An efficacy comparison of anti-vascular growth factor agents and laser photocoagulation in diabetic macular edema: a network meta-analysis incorporating individual patient-level data.

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.

Direct costs of unintended pregnancy in Spain.

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.

The cost-effectiveness of dulaglutide versus liraglutide for the treatment of type 2 diabetes mellitus in Spain in patients with BMI ≥30 kg/m2.

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.

Economic analysis of rivaroxaban for the treatment and long-term prevention of venous thromboembolism in Portugal.

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.

Cost-effectiveness of rivaroxaban for stroke prevention in atrial fibrillation in the Portuguese setting.

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.