Cost-effectiveness analysis of defibrotide in the treatment of patients with severe veno-occlusive disease/sinusoidal obstructive syndrome with multiorgan dysfunction following hematopoietic cell transplantation in Spain.

AIMS: This study evaluated cost-effectiveness of defibrotide vs best supportive care (BSC) for the treatment of hepatic veno-occlusive disease/sinusoidal obstructive syndrome (VOD/SOS) with multiorgan dysfunction (MOD) post-hematopoietic cell transplantation (HCT) in Spain. MATERIALS AND METHODS: A two-phase Markov model, comprising a 1-year acute phase with daily cycles and a lifetime long-term phase with annual cycles, was adapted to the Spanish setting. The model included a cohort of patients with severe VOD/SOS (defined as VOD/SOS with MOD) post-HCT. For the acute phase, efficacy and VOD/SOS-related length of stay were obtained from a phase 3 defibrotide study (NCT00358501). VOD/SOS-related hospital stays were 7.5 and 23.2 days in defibrotide-treated and BSC patients, respectively. Defibrotide-treated patients spent 30% of their stay in the intensive care unit vs 60% in BSC patients. Assumptions for the long-term phase and utility values were obtained from the literature. Costs were from the Spanish Health System perspective (€2019). Defibrotide cost was based on 25 mg/kg/day over 17.5 days, using local expert opinion. Life-years (LYs), quality-adjusted LYs (QALYs), and costs were estimated over a lifetime horizon, applying a 3% discount rate for costs and outcomes. Sensitivity analyses assessed the robustness of the results. RESULTS: Defibrotide produced an additional 1.214 QALYs and 1.348 LYs vs BSC, with a total cost of €33,708 more than BSC alone. However, defibrotide resulted in savings up to €16,644/patient for cost of hospital stay. Difference between costs and effective measures led to ratios of €27,757/QALY and €25,007/LY gained. Additional hospital stays had the greatest influence on base-case results. Probabilistic analysis confirmed the robustness of the deterministic results. LIMITATIONS: Limitations include use of historical controls and assumptions extrapolated from the literature. CONCLUSIONS: This cost-effectiveness model, adapted to the Spanish setting, showed that defibrotide is a cost-effective alternative to BSC alone in patients with severe VOD/SOS post-HCT.

Budget Impact Analysis of Biosimilar Products in Spain in the Period 2009-2019.

Since the first biosimilar medicine, Omnitrope® (active substance somatropin) was approved in 2006, 53 biosimilars have been authorized in Spain. We estimate the budget impact of biosimilars in Spain from the perspective of the National Health System (NHS) over the period between 2009 and 2019. Drug acquisition costs considering commercial discounts at public procurement procedures (hospital tenders) and uptake data for both originator and biosimilar as actual units consumed by the NHS were the two variables considered. Two scenarios were compared: a scenario where no biosimilars are available and the biosimilar scenario where biosimilars are effectively marketed. All molecules exposed to biosimilar competition during this period were included in the analysis. The robustness of the model was tested by conducting multiple sensitivity analyses. From the payer perspective, it is estimated that the savings produced by the adoption of biosimilars would reach EUR 2306 million over 11 years corresponding to the cumulative savings from all biosimilars. Three molecules (infliximab, somatropin and epoetin) account for 60% of the savings. This study provides the first estimation of the financial impact of biosimilars in Spain, considering both the effect of discounts that manufacturers give to hospitals and the growing market share of biosimilars. We estimate that in our last year of data, 2019, the savings derived from the use of biosimilars relative total pharmaceutical spending in Spain is 3.92%. Although more research is needed, our evidence supports the case that biosimilars represent a great opportunity to the sustainability of the NHS through rationalizing pharmaceutical spending and that the full potential of biosimilar-savings has not been achieved yet, as there is a high variability in biosimilar uptake across autonomous regions.

Estimation of the Clinical and Economic Impact of an Improvement in Adherence Based on the Use of Once-Daily Single-Inhaler Triple Therapy in Patients with COPD.

Background: Adherence to treatment is key to achieve desired outcomes. In COPD, adherence is generally suboptimal and is impaired by treatment complexity. Objective: To estimate the clinical and economic impact of an improvement in treatment adherence due to an increased use of once-daily single-inhaler triple therapy (SITT) in patients with COPD. Patients and Methods: A 7-state Markov model with monthly cycles was developed. Patients with moderate-to-very severe COPD, for whom triple therapy is indicated, were included. Outcomes and costs were estimated and compared for two scenarios: current distribution of adherent patients treated with multiple inhaler triple therapies (MITT) vs a potential scenario where patients shifted to once-daily SITT. In the potential scenario, adherence improvement due to once-daily SITT attributes was estimated. Costing was based on the Spanish National Health System (NHS) perspective (€2019). A 3-year time horizon was defined considering a 3% discount rate for both costs and outcomes. Results: A target population of 185,111 patients with moderate-to-very severe COPD currently treated with MITT was estimated. A 20% increase in the use of once-daily SITT in the potential scenario raised adherence up to 52%. This resulted in 6835 exacerbations and 532 deaths avoided, with 775 LYs and 594 QALYs gained. Total savings reached €7,082,105. Exacerbation reduction accounted for 61.8% (€4,378,201) of savings. Conclusion: Increasing the use of once-daily SITT in patients with moderate-to-very severe COPD treated with triple therapy would be associated with an improvement in adherence, a reduction of exacerbations and deaths, and cost savings for the Spanish NHS.

Cost-effectiveness of combination therapy umeclidinium/vilanterol versus tiotropium in symptomatic COPD Spanish patients.

PURPOSE: Umeclidinium/vilanterol (UMEC/VI) is a novel fixed dose combination of a long-acting muscarinic receptor antagonist (LAMA) and a long-acting beta 2 receptor antagonist (LABA) agent. This analysis evaluated the incremental cost-effectiveness ratio (ICER) of UMEC/VI compared with tiotropium (TIO), from the Spanish National Health System (NHS) perspective. METHODS: A previously published linked equations cohort model based on the epidemiological longitudinal study ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points) was used. Patients included were COPD patients with a post-bronchodilator forced expiratory volume in 1 second (FEV1) ≤70% and the presence of respiratory symptoms measured with the modified Medical Research Council dyspnea scale (modified Medical Research Council ≥2). Treatment effect, expressed as change in FEV1 from baseline, was estimated from a 24-week head-to-head phase III clinical trial comparing once-daily UMEC/VI with once-daily TIO and was assumed to last 52 weeks following treatment initiation (maximum duration of UMEC/VI clinical trials). Spanish utility values were derived from a published local observational study. Unitary health care costs (€2015) were obtained from local sources. A 3-year time horizon was selected, and 3% discount was applied to effects and costs. Results were expressed as cost/quality-adjusted life years (QALYs). Univariate and probabilistic sensitivity analysis (PSA) was performed. RESULTS: UMEC/VI produced additional 0.03 QALY and €590 vs TIO, leading to an ICER of €21,475/QALY. According to PSA, the probability of UMEC/VI being cost-effective was 80.3% at a willingness-to-pay of €30,000/QALY. CONCLUSION: UMEC/VI could be considered as a cost-effective treatment alternative compared with TIO in symptomatic COPD patients from the Spanish NHS perspective.

Treatment patterns, resource use and costs of idiopathic pulmonary fibrosis in Spain--results of a Delphi Panel.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a form of chronic fibrosing interstitial pneumonia characterized by progressive worsening of dyspnea and lung function, with a poor prognosis. The objective of this study was to determine treatment patterns, resource use and costs of managing Spanish patients with IPF. METHODS: A three-round Delphi consensus panel of 15 clinical experts was held between December 2012 and June 2013 using questionnaires to describe the management of patients with IPF. A cost analysis based on Delphi panel estimates was made from the Spanish National Health System (NHS) perspective, including the direct costs of IPF diagnosis and management. Unit costs were applied to Delphi panel estimates of health resource use. Univariate sensitivity analyses were made to evaluate uncertainties in parameters. RESULTS: The Delphi panel estimated that 20, 60 and 20% of IPF patients presented with stable disease, slow and rapid disease progression, respectively. The estimated annual cost per patient with stable disease, slow and rapid disease progression was €11,484, €20,978 and €57,759, respectively. This corresponds to a weighted average annual cost of €26,435 with itemized costs of €1,184 (4.5), €7,147 (27.0), €5,950 (22.5), €11,666 (44.1) and €488 (1.9%) for the diagnosis of IPF, treatment, monitoring, management of acute exacerbations and end-of-life care, respectively. The parameter that varied the annual cost per patient the most was resource use associated with acute exacerbations. CONCLUSIONS: The management of patients with IPF in Spain, especially patients with rapid disease progression, has a high economic impact on the NHS.

Orphan drugs revisited: cost-effectiveness analysis of the addition of mifamurtide to the conventional treatment of osteosarcoma.

INTRODUCTION: Mepact(®) (mifamurtide) is the first drug approved for the treatment of high-grade resectable non-metastatic osteosarcoma in patients aged 2-30 in the last 20 years. It follows a randomized clinical trial showing a statistically-significant and clinically-relevant decrease in the risk of death without compromising safety. AIM: This study assessed the cost-effectiveness and budget impact of mifamurtide. METHODS: The economic evaluation was done on a hypothetical cohort of young patients under the age of 30 with high-grade, non-metastatic, resectable osteosarcoma. Standard chemotherapy without mifamurtide was used as comparator. A Markov model was adapted using Spanish costs and the results of the INT-0133 Phase III study. The analysis has been carried out from the perspective of the Spanish National Health Service, with a time horizon of up to 60 years in the base analysis. RESULTS: The observed greater efficacy of mifamurtide in the trial translates into a gain of 3.03 (undiscounted) and 1.33 (discounted) quality-adjusted life years at an additional cost of €102,000. The estimated budgetary impact of using mifamurtide in 10-100% of the potential population would cost €671,000 and €6.7 million respectively. CONCLUSION: The cost per quality-adjusted life years gained with mifamurtide in Spain is in the low band (<€100,000) of the iCERs obtained by other orphan drugs and would have a limited and affordable cost in Spain.