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This article discusses the challenges of conducting head-to-head clinical trials for evaluating the efficacy of treatments for haemophilia A, a rare lifelong condition. The standard-of-care for haemophilia A is prophylaxis with recombinant FVIII replacement therapy. Since head-to-head trials for all available FVIII products have not been conducted, indirect approaches have been proposed to compare these products. The article presents an updated analysis using a decision analytical model to compare FVIII products based on the area under the plasma level curve (AUC). The results show that extended half-life (EHL) products have a larger AUC compared to standard half-life (SHL) products. However, further investigation is needed to understand the clinical implications of these findings. [Extracted from the article]

Background: Economic modeling is widely used in estimating cost-effectiveness in type 2 diabetes mellitus. Because type 2 diabetes is complex and patients are heterogenous, the cohort modeling approach may generate biased estimates of costeffectiveness. The IHE Diabetes Cohort Model (IHE-DCM) was constructed using the cohort approach as an alternative for stakeholders with limited resources, some of whom have voiced reasonable concerns about a lack of transparency with type 2 diabetes micro-simulation models and long run times. Objectives: The objective of this study was to inform decision makers by investigating the direction and magnitude of bias of IHE-DCM cost-effectiveness estimates that can be attributed to the cohort modeling approach. Methods: Simulation scenarios inspired by the 9th Mount Hood Diabetes Challenge were simulated with IHE-DCM and with a micro-simulation model, the Economic and Health Outcomes Model of T2DM (ECHO-T2DM), and key metrics (absolute and incremental costs and quality-adjusted life-years, event rates, and cost-effectiveness) were compared for evidence of systematic differences. The models were harmonized to the extent possible to ensure that differences were driven primarily by the unit of observation and not by other model differences. Results: IHE-DCM run times were faster and IHE-DCM produced uniformly larger estimates of absolute life-years, quality-adjusted life-years, and costs than ECHO-T2DM but smaller between-arm (incremental) differences. Estimated incremental cost-effectiveness ratios and net monetary benefits varied similarly and predictably across the scenarios. On average, IHE-DCM estimates of incremental cost-effectiveness ratios and net monetary benefits were CAN$269 (3%) and CAN$2935 (10%) smaller, respectively, than ECHO-T2DM. Conclusions: There was little evidence that estimated cost-effectiveness metrics, the outcomes that matter most to stakeholders, differed systematically. [ABSTRACT FROM AUTHOR]

Background: We assessed the cost-effectiveness of the glucagon-like peptide 1 receptor agonists liraglutide 1.8 mg and lixisenatide 20 μg (both added to basal insulin) in patients with type 2 diabetes (T2D) in Sweden. Methods: The Swedish Institute for Health Economics cohort model for T2D was used to compare liraglutide and lixisenatide (both added to basal insulin), with a societal perspective and with comparative treatment effects derived by indirect treatment comparison (ITC). Drug prices were 2016 values, and all other costs 2015 values. The cost-effectiveness of IDegLira (fixed-ratio combination of insulin degludec and liraglutide) versus lixisenatide plus basal insulin was also assessed, under different sets of assumptions. Results: From the ITC, decreases in HbA1c were –1.32% and –0.43% with liraglutide and lixisenatide, respectively; decreases in BMI were –1.29 and –0.65 kg/m2, respectively. An estimated 2348 cases of retinopathy, 265 of neuropathy and 991 of nephropathy would be avoided with liraglutide compared with lixisenatide in a cohort of 10,000 patients aged over 40 years. In the base-case analysis, total direct costs were higher with liraglutide than lixisenatide, but costs associated with complications were lower. The cost/quality-adjusted life-year (QALY) for liraglutide added to basal insulin was SEK30,802. Base-case findings were robust in sensitivity analyses, except when glycated haemoglobin (HbA1c) differences for liraglutide added to basal insulin were abolished, suggesting these benefits were driving the cost/QALY. With liraglutide 1.2 mg instead of liraglutide 1.8 mg (adjusted for efficacy and cost), liraglutide added to basal insulin was dominant over lixisenatide 20μg.IDegLira was dominant versus lixisenatide plus basal insulin when a defined daily dose was used in the model. Conclusions: The costs/QALY for liraglutide, 1.8 or 1.2 mg, added to basal insulin, and for IDegLira (all compared with lixisenatide 20 μg added to basal insulin) were below the threshold considered low by Swedish authorities. In some scenarios, liraglutide and IDegLira were cost-saving. [ABSTRACT FROM AUTHOR]

Background: A1C lowering was significantly greater for oral semaglutide 14 mg than empagliflozin 25 mg for patients with type 2 diabetes mellitus (T2DM) uncontrolled on metformin in the 52-week, randomized, open-label PIONEER 2 trial (NCT02863328). We estimated the cost effectiveness of oral semaglutide vs. empagliflozin in Canada from the payer and societal perspectives. Methods: Modeling methods were used to extrapolate benefits observed in PIONEER 2 to long-term costs and outcomes, including quality-adjusted life-years (QALYs), for patients treated with oral semaglutide or empagliflozin. As with analysis in other settings, the IHE-Diabetes Cohort Model (IHE-DCM) was used. The analysis was also run using the Economic and Health Outcomes microsimulation model (ECHO-T2DM). Patient baseline characteristics and treatment effects were sourced from PIONEER 2. In the model simulations, both agents were assumed discontinued and insulin initiated when A1C was >8.0%. Unit costs (CAD$) and utilities were sourced from the literature. Results: Oral semaglutide was associated with more QALYs than empagliflozin over 40 years (0.39 with IHE-DCM and 0.34 with ECHO-T2DM). The gains came with increased costs (CAD$8,202 with IHE-DCM and CAD$9,255 with ECHO-T2DM), yielding incremental cost-effectiveness ratios (ICERs) of CAD$21,115 and CAD$27,496/QALY gained, respectively, below the often-cited willingness-to-pay threshold of CAD$50,000/QALY. When productivity costs and the full societal perspective are considered, the ICERs were CAD$18,239 and CAD$19,112, respectively. Sensitivity analyses that included cost, treatment effect, time horizon and biomarker rebound assumptions generally confirmed the results. Conclusion: Two models independently found oral semaglutide to be cost-effective compared to empagliflozin over 40 years for the treatment of patients with T2DM uncontrolled on metformin in Canada. While uncommon, the use of two models can reduce decision-making uncertainty. Disclosure: A.R. Liu: Employee; Self; Novo Nordisk Canada Inc. P.G. Bech: Employee; Self; Novo Nordisk Inc. Stock/Shareholder; Self; Novo Nordisk Inc. A. Fridhammar: None. A. Nilsson: None. M. Willis: Board Member; Self; The Swedish Institute for Health Economics. Consultant; Self; Janssen Global Services, LLC., Mundipharma International, Novo Nordisk A/S. Stock/Shareholder; Self; The Swedish Institute for Health Economics. S. Nuhoho: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Johnson & Johnson. Funding: Novo Nordisk Canada Inc. [ABSTRACT FROM AUTHOR]