Cost-effectiveness analysis of using innovative therapies for the management of moderate-to-severe ulcerative colitis in Spain.

BACKGROUND: To evaluate the cost-effectiveness of tofacitinib in comparison to vedolizumab for the treatment of moderate-to-severe ulcerative colitis (UC) after failure or intolerance to conventional therapy (bio-naive) or first-line biologic treatment (bio-experienced), from the Spanish National Health System (NHS) perspective. METHODS: A lifetime Markov model with eight-week cycles was developed including five health states: remission, response, active UC, remission after surgery, and death. Response and remission probabilities (for induction and maintenance periods) were obtained from a multinomial network meta-analysis. Drug acquisition - biosimilar prices included - (ex-factory price with mandatory deductions), administration, surgery, patient management, and adverse event management costs (€, year 2019) were considered. A 3% discount rate (cost/outcomes) was applied. Probabilistic and deterministic sensitivity analyses (PSA) were conducted. RESULTS: Tofacitinib was dominant versus vedolizumab (both in bio-naive and bio-experienced patients) entailing total cost savings of €23,816 (bio-naïve) and €11,438 (bio-experienced). Differences in quality-adjusted life-year (QALY) were smaller than 0.1 for both populations. PSA results showed that tofacitinib has a high probability of being cost-effective (bio-naïve: 82.5%; bio-experienced: 90.6%) versus vedolizumab. CONCLUSIONS: From the Spanish NHS perspective, tofacitinib could be a dominant treatment (less costly and more effective) in comparison to vedolizumab, with relevant cost savings and similar QALY gains.

A multi-stakeholder multicriteria decision analysis for the reimbursement of orphan drugs (FinMHU-MCDA study).

BACKGROUND: Patient access to orphan medicinal products (OMPs) is limited and varies between countries, reimbursement decisions on OMPs are complex, and there is a need for more transparent processes to know which criteria should be considered to inform these decisions. This study aimed to determine the most relevant criteria for the reimbursement of OMPs in Spain, from a multi-stakeholder perspective, and using multicriteria decision analysis (MCDA). METHODS: An MCDA was developed in 3 phases and included 28 stakeholders closely related to the field of rare diseases (6 physicians, 5 hospital pharmacists, 7 health economists, 4 patient representatives and 6 members from national and regional health authorities). Initially [phase A], a bibliographic review was conducted to identify the potential reimbursement criteria. Then, a reduced advisory board (8 members) proposed, selected, and defined the final list of criteria that could be relevant for reimbursement. A discrete choice experiment (DCE) [phase B] was developed to determine the relevance and relative importance weight of such criteria according to the stakeholders' preferences by choosing between pairs of hypothetical financing scenarios. A multinomial logit model was fitted to analyze the DCE responses. Finally [phase C], the advisory board review the results using a deliberative process. RESULTS: Thirteen criteria were selected, related to 4 dimensions: patient population, disease, treatment, and economic evaluation. Nine criteria were deemed relevant for decision-making and associated with a higher relative importance: Health-related quality of life (HRQL) (23.53%), treatment efficacy (14.64%), availability of treatment alternatives (13.51%), disease severity (12.62%), avoided costs (11.21%), age of target population (7.75%), safety (seriousness of adverse events) (4.72%), quality of evidence (3.82%) and size of target population (3.12%). The remaining criteria had a < 3% relative importance: economic burden of disease (2.50%), cost of treatment (1.73%), cost-effectiveness (0.83%) and safety (frequency of adverse events) (0.03%). CONCLUSION: The reimbursement of OMPs in Spain should be determined by its effect on patient's HRQL, the extent of its therapeutic benefit from efficacy and the availability of other therapeutic options. Furthermore, the severity of the rare disease should also influence the decision along with the potential of the treatment to avoid associated costs.

A Multiple Stakeholder Multicriteria Decision Analysis in Diabetic Macular Edema Management: The MULTIDEX-EMD Study.

BACKGROUND: The clinical and economic management of retinal diseases has become more complex following the introduction of new intravitreal treatments. Multicriteria decision analysis (MCDA) offers the potential to overcome the challenges associated with traditional decision-making tools. OBJECTIVES: A MCDA to determine the most relevant criteria to decision-making in the management of diabetic macular edema (DME) based on the perspectives of multiple stakeholders in Spain was developed. This MCDA was termed the MULTIDEX-EMD study. METHODS: Nineteen stakeholders (7 physicians, 4 pharmacists, 5 health authorities and health management experts, 1 psychologist, and 2 patient representatives) participated in this three-phase project. In phase A, an advisory board defined all of the criteria that could influence DME treatment decision-making. These criteria were then screened using a discrete choice experiment (DCE) (phase B). Next, a multinomial logit model was fitted by applying the backward elimination algorithm (relevant criteria: p value < 0.05). Finally, the results were discussed in a deliberative process (phase C). RESULTS: Thirty-one criteria were initially defined (phase A) and grouped into 5 categories: efficacy/effectiveness, safety, organizational and economic impact, patient-reported outcomes, and other therapeutic features. The DCE results (phase B) showed that 10 criteria were relevant to the decision-making process for a 50- to 65-year-old DME patient: mean change in best corrected visual acuity (p value < 0.001), percentage of patients with an improvement of ≥ 15 letters (p value < 0.001), effect duration per administration (p value = 0.008), retinal detachment (p value < 0.001), endophthalmitis (p value = 0.012), myocardial infarction (p value < 0.001), intravitreal hemorrhage (p value = 0.021), annual treatment cost per patient (p value = 0.001), health-related quality of life (HRQoL) (p value = 0.004), and disability level (p value = 0.021). CONCLUSIONS: From a multi-stakeholder perspective, the selection of an appropriate treatment for DME patients should guarantee patient safety and maximize the visual acuity improvement and treatment effect duration. It should also contribute to system sustainability by being affordable, it should have a positive impact on HRQoL, and it should prevent disability.

Cost-Effectiveness Analysis of Apixaban Versus Edoxaban in Patients with Atrial Fibrillation for Stroke Prevention.

OBJECTIVE: Our objective was to assess the cost effectiveness of apixaban versus edoxaban in the prevention of stroke and systemic embolism (SE) in patients with atrial fibrillation (AF) in Spain. METHODS: We customized a Markov model with ten health states to estimate the lifetime economic and clinical outcomes in 6-week cycles. The efficacy (clinical event rates per 100 patient-years) and safety data were derived from a pairwise indirect treatment comparison. The analysis was conducted from both the national health service (NHS) and societal perspectives, and included pharmaceutical costs (retail price plus value-added tax (VAT) and applicable national deductions) according to daily dosages (apixaban 10 mg (5 mg twice daily (bid)) and edoxaban 60 or 30 mg) and complications and disease-management costs, obtained from national databases. Utilities for quality-adjusted life-year (QALY) calculations reflected EuroQoL 5-Dimension scores in patients with AF. An annual discount rate of 3% was applied for costs (€, year 2019 values) and outcomes. RESULTS: In a 1000-patient cohort, apixaban 5 mg bid versus edoxaban 60 mg could avoid five strokes, six major bleedings and 29 clinically relevant non-major bleedings (CRNMBs). Compared with edoxaban 30 mg, apixaban could avoid 21 strokes and two SEs. An increase in bleedings was observed with apixaban (seven haemorrhagic strokes, 48 major bleedings and 17 CRNMBs). Apixaban yielded 0.04 additional QALYs compared with edoxaban 60 mg or 30 mg. Incremental costs/QALY were €9639.33 and €354.22 for apixaban versus edoxaban 60 mg and edoxaban 30 mg, respectively, from the NHS perspective and €7756.62 for apixaban versus edoxaban 60 mg from the societal perspective. Apixaban was dominant versus edoxaban 30 mg from the societal perspective. Sensitivity analyses confirmed the robustness of the model. CONCLUSIONS: This study suggests that apixaban 5 mg bid is a cost-effective alternative to edoxaban for stroke prevention in the AF population in Spain.

Budget impact analysis of dexamethasone intravitreal implant for the treatment of diabetic macular oedema.

OBJECTIVE: To assess the economic impact following the inclusion of an intravitreal implant of dexamethasone for the treatment of diabetic macular oedema in a healthcare area in Spain. METHOD: A 3-year budget impact model was designed to estimate healthcare  direct costs for adult patients with diabetic macular oedema from the National  Health System perspective. The approved therapies in use  (aflibercept/ranibizumab/dexamethasone) were considered. The target  population was estimated from published diabetic macular oedema prevalence  (6.41%) and incidence (0.82%) for a population of 25,000 adults.  Dexamethasone was assumed to be used annually in 20%, 30% and 40% of  patients, respectively. Annual total costs included: drug acquisition (based on  frequency of injections per every year, considering exfactory prices with  mandatory deduction and split of vials), intravitreal administration, patient  monitoring, management of cardiovascular and ocular adverse events  (cataracts, increased intraocular pressure, endophthalmitis, vitreous  haemorrhage and retinal detachment). Detailed resource consumption reflecting  clinical practice was provided from local experts in retina and vitreous. Unitary  costs (€, 2016) were obtained from national databases and literature. Sensitivity  analyses were performed to assess model robustness. RESULTS: The inclusion of intravitreal dexamethasone implant would lead to  annual cost savings of €35,030 (-4.2%), €10,743 (-1.8%) and €5,051 (-0.9%), years 1-3 respectively. Total costs were reduced mainly by the fewer annual  injections required by dexamethasone. The average annual incremental costs  were -€350, -€96 and -€41 per patient. CONCLUSIONS: The inclusion of an intravitreal dexamethasone implant for the  treatment of diabetic macular oedema would lead to cost-savings for the  considered health area, mainly by reducing the administration costs.

Objetivo: Determinar el impacto económico tras la inclusión del implante intravítreo de dexametasona para el tratamiento del edema macular diabético en un área sanitaria en España.Método: Se diseñó un modelo de impacto presupuestario a tres años para  estimar los costes directos en pacientes adultos con edema macular diabético,  desde la perspectiva del Sistema Nacional de Salud, considerando terapias  intravítreas actualmente utilizadas (aflibercept/ranibizumab/dexametasona). La  población diana se obtuvo a partir de la prevalencia (6,41%) e incidencia  (0,82%) del edema macular diabético publicadas para una población de 25.000  pacientes adultos. Se asumió un 20%, 30% y 40% anual de pacientes tratados  con dexametasona, respectivamente. El coste total incluyó: coste farmacológico  (precio de venta del laboratorio con deducción obligatoria y fraccionamiento de  viales, según frecuencia de inyecciones necesarias cada año de tratamiento),  administración intravítrea, seguimiento de pacientes y manejo de eventos  oculares (cataratas, hipertensión ocular, endoftalmitis, hemorragia intravítrea y  desprendimiento de retina) y cardiovasculares. El consumo de recursos según la  práctica habitual fue estimado por expertos en retina y vítreo. Los costes  unitarios (€, 2016) se obtuvieron de la literatura y de bases de datos nacionales.  Los análisis de sensibilidad evaluaron la robustez del modelo. Resultados: La inclusión del implante intravítreo de dexametasona supondría reducciones de 35.030 € (­4,2%), 10.743 € (­1,8%) y 5.051 € (­ 0,9%) cada año, respectivamente, disminuyendo principalmente por el menor  número anual de inyecciones requeridas con dexametasona. La reducción anual  promedio supondría 350 €, 96 € y 41 € por paciente.Conclusiones: La inclusión del implante intravítreo de dexametasona para el  tratamiento del edema macular diabético supone ahorros para el área sanitaria  considerada, fundamentalmente por la reducción de costes de administración.

Cost-effectiveness of mechanical thrombectomy using stent retriever after intravenous tissue plasminogen activator compared with intravenous tissue plasminogen activator alone in the treatment of acute ischaemic stroke due to large vessel occlusion in Spain.

INTRODUCTION: To assess the cost-effectiveness of stent-retriever mechanical thrombectomy and intravenous tissue plasminogen activator compared with intravenous tissue plasminogen activator alone in patients with acute ischaemic stroke due to large vessel occlusions in Spain. MATERIALS AND METHODS: Clinical data were taken from the SWIFT PRIME clinical trial. A lifetime Markov state transition model defined by the modified Rankin Scale score was developed to estimate costs and health outcomes (life years gained and quality adjusted life years). A Spanish National Health System perspective (direct medical costs) was considered. Resource utilisation and utilities were obtained from available published data and endorsed by an expert panel. Costs (€, 2016) were obtained from various Spanish sources. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: Stent-retriever thrombectomy after intravenous tissue plasminogen activator was associated with better outcomes (1.17 life years gained and 2.51 quality adjusted life years) and savings of €44,378, resulting in a dominant therapy over intravenous tissue plasminogen activator alone. A net monetary benefit of €119,744 was obtained considering a willingness-to-pay threshold of €30,000/quality adjusted life year gained. The combined therapy was also dominant in all sensitivity analyses, deterministic and probabilistic. DISCUSSION: The results were consistent with a previously published cost-effectiveness analysis and reinforce the likeliness of the selection of stent-retriever mechanical thrombectomy plus intravenous tissue plasminogen activator over intravenous tissue plasminogen activator alone. CONCLUSION: Stent-retriever thrombectomy after intravenous tissue plasminogen activator is a dominant alternative over intravenous tissue plasminogen activator alone (more effective and less costly) for the treatment of acute ischaemic stroke patients with large vessel occlusions in the Spanish setting.

Cost-effectiveness analysis of apixaban compared to low-molecularweight heparins and vitamin k antagonists for treatment and secondary prevention of venous thromboembolism.

OBJECTIVE: Cost-effectiveness analysis of a 6-month treatment of apixaban (10 mg/12h, first 7 days; 5 mg/12h afterwards) for the treatment of the first event of venous thromboembolism (VTE) and prevention of recurrences, versus low-molecular-weight heparins/vitamin K antagonists treatment (LMWH/VKA). MATERIAL AND METHODS: A lifetime Markov model with 13 health states was used for describing the course of the disease. Efficacy and safety data were obtained from AMPLIFY and AMPLIFY-EXT clinical trials; health outcomes were measured as life years gained (LYG) and quality-adjusted life years (QALY). The chosen perspective of this analysis has been the Spanish National Health System (NHS). Drugs, management of VTE and complications costs were obtained from several Spanish data sources (€, 2014). A 3% discount rate was applied to health outcomes and costs. Univariate and probabilistic sensitivity analyses (SA) were performed in order to assess the robustness of the results. RESULTS: Apixaban was the most effective therapy with 7.182 LYG and 5.865 QALY, versus 7.160 LYG and 5.838 QALYs with LMWH/VKA. Furthermore, apixaban had a lower total cost (€13,374.70 vs €13,738.30). Probabilistic SA confirmed dominance of apixaban (led to better health outcomes with less associated costs) in 89% of the simulations. CONCLUSIONS: Apixaban 5 mg/12h versus LMWH/VKA was an efficient therapeutic strategy for the treatment and prevention of recurrences of VTE from the NHS perspective.

Objetivo: Analizar la relación coste-efectividad de 6 meses de tratamiento con apixaban (10 mg/12 h, 7 primeros días; 5 mg/12 h después) para el primer evento de tromboembolismo venoso (TEV) y prevención de recurrencias, frente a heparinas de bajo peso molecular/antagonistas de vitamina K (HBPM/ AVK). Material y métodos: Se ha empleado un modelo de Markov con 13 estados de salud que describen la evolución de la enfermedad a lo largo de la vida de los pacientes. Los datos de eficacia y seguridad se han obtenido de los ensayos clínicos AMPLIFY y AMPLIFY- EXT, calculándose los años de vida ganados (AVG) y los años de vida ajustados por calidad (AVAC) de las opciones terapéuticas evaluadas. En este análisis se adoptó la perspectiva del Sistema Nacional de Salud (SNS). El coste de la medicación, de las complicaciones y del manejo del TEV se obtuvo de distintas fuentes españolas (€, 2014). Se aplicó una tasa de descuento anual del 3% a costes y beneficios en salud. Se realizaron análisis de sensibilidad univariante y probabilístico (ASP) para evaluar la robustez de los resultados. Resultados: Apixaban generó mejores resultados en salud con 7,182 AVG y 5,865 AVAC, frente a 7,160 AVG y 5,838 AVAC para HBPM/AVK, y con menor coste total (13.374,70 € versus 13.738,30 €). El ASP confirmó la dominancia de apixaban (produce mejores resultados con menores costes asociados) en el 89% de las simulaciones. Conclusiones: Apixaban 5 mg/12 h versus HBPM/AVK fue una estrategia eficiente para el SNS en el tratamiento y prevención de recurrencias de TEV.