Background:The objective of this study was to compare the cost-effectiveness of the fixed-dose combination (FDC) of tiotropium + olodaterol Respimat® FDC with tiotropium alone for patients with chronic obstructive pulmonary disease (COPD) in the Italian health care setting using a newly developed patient-level Markov model that reflects the current understanding of the disease.Methods:While previously published models have largely been based around a cohort approach using a Markov structure and GOLD stage stratification, an individual-level Markov approach was selected for the new model. Using patient-level data from the twin TOnado trials assessing Tiotropium + olodaterol Respimat® FDC versus tiotropium, outcomes were modelled based on the trough forced expiratory volume (tFEV1) of over 1000 patients in each treatment arm, tracked individually at trial visits through the 52-week trial period, and after the trial period it was assumed to decline at a constant rate based on disease stage. Exacerbation risk was estimated based on a random-effects logistic regression analysis of exacerbations in UPLIFT. Mortality by age and disease stage was estimated from an analysis of TIOSPIR trial data. Cost of bronchodilators and other medications, routine management, and costs of treatment for moderate and severe exacerbations for the Italian setting were included. A cost-effectiveness analysis was conducted over a 15-year time horizon from the perspective of the Italian National Health Service.Results:Aggregating total costs and quality-adjusted life years (QALYs) for each treatment cohort over 15 years and comparing tiotropium + olodaterol Respimat® FDC with tiotropium alone, resulted in mean incremental costs per patient of €1167 and an incremental cost-effectiveness ratio (ICER) of €7518 per additional QALY with tiotropium + olodaterol Respimat® FDC. The lung function outcomes observed for tiotropium + olodaterol Respimat® FDC in TOnado drove the results in terms of slightly higher mean life-years (12.24 versus 12.07) exacerbation-free months (11.36 versus 11.32) per patient and slightly fewer moderate and severe exacerbations per patient-year (0.411 versus 0.415; 0.21 versus 0.24) versus tiotropium. Probabilistic sensitivity analyses showed tiotropium + olodaterol Respimat® FDC to be the more cost-effective treatment in 95.2% and 98.4% of 500 simulations at thresholds of €20,000 and €30,000 per QALY respectively.Conclusion:Tiotropium + olodaterol Respimat® FDC is a cost-effective bronchodilator in the maintenance treatment of COPD for the Italian health care system.

To develop a health economic model that included a great diversity of patient characteristics and outcomes for chronic obstructive pulmonary disease (COPD), which can be used to inform decisions about stratified medicine in COPD. Methods: The choice of patient characteristics and outcomes to include in the model was based on 3 literature reviews on multidimensional prognostic COPD indices, COPD phenotypes, and treatment effects in subgroups. A conceptual model was constructed including 14 patient characteristics, 7 intermediate outcomes (lung function, physical activity, exercise capacity, symptoms, disease-specific quality of life, exacerbations, and pneumonias), and 3 final outcomes (mortality, quality-adjusted life-years [QALYs], and costs). Regression equations describing the statistical associations between the patient characteristics and intermediate and final outcomes were estimated using the longitudinal data of 5 large COPD trials (19,378 patients). A patientlevel simulation model was developed in which individual patients from the baseline population of the 5 trials are sampled and their outcomes over lifetime are predicted based on the regression equations. Results: The base-case analysis (single-arm simulation representing treatment with tiotropium) showed that patients had a mean lung function decline of 43 mL/year, 0.62 exacerbations/year, a worsening of their physical activity and quality of life with 1.48 and 1.10 points/year, a life expectancy of 11.2 years, 7.25 QALYs, and total lifetime costs of £24,891. Results for a selection of treatment scenarios and subgroups were shown to demonstrate the potential of the model. Conclusions: We developed a unique patient-level simulation model that can be used to evaluate COPD treatment options for a variety of subgroups.

receptor antagonists (57.1%) and biologic treatment (omalizumab) (39.3%). 139 patients (45.9%) had at least one exacerbation (mean: 1.9 exacerbation/patient), of whom 22 patients required hospitalization, with a mean hospital stay of 10.9 days/ patient. Mean sick leave due to severe asthma was 9.15 days per patient. Mean annual direct cost (confidence interval 95%) was € 7,393 (6,509-8,514) per patient. 62.4% of the cost was due to omalizumab treatment. The cost per exacerbation was € 1,195/patient. When indirect costs were added (€ 856/patient (476-1,573)), the total annual mean cost rose to € 8,250/patient (7,193-9,733). ConClusions: The economic impact of severe asthma in Spain amounts to 8,250€ /patient from the societal perspective.

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Objectives: The 9.5 version of IQVIA-CORE-Diabetes-Model (CDM) includes a simplified foot ulcer (FU) submodel. The current study aims to explain the differences between the new and previous FU submodel and assess their impact on health economic outputs. Methods: The updated FU submodel is a five-health-state Markov Model (no history of ulcer, active ulcer, history of ulcer, history of amputation, death) with an annual cycle length, using the UKPDS82 risk equations (user defined inputs are optional). The previous FU submodel comprised nine health-states with monthly cycles and included options of screening and several treatment types. To test this update, cohorts were simulated with baseline characteristics and treatment effects from the observational EDGE study comparing metformin+vildagliptin (M+V) with metformin+sulphonylurea (M+S), with mean age of 57.8 years and time horizon of 50 years. Patients had no history of ulcer and amputation. Cumulative Incidence (CI) of FU complications, total and quality-adjusted life years (LY, QALY) were determined. The economic analysis employed UK 2018 costs and applied an annual discount rate of 3.5% on costs and outcomes. Results: The updated FU model leads to moderate differences in first ulcer CI (M+V: 2.86% to 3.45%; M+S: 2.90% to 3.64%) and amputation rate (M+V: 1.10% to 0.82%; M+S: 1.08% to 0.85%). Changes benefit the most effective arm, which also reflects in a limited difference in costs between the two arms (10 GBP). FU-related costs are reduced (M+V: -4.67%; M+S: -1.12%). The new model results in higher LY (M+V: +0.224; M+S: +0.258) and QALY (M+V: +0.038; M+S: +0.052), mainly due to the updated renal submodel, which reduces end-stage renal disease CI (M+V: 9.91% to 2.39%; M+S 10.03% to 2.41%). The Incremental Cost-Utility Ratio (ICUR) increases from 8,455 to 10,410 GBP/QALY. Conclusions: Using the simplified ulcer model of v9.5 CDM results in small differences in FU-related incidence, benefiting the most effective treatment arm.