RESUMEN
BACKGROUND: This was an updated network meta-analysis (NMA) of anti-vascular endothelial growth factor (VEGF) agents and laser photocoagulation in patients with diabetic macular edema (DME). Unlike previous NMA that used meta-regression to account for potential confounding by systematic variation in treatment effect modifiers across studies, this update incorporated individual patient-level data (IPD) regression to provide more robust adjustment. METHODS: An updated review was conducted to identify randomised controlled trials for inclusion in a Bayesian NMA. The network included intravitreal aflibercept (IVT-AFL) 2 mg bimonthly (2q8) after 5 initial doses, ranibizumab 0.5 mg as-needed (PRN), ranibizumab 0.5 mg treat-and-extend (T&E), and laser photocoagulation. Outcomes included in the analysis were change in best-corrected visual acuity (BCVA), measured using an Early Treatment Diabetic Retinopathy Study (ETDRS) chart, and patients with ≥10 and ≥ 15 ETDRS letter gains/losses at 12 months. Analyses were performed using networks restricted to IPD-only and IPD and aggregate data with (i) no covariable adjustment, (ii) covariable adjustment for baseline BVCA assuming common interaction effects (against reference treatment), and (iii) covariable adjustments specific to each treatment comparison (restricted to IPD-only network). RESULTS: Thirteen trials were included in the analysis. IVT-AFL 2q8 was superior to laser in all analyses. IVT-AFL 2q8 showed strong evidence of superiority (95% credible interval [CrI] did not cross null) versus ranibizumab 0.5 mg PRN for mean change in BCVA (mean difference 5.20, 95% CrI 1.90-8.52 ETDRS letters), ≥15 ETDRS letter gain (odds ratio [OR] 2.30, 95% CrI 1.12-4.20), and ≥10 ETDRS letter loss (OR 0.25, 95% CrI 0.05-0.74) (IPD and aggregate random-effects model with baseline BCVA adjustment). IVT-AFL 2q8 was not superior to ranibizumab 0.5 mg T&E for mean change in BCVA (mean difference 5.15, 95% CrI -0.26-10.61 ETDRS letters) (IPD and aggregate random-effects model). CONCLUSIONS: This NMA, which incorporated IPD to improve analytic robustness, showed evidence of superiority of IVT-AFL 2q8 to laser and ranibizumab 0.5 mg PRN. These results were irrespective of adjustment for baseline BCVA.
Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Bevacizumab/uso terapéutico , Retinopatía Diabética/terapia , Coagulación con Láser/métodos , Edema Macular/terapia , Ranibizumab/uso terapéutico , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéutico , Humanos , Inyecciones Intravítreas , Edema Macular/fisiopatología , Metaanálisis en Red , Oportunidad Relativa , Ensayos Clínicos Controlados Aleatorios como Asunto , Análisis de Regresión , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Agudeza Visual/fisiologíaRESUMEN
OBJECTIVE: The aim of the study was to estimate the burden and direct medical costs of unintended pregnancy to the public payer in Spain. METHODS: An economic model evaluating the costs and outcomes of contraceptive use over a 1-year period was constructed for women in Spain aged 15 to 44 years at risk of pregnancy. Model inputs were derived from published literature and national survey data. Outcomes evaluated included: (i) the annual number of unintended pregnancy events and their cost; (ii) the proportion of unintended pregnancy events and their cost due to non-adherence; and (iii) the use and cost of contraceptive methods in Spain. RESULTS: Of the total number of pregnancies, 35% are estimated to be unintended and are associated with a direct cost burden of 292.8 million per year. Most unintended pregnancies (26%) occur in women aged 30 to 34 years, whilst 69% of the total cost burden is estimated to be attributable to poor adherence to contraceptive methods. CONCLUSIONS: The cost associated with unintended pregnancy is high. The major proportion of the burden is estimated to be attributable to imperfect adherence and is likely avoidable. Shifts in patterns of contraceptive use, combined with measures to improve adherence, could have a substantial and positive impact on this burden.
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Costos Directos de Servicios/estadística & datos numéricos , Embarazo no Planeado , Adolescente , Adulto , Anticoncepción/economía , Conducta Anticonceptiva/estadística & datos numéricos , Costos y Análisis de Costo , Femenino , Humanos , Cooperación del Paciente/estadística & datos numéricos , Embarazo , España , Adulto JovenRESUMEN
OBJECTIVE: Dulaglutide 1.5 mg once weekly is a novel glucagon-like peptide 1 (GLP-1) receptor agonist, for the treatment of type two diabetes mellitus (T2DM). The objective was to estimate the cost-effectiveness of dulaglutide once weekly vs liraglutide 1.8 mg once daily for the treatment of T2DM in Spain in patients with a BMI ≥30 kg/m2. METHODS: The IMS CORE Diabetes Model (CDM) was used to estimate costs and outcomes from the perspective of Spanish National Health System, capturing relevant direct medical costs over a lifetime time horizon. Comparative safety and efficacy data were derived from direct comparison of dulaglutide 1.5 mg vs liraglutide 1.8 mg from the AWARD-6 trial in patients with a body mass index (BMI) ≥30 kg/m2. All patients were assumed to remain on treatment for 2 years before switching treatment to basal insulin at a daily dose of 40 IU. One-way sensitivity analyses (OWSA) and probabilistic sensitivity analyses (PSA) were conducted to explore the sensitivity of the model to plausible variations in key parameters and uncertainty of model inputs. RESULTS: Under base case assumptions, dulaglutide 1.5 mg was less costly and more effective vs liraglutide 1.8 mg (total lifetime costs 108,489 vs 109,653; total QALYS 10.281 vs 10.259). OWSA demonstrated that dulaglutide 1.5 mg remained dominant given plausible variations in key input parameters. Results of the PSA were consistent with base case results. LIMITATIONS: Primary limitations of the analysis are common to other cost-effectiveness analyses of chronic diseases like T2DM and include the extrapolation of short-term clinical data to the lifetime time horizon and uncertainty around optimum treatment durations. CONCLUSION: The model found that dulaglutide 1.5 mg was more effective and less costly than liraglutide 1.8 mg for the treatment of T2DM in Spain. Findings were robust to plausible variations in inputs. Based on these results, dulaglutide may result in cost savings to the Spanish National Health System.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Péptidos Similares al Glucagón/análogos & derivados , Hipoglucemiantes/economía , Fragmentos Fc de Inmunoglobulinas/economía , Liraglutida/economía , Proteínas Recombinantes de Fusión/economía , Anciano , Índice de Masa Corporal , Simulación por Computador , Análisis Costo-Beneficio , Complicaciones de la Diabetes/economía , Complicaciones de la Diabetes/prevención & control , Esquema de Medicación , Honorarios Farmacéuticos/estadística & datos numéricos , Femenino , Péptido 1 Similar al Glucagón/antagonistas & inhibidores , Péptidos Similares al Glucagón/economía , Péptidos Similares al Glucagón/uso terapéutico , Hemoglobina Glucada/efectos de los fármacos , Servicios de Salud/economía , Servicios de Salud/estadística & datos numéricos , Humanos , Hipoglucemiantes/uso terapéutico , Fragmentos Fc de Inmunoglobulinas/uso terapéutico , Liraglutida/uso terapéutico , Masculino , Cadenas de Markov , Persona de Mediana Edad , Modelos Econométricos , Años de Vida Ajustados por Calidad de Vida , Proteínas Recombinantes de Fusión/uso terapéutico , EspañaRESUMEN
INTRODUCTION: Venous thromboembolism is a burden on healthcare systems. The aim of this analysis was to project the long-term costs and outcomes for rivaroxaban compared to standard of care (enoxaparin/warfarin) in Portugal for the treatment and secondary prevention of venous thromboembolism. MATERIAL AND METHODS: A Markov model was developed using event rates extracted from the EINSTEIN trials supplemented with literature-based estimates of longer-term outcomes. Core outcomes included per patient costs and quality-adjusted life years reported separately per treatment arm and incrementally, as well as cost per quality-adjusted life years gained. The deep vein thrombosis and pulmonary embolism indications were analysed separately. The analyses were conducted from the Portuguese societal perspective and over a 5-year time horizon. Costs and outcomes were discounted at a 5% annual rate. Several scenario analyses were undertaken to explore the impact on results of varying key modeling assumptions. RESULTS: Rivaroxaban treatment was associated with cost-savings for the treatment of deep vein thrombosis and was both cost-saving and more effective for the treatment of pulmonary embolism, compared with enoxaparin/warfarin. DISCUSSION: The results of the sensitivity and scenario analyses further supported that rivaroxaban is a cost-effective alternative to standard of care treatment. The use of an expert panel to derive some input values and the lack of Portuguese specific utilities were the main limitations. CONCLUSION: Rivaroxaban represents an efficient alternative to using enoxaparin/warfarin in Portugal, as it's associated with lower costs (for both indications) and greater quality adjusted life years (for the pulmonary embolism indication).
Introdução: O tromboembolismo venoso representa uma carga substancial para os sistemas de saúde. O objectivo foi estimar os resultados clínicos e económicos a longo-prazo associados a rivaroxabano relativamente à prática clínica (enoxaparina/varfarina) no tratamento e prevenção secundária de tromboembolismo venoso em Portugal.Material e Métodos: Foi desenvolvido um modelo de Markov baseado nos ensaios clínicos EINSTEIN e dados da literatura para complicações a longo-prazo. Foram avaliados custos e anos de vida ajustados pela qualidade de vida totais e incrementais e rácio custo-efectividade incremental. As indicações trombose venosa profunda e embolismo pulmonar foram analisados separadamente. Adoptou-se a perspectiva da sociedade portuguesa e um horizonte temporal de cinco anos. Aplicou-se uma taxa de actualização de cinco por cento para custos e consequências. Foram desenvolvidas análises de sensibilidade e diversas análises de cenário para avaliação da variação dos resultados em função de determinados pressupostos.Resultados: Rivaroxabano está associado a menores custos na trombose venosa profunda e constitui uma alternativa associada a menores custos e a maior eficácia no tratamento de embolismo pulmonar, relativamente a enoxaparina/varfarina.Discussão: O recurso a um painel de peritos para identificação de alguns recursos e a ausência de utilidades específicas para Portugal constituem as principais limitações.Conclusão: Rivaroxabano constitui uma alternativa eficaz, estando associado a menores custos (para ambas as indicações) e a mais anos de vida ajustados pela qualidade de vida (para embolismo pulmonar) relativamente a enoxaparina/varfarina em Portugal.
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Anticoagulantes/uso terapéutico , Costos y Análisis de Costo , Enoxaparina/uso terapéutico , Inhibidores del Factor Xa/economía , Rivaroxabán/economía , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/prevención & control , Warfarina/uso terapéutico , Inhibidores del Factor Xa/uso terapéutico , Humanos , Modelos Económicos , Portugal , Años de Vida Ajustados por Calidad de Vida , Rivaroxabán/uso terapéutico , Factores de TiempoRESUMEN
INTRODUCTION AND AIMS: To project the long-term cost-effectiveness of treating non-valvular atrial fibrillation (AF) patients for stroke prevention with rivaroxaban compared to warfarin in Portugal. METHODS: A Markov model was used that included health and treatment states describing the management and consequences of AF and its treatment. The model's time horizon was set at a patient's lifetime and each cycle at three months. The analysis was conducted from a societal perspective and a 5% discount rate was applied to both costs and outcomes. Treatment effect data were obtained from the pivotal phase III ROCKET AF trial. The model was also populated with utility values obtained from the literature and with cost data derived from official Portuguese sources. The outcomes of the model included life-years, quality-adjusted life-years (QALYs), incremental costs, and associated incremental cost-effectiveness ratios (ICERs). Extensive sensitivity analyses were undertaken to further assess the findings of the model. As there is evidence indicating underuse and underprescription of warfarin in Portugal, an additional analysis was performed using a mixed comparator composed of no treatment, aspirin, and warfarin, which better reflects real-world prescribing in Portugal. RESULTS: This cost-effectiveness analysis produced an ICER of 3895/QALY for the base-case analysis (vs. warfarin) and of 6697/QALY for the real-world prescribing analysis (vs. mixed comparator). The findings were robust when tested in sensitivity analyses. CONCLUSION: The results showed that rivaroxaban may be a cost-effective alternative compared with warfarin or real-world prescribing in Portugal.