respective costs of €94 and €80 to obtain a cost neutral result after 2 and 10 years. LIMITATIONS: Neither treatment discontinuation and subsequent re-initiation nor patient compliance were taken into account. As a consequence of the applied cost-minimization technique, only direct medical costs were included. CONCLUSION: The present analysis showed that treatment with fingolimod resulted in considerable cost savings compared to natalizumab: starting at €2966 in the first year, increasing to a total of €28,287 after 10 years per RRMS patient in the Netherlands.

Cost effectiveness analysis of immunotherapy in patients with grass pollen allergic rhinoconjunctivitis in Germany.

OBJECTIVES: An economic evaluation was conducted to assess the outcomes and costs as well as cost-effectiveness of the following grass-pollen immunotherapies: OA (Oralair; Stallergenes S.A., Antony, France) vs GRZ (Grazax; ALK-Abelló, Hørsholm, Denmark), and ALD (Alk Depot SQ; ALK-Abelló) (immunotherapy agents alongside symptomatic medication) and symptomatic treatment alone for grass pollen allergic rhinoconjunctivitis. METHODS: The costs and outcomes of 3-year treatment were assessed for a period of 9 years using a Markov model. Treatment efficacy was estimated using an indirect comparison of available clinical trials with placebo as a common comparator. Estimates for immunotherapy discontinuation, occurrence of asthma, health state utilities, drug costs, resource use, and healthcare costs were derived from published sources. The analysis was conducted from the insurant's perspective including public and private health insurance payments and co-payments by insurants. Outcomes were reported as quality-adjusted life years (QALYs) and symptom-free days. The uncertainty around incremental model results was tested by means of extensive deterministic univariate and probabilistic multivariate sensitivity analyses. RESULTS: In the base case analysis the model predicted a cost-utility ratio of OA vs symptomatic treatment of €14,728 per QALY; incremental costs were €1356 (95%CI: €1230; €1484) and incremental QALYs 0.092 (95%CI: 0.052; 0.140). OA was the dominant strategy compared to GRZ and ALD, with estimated incremental costs of -€1142 (95%CI: -€1255; -€1038) and -€54 (95%CI: -€188; €85) and incremental QALYs of 0.015 (95%CI: -0.025; 0.056) and 0.027 (95%CI: -0.022; 0.075), respectively. At a willingness-to-pay threshold of €20,000, the probability of OA being the most cost-effective treatment was predicted to be 79%. Univariate sensitivity analyses show that incremental outcomes were moderately sensitive to changes in efficacy estimates. The main study limitation was the requirement of an indirect comparison involving several steps to assess relative treatment effects. CONCLUSION: The analysis suggests OA to be cost-effective compared to GRZ and ALD, and a symptomatic treatment. Sensitivity analyses showed that uncertainty surrounding treatment efficacy estimates affected the model outcomes.

The influence of small aerosol particles on the properties of water and ice clouds.

In this paper, results are presented of the influence of small organic- and soot-containing particles on the formation of water and ice clouds. There is strong evidence that these particles have grown from nano particle seeds produced by the combustion of oil products. Two series of field experiments are selected to represent the observations made. The first is the CLoud-Aerosol Characterisation Experiment (CLACE) series of experiments performed at a high Alpine site (Jungfraujoch), where cloud was in contact with the ground and the measuring station. Both water and ice clouds were examined at different times of the year. The second series of experiments is the CLOud Processing of regional Air Pollution advecting over land and sea (CLOPAP) series, where ageing pollution aerosol from UK cities was observed, from an airborne platform, to interact with warm stratocumulus cloud in a cloud-capped atmospheric boundary layer. Combining the results it is shown that aged pollution aerosol consists of an internal mixture of organics, sulfate, nitrate and ammonium, the organic component is dominated by highly oxidized secondary material. The relative contributions and absolute loadings of the components vary with location and season. However, these aerosols act as Cloud Condensation Nuclei (CCN) and much of the organic material, along with the other species, is incorporated into cloud droplets. In ice and mixed phase cloud, it is observed that very sharp transitions (extending over just a few metres) are present between highly glaciated regions and regions consisting of supercooled water. This is a unique finding; however, aircraft observations in cumulus suggest that this kind of structure may be found in these cloud types too. It is suggested that this sharp transition is caused by ice nucleation initiated by oxidised organic aerosol coated with sulfate in more polluted regions of cloud, sometimes enhanced by secondary ice particle production in these regions.