De Novo Cost-Effectiveness Model Framework for Nonalcoholic Steatohepatitis-Modeling Approach and Validation.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a chronic liver disease associated with hepatic morbidity and mortality and extra-hepatic comorbidities. Published NASH cost-effectiveness models (CEMs) are heterogeneous and consistently omit comorbid conditions that frequently co-exist alongside NASH. We aimed to develop a de novo CEM framework that incorporates extra-hepatic disease states and outcomes alongside hepatic components to enable future estimation of the cost-effectiveness of NASH interventions. METHODS: Patient-level simulation and cohort-level Markov models were implemented in the same framework. Model inputs included fibrosis progression; late-stage liver disease outcomes; comorbidity outcomes for cardiovascular disease, type 2 diabetes, and obesity; mortality; health-related quality of life; and direct medical costs. The prototype analysis assessed the cost-effectiveness of obeticholic acid versus standard of care from a US payer perspective over a lifetime horizon with costs and effects discounted at 3% per annum. However, the CEM was designed for easy adaptation to other countries, time horizons, and other considerations. Efficacy and adverse event parameters were obtained from the 18-month interim analysis of the REGENERATE trial. Outputs include total and incremental costs, total life years, and quality-adjusted life years. RESULTS: In this model, total costs, total life years, and quality-adjusted life years were all higher with obeticholic acid compared with standard of care. Cross-validation of this model with the 2016 and 2020 Institute for Clinical and Economic Review models revealed marked differences, mainly driven by mortality inputs, transition probability estimates, and incorporation of the effect of treatment and comorbidities. CONCLUSION: This is the first CEM in NASH to incorporate the clinical consequences of several comorbidities. The flexible yet standardized framework permits estimation of the cost-effectiveness of NASH interventions in a variety of settings. The model currently includes several assumptions and will be further developed as more relevant data become available.

Once-Weekly Subcutaneous Semaglutide 2.4 mg Injection is Cost-Effective for Weight Management in the United Kingdom.

OBJECTIVES: The objective of the current preliminary study was to present the cost-effectiveness analyses submitted to the National Institute for Health and Care Excellence (NICE) (TA10765) that deemed semaglutide 2.4 mg subcutaneous (s.c.) injection a cost-effective option for weight management in the United Kingdom (UK) alongside diet and exercise (D&E). METHODS: The study was conducted from the National Health Service (NHS) and Personal Social Services perspective and based on the NICE reference case. The clinical safety and efficacy of semaglutide 2.4 mg s.c. injection were obtained from the Semaglutide Treatment Effect in People with Obesity (STEP) 1 trial. The previously published and validated Core Obesity Model was used to project lifetime occurrence of obesity complications, their costs and quality of life consequences over 40 years. The base case cohort had a mean starting age of 48 years and BMI of 38.7 kg/m2. The confidential NHS price for semaglutide 2.4 mg s.c. injection was provided by Novo Nordisk. The incremental cost-effectiveness ratios (ICERs) were expressed as cost/quality-adjusted life-year (QALY). Uncertainty was assessed through sensitivity analyses, including a scenario analysis using clinical data from the STEP 2 trial and a previously published and validated Core Diabetes Model to investigate a cohort with type 2 diabetes at baseline. RESULTS: Semaglutide 2.4 mg s.c. injection showed higher total costs and health benefits compared with D&E, with an ICER of £14,827/QALY gained. The probabilistic sensitivity analysis showed that semaglutide 2.4 mg s.c. injection was cost-effective in 90% of cases at a willingness-to-pay threshold of £20,000/QALY. The ICER from the scenario analysis for the diabetic population was £16,613/QALY gained, using the Core Diabetes Model. CONCLUSION: Semaglutide 2.4 mg s.c. injection is a cost-effective therapy compared to D&E alone for patients with obesity and weight-related comorbidities in the UK. Sensitivity and scenario analyses confirm the robustness of the analyses.

Semaglutide 2.4 Mg for the Management of Overweight and Obesity: Systematic Literature Review and Meta-Analysis.

Purpose: Semaglutide has demonstrated safe and effective weight loss for overweight and obesity, including participants with concomitant type 2 diabetes mellitus (T2DM), in randomized placebo-controlled trials (RCTs). We conducted a systematic literature review (SLR) and network meta-analyses (NMA) to compare weekly semaglutide 2.4 mg with pharmacological comparators for weight management in overweight or obesity. Methods: The SLR was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist. NMAs were performed to compare weight change for semaglutide 2.4 mg with comparators using data identified in the SLR. The populations of interest were total population, normal glucose tolerance, non-T2DM, pre-diabetes, and T2DM. Included outcomes were weight change from baseline (CFB, %) at 52 weeks and proportion of participants losing ≥5% baseline fasting body weight at 12 weeks (at full therapeutic dose). Results: The SLR identified 108 RCTs examining non-surgical interventions, of which 41 were considered for inclusion in the NMAs. In all populations, semaglutide 2.4 mg was associated with a greater percentage weight CFB with 52 weeks of treatment versus all available comparators. In all populations, semaglutide was associated with a higher likelihood of participants losing ≥5% of baseline fasting body weight at 12 weeks versus all available comparators. Conclusion: In NMA, semaglutide 2.4 mg demonstrated effective weight loss (≥5%) in the total population and all subpopulations of glucose tolerance versus active comparators. Semaglutide is an effective treatment that may address unmet need in the management of overweight and obesity.

An economic assessment of analogue basal-bolus insulin versus human basal-bolus insulin in subjects with type 1 diabetes in the UK.

BACKGROUND: A recent study demonstrated that treatment of type 1 diabetes with an analogue basal-bolus insulin regimen was associated with improved glycaemic control (HbA(1c) -0.22% points, p < 0.001), reduced risk of hypoglycaemic events (-21%, p = 0.036) and reduction in body mass index (-0.30 kg/m(2), p < 0.001) compared to a human basal-bolus regimen after 18 weeks. METHODS: A published and validated computer simulation model was used to project long-term economic and clinical outcomes in a simulated cohort of type 1 diabetes patients treated with either insulin detemir plus insulin aspart (analogue) or Neutral Protamine Hagedorn plus human soluble insulin (human), in a UK setting. Probabilities of complications and HbA(1c)-dependent adjustments were derived from major clinical and epidemiological studies. Complication and treatment costs were projected over patient lifetimes from a National Health Service perspective. Costs and clinical benefits were discounted at 3.5% annually. RESULTS: Quality-adjusted life expectancy (QALE) was 0.66 quality-adjusted life years (QALY) higher in the analogue insulin versus the human insulin group (mean +/- SD) (7.65 +/- 0.09 versus 6.99 +/- 0.08). Direct lifetime costs were 1654 pounds greater with analogue versus human insulin treatment (40,876 pounds +/- 1119 versus 39,222 pounds+/- 1141), producing an incremental cost effectiveness ratio (ICER) of 2500 pounds per QALY gained. Sensitivity analyses showed the results were robust under a range of plausible scenarios. CONCLUSIONS: Treatment with analogue insulin was associated with a decreased incidence of long-term complications and improved QALE, but slightly higher treatment costs compared to human insulin therapy. Analogue insulin treatment had an ICER within the range generally considered to represent good value for money in the UK.

Cost-effectiveness of detemir-based basal/bolus therapy versus NPH-based basal/bolus therapy for type 1 diabetes in a UK setting: an economic analysis based on meta-analysis results of four clinical trials.

BACKGROUND: A meta-analysis of results from four clinical trials in type 1 diabetes patients showed that insulin detemir (IDet)-based basal/bolus treatment of type 1 diabetes led to improved HbA1c (0.15%-points lower), reduced risk of major hypoglycaemic events (by 2%) and reduction in body mass index (BMI) (0.26 kg/m2) compared to protamine Hagedorn human (NPH) insulin-based basal/bolus therapy in type 1 patients. METHODS: A published, validated, peer-reviewed Markov simulation model (the CORE Diabetes Model) projected short-term results obtained from the fixed-effects (weighted average) meta-analysis to long-term incidence of complications, improvements in quality-adjusted life years (QALY), long-term costs and the cost-effectiveness for IDet combinations versus NPH combinations in type 1 diabetes patients. Probabilities of complications and HbA1c-dependent adjustments were derived from the DCCT and other studies. Costs of treating complications in the UK were retrieved from published sources. Total direct costs (complications + treatment costs) for each arm were projected over patient lifetimes from a UK National Heath Service perspective. Both costs and clinical outcomes were discounted at 3.5% annually. RESULTS: Improved glycaemic control, decreased hypoglycaemic events and BMI with IDet-based basal/bolus therapy led to fewer diabetes-related complications, an increase in quality-adjusted life expectancy of 0.09 years, increased total lifetime costs/patient of 1707 pounds sterling and an incremental cost-effectiveness ratio of 19,285 pounds sterling per QALY gained. Results were stable under a wide range of reasonable assumptions. CONCLUSIONS: Short-term improvements seen with IDet combinations versus NPH combinations led to decreased complications, improvements in QALYs and reductions in complication costs, which partially offset the additional costs of detemir, leading to a cost-effectiveness ratio which fell within a range considered to represent excellent value for money (< 35,000 pounds sterling/QALY gained).