Examining the Impact of Structural Uncertainty Across 10 Type 2 Diabetes Models: Results From the 2022 Mount Hood Challenge.

OBJECTIVES: The Mount Hood Diabetes Challenge Network aimed to examine the impact of model structural uncertainty on the estimated cost-effectiveness of interventions for type 2 diabetes. METHODS: Ten independent modeling groups completed a blinded simulation exercise to estimate the cost-effectiveness of 3 interventions in 2 type 2 diabetes populations. Modeling groups were provided with a common baseline population, cost and utility values associated with different model health states, and instructions regarding time horizon and discounting. We collated the results to identify variation in predictions of net monetary benefit (NMB) and the drivers of those differences. RESULTS: Overall, modeling groups agreed which interventions had a positive NMB (ie, were cost-effective), Although estimates of NMB varied substantially-by up to £23 696 for 1 intervention. Variation was mainly driven through differences in risk equations for complications of diabetes and their implementation between models. The number of modeled health states was also a significant predictor of NMB. CONCLUSIONS: This exercise demonstrates that structural uncertainty between different health economic models affects cost-effectiveness estimates. Although it is reassuring that a decision maker would likely reach similar conclusions on which interventions were cost-effective using most models, the range in numerical estimates generated across different models would nevertheless be important for price-setting negotiations with intervention developers. Minimizing the impact of structural uncertainty on healthcare decision making therefore remains an important priority. Model registries, which record and compare the impact of structural assumptions, offer one potential avenue to improve confidence in the robustness of health economic modeling.

MRI-only radiotherapy from an economic perspective: Can new techniques in prostate cancer treatment be cost saving?

Background and Purpose: The aim of this study was to analyze a magnetic resonance imaging (MRI)-only radiotherapy workflow from an economic perspective in terms of reduced time, costs and systematic uncertainties. Material/Methods: A documented Swedish clinical implementation of MRI-only radiotherapy was used as template for cost assessments compared to a combined computed tomography (CT)/MRI workflow. The costs were taken from official regional price lists from 2021. MRI-only specific quality assurance (QA) was assumed necessary in an initial phase. Treatment plans for target volumes with margins of 5-10 mm were created for ten prostate cancer patients prescribed 78 Gy in 39 fractions. The risk of Grade ≥ 2 rectal toxicity or rectal bleeding was calculated using the QUANTEC recommended NTCP model and costs estimated based on subsequent diagnostic examinations. Results: The exclusion of the CT-examination and faster target delineation were the main contributors to cost reductions. Additional QA procedures limited the initial cost reduction to 14 EUR/patient. Long-term MRI-only reduced the costs by 209 EUR/patient. Reducing margins resulted in Grade ≥ 2 rectal toxicity or rectal bleeding probability of 9.7 % for 7 mm margin and 6.0 % for 5 mm margin. This margin reduction resulted in an additional cost reduction of 46 EUR/patient. Conclusion: An MRI-only workflow implementation is associated with reduced costs when the workflow tasks are more time efficient and side effects are reduced as a result of margin reduction. The short-term economic benefits are limited due to extra costs of QA procedures. The economic benefits of MRI-only will make impact first when the workflow is well established, and margin reduction has been included.

The implementation of a noninvasive lymph node staging (NILS) preoperative prediction model is cost effective in primary breast cancer.

PURPOSE: The need for sentinel lymph node biopsy (SLNB) in clinically node-negative (cN0) patients is currently questioned. Our objective was to investigate the cost-effectiveness of a preoperative noninvasive lymph node staging (NILS) model (an artificial neural network model) for predicting pathological nodal status in patients with cN0 breast cancer (BC). METHODS: A health-economic decision-analytic model was developed to evaluate the utility of the NILS model in reducing the proportion of cN0 patients with low predicted risk undergoing SLNB. The model used information from a national registry and published studies, and three sensitivity/specificity scenarios of the NILS model were evaluated. Subgroup analysis explored the outcomes of breast-conserving surgery (BCS) or mastectomy. The results are presented as cost (€) and quality-adjusted life years (QALYs) per 1000 patients. RESULTS: All three scenarios of the NILS model reduced total costs (-€93,244 to -€398,941 per 1000 patients). The overall health benefit allowing for the impact of SLNB complications was a net health gain (7.0-26.9 QALYs per 1000 patients). Sensitivity analyses disregarding reduced quality of life from lymphedema showed a small loss in total health benefits (0.4-4.0 QALYs per 1000 patients) because of the reduction in total life years (0.6-6.5 life years per 1000 patients) after reduced adjuvant treatment. Subgroup analyses showed greater cost reductions and QALY gains in patients undergoing BCS. CONCLUSION: Implementing the NILS model to identify patients with low risk for nodal metastases was associated with substantial cost reductions and likely overall health gains, especially in patients undergoing BCS.

Cost-Effectiveness of Once-Weekly Semaglutide 1 mg versus Canagliflozin 300 mg in Patients with Type 2 Diabetes Mellitus in a Canadian Setting.

OBJECTIVE: Our objective was to evaluate the long-term cost-effectiveness of once-weekly semaglutide 1 mg versus once-daily canagliflozin 300 mg in patients with type 2 diabetes mellitus (T2DM) uncontrolled with metformin from the healthcare payer and societal perspectives in Canada. METHODS: Head-to-head data from the SUSTAIN 8 randomised trial (NCT03136484) were extrapolated over 40 years using economic simulation modelling. The cost-effectiveness of once-weekly semaglutide 1 mg versus canagliflozin 300 mg for treating T2DM was estimated using the Swedish Institute for Health Economics-Diabetes Cohort Model (IHE-DCM) and the Economic and Health Outcomes Model of T2DM (ECHO-T2DM). Unit costs and disutility weights capturing treatments and key macro- and microvascular complications were sourced from the literature to best match the Canadian setting. A probabilistic base-case simulation and sensitivity analyses were conducted. RESULTS: Once-weekly semaglutide 1 mg was associated with reductions in macro- and microvascular complications, yielding incremental cost-effectiveness ratios (ICERs) of (Canadian dollars [CAD]) CAD16,392 and 18,098 per incremental quality-adjusted life-year (QALY) gained versus canagliflozin 300 mg for IHE-DCM and ECHO-T2DM, respectively, from a healthcare payer perspective. Accounting for productivity loss as well, ICERs were CAD14,127 and 13,188 per QALY gained for IHE-DCM and ECHO-T2DM, respectively, from a societal perspective. Sensitivity analyses confirmed that the base-case results were robust to changes in input parameters and assumptions used. CONCLUSIONS: At a willingness-to-pay threshold of CAD50,000 per QALY gained, once-weekly semaglutide 1 mg was cost-effective over 40 years versus once-daily canagliflozin 300 mg for the treatment of T2DM in patients failing to maintain glycemic control with metformin alone.

Long-Term Cost Effectiveness of Oral Semaglutide Versus Empagliflozin and Sitagliptin for the Treatment of Type 2 Diabetes in the Swedish Setting.

OBJECTIVE: The aim of this study was to assess the cost effectiveness of oral semaglutide versus other oral glucose-lowering drugs for the management of type 2 diabetes (T2D) in Sweden. METHODS: The Swedish Institute for Health Economics Diabetes Cohort Model was used to assess the cost effectiveness of oral semaglutide 14 mg versus empagliflozin 25 mg and oral semaglutide 14 mg versus sitagliptin 100 mg, using data from the head-to-head PIONEER 2 and 3 trials, respectively, in which these treatments were added to metformin (± sulphonylurea). Base-case and scenario analyses were conducted. Robustness was evaluated with deterministic and probabilistic sensitivity analyses. RESULTS: In the base-case analyses, greater initial lowering of glycated haemoglobin levels with oral semaglutide versus empagliflozin and oral semaglutide versus sitagliptin, respectively, resulted in reduced incidences of micro- and macrovascular complications and was associated with lower costs of complications and indirect costs. Treatment costs were higher for oral semaglutide, resulting in higher total lifetime costs than with empagliflozin (Swedish Krona [SEK] 1,245,570 vs. 1,210,172) and sitagliptin (SEK1,405,789 vs. 1,377,381). Oral semaglutide was shown to be cost effective, with an incremental cost-effectiveness ratio (ICER) of SEK239,001 per quality-adjusted life-year (QALY) compared with empagliflozin and SEK120,848 per QALY compared with sitagliptin, from a payer perspective. ICERs were lower at SEK191,721 per QALY compared with empagliflozin and SEK95,234 per QALY compared with sitagliptin from a societal perspective. Results were similar in scenario analyses that incorporated cardiovascular effects, and also in sensitivity analyses. CONCLUSIONS: In a Swedish setting, oral semaglutide was cost effective compared with empagliflozin and sitagliptin for patients with T2D inadequately controlled on oral glucose-lowering drugs. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02863328 (PIONEER 2; registered 11 August 2016) and NCT02607865 (PIONEER 3; registered 18 November 2015).

For any disease, it is important to consider whether new treatments, which may be more effective but also more expensive, are worth paying for compared with treatments that are already being used. This is called a cost-effectiveness analysis and helps health authorities and other organisations (such as insurance companies) that pay for medications to decide whether or not to pay for the new treatment. Cost effectiveness differs between individual countries because each has its own health system, health costs and approved treatments. Semaglutide is a type of medication called a glucagon-like peptide-1 receptor agonist (or GLP-1RA) that is used by people with type 2 diabetes to help control their blood glucose (sugar). Semaglutide is administered by injection but has recently become the first GLP-1RA to be available in a once-daily oral (tablet) form. We used information from the Swedish Institute for Health Economics and two clinical trials of oral semaglutide that compared it with other oral glucose-lowering drugs­empagliflozin and sitagliptin­to work out whether oral semaglutide was a cost-effective treatment in Sweden. We found that oral semaglutide was more expensive than empagliflozin and sitagliptin over the entire time on treatment but also led to greater lowering of blood sugar. This means that patients had fewer other illnesses linked to diabetes and lower health costs as a result. Balancing the higher upfront cost of the drug versus savings from fewer illnesses linked to diabetes, we found that in Sweden, oral semaglutide was cost effective compared with empagliflozin and sitagliptin.

The Value of a New Diagnostic Test for Prostate Cancer: A Cost-Utility Analysis in Early Stage of Development.

BACKGROUND: Standard biopsy for prostate cancer diagnosis is an unpleasant and sometimes painful procedure with a detection rate as low as around 50%. Consequently, an accurate blood-based test would be highly desirable to improve the predictive accuracy. However, the clinical value of a new blood test for diagnosing prostate cancer depends on its sensitivity and specificity, in relation to the selected target population. OBJECTIVE: The aim of this analysis was to investigate the health-economic value of introducing a new and more accurate diagnostic blood-based test to identify men in need of a biopsy to diagnose prostate cancer. METHOD: We developed a Discrete Event Simulation Model with outputs including number of biopsies, cancer diagnosis, treatments and prostate cancer deaths. The analysis was performed from a health care perspective. It used epidemiologic data, treatment patterns, and health care costs from the Swedish region Skåne (population of 1.3 million). A 90% sensitivity and specificity of the new test was assumed. RESULTS: Among 31,250 men, age 50-69 years, 16.4% had a PSA between 3.0 and 9.9 µg/L and 28.9% a PSA of 2.0-9.9 µg/L. Testing men with PSA 3.0-9.9 µg/L, as in current clinical practice, decreased the number of biopsies by 3595, detected 61 more cancers, resulting in and two more fatalities and subsequently a loss of 14 QALYs. Cost offsets could justify a test value of SEK 4996. Testing a larger population, PSA 2.0-9.9 µg/L prevented 6 deaths, added 50 QALYs, and could justify a value of the test of SEK 5165, given a value of health of SEK 500,000 per QALY. CONCLUSION: A new blood-based test for prostate cancer has a significant potential to reduce the number of biopsies needed, resulting in reduced health care costs and improve patient care.

Comparing the Cohort and Micro-Simulation Modeling Approaches in Cost-Effectiveness Modeling of Type 2 Diabetes Mellitus: A Case Study of the IHE Diabetes Cohort Model and the Economics and Health Outcomes Model of T2DM.

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.

Cost-effectiveness of once-weekly semaglutide versus dulaglutide and lixisenatide in patients with type 2 diabetes with inadequate glycemic control in Sweden.

Aims: This analysis evaluated the cost-effectiveness of once-weekly semaglutide vs glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes (T2D) uncontrolled on metformin or basal insulin in Sweden. Materials and methods: This cost-effectiveness analysis (CEA) was conducted using the Swedish Institute of Health Economics (IHE) Diabetes Cohort Model. Analyses were conducted from the Swedish societal perspective over a time horizon of 40 years. For patients uncontrolled on metformin, dulaglutide was the comparator, and data from the SUSTAIN 7 clinical trial was used. For patients uncontrolled on basal insulin, lixisenatide was chosen as the comparator and data was obtained from a network meta-analysis (NMA). Results: The results show that, in patients with inadequate control on metformin, semaglutide 1.0 mg dominated (i.e. provided greater clinical benefit, and was less costly) dulaglutide 1.5 mg. In patients with inadequate control on basal insulin, semaglutide 1.0 mg dominated lixisenatide. The reduction in costs is largely driven by the reduction in complications seen with once-weekly semaglutide. Limitations and conclusions: It is likely that this analysis is conservative in estimating the cardiovascular (CV) cost benefits associated with treatment with once-weekly semaglutide. In patients inadequately controlled on basal insulin, the analyses vs lixisenatide were based on results from an NMA, as no head-to-head clinical trial has been conducted for this comparison. These CEA results show that once-weekly semaglutide is a cost-effective GLP-1 RA therapy for the treatment of T2D in patients inadequately controlled on metformin or basal insulin, addressing many current clinician, patient, and payer unmet needs in Sweden.

Intraductal papillary mucinous neoplasms of the pancreas - a cost-effectiveness analysis of management strategies for the branch-duct subtype.

BACKGROUND: Branch-duct intraductal papillary mucinous neoplasm (BD-IPMN) presents a clinical conundrum. Rigorous long-term surveillance or surgical resection is recommended. The economic consequences of the management have not been fully investigated. METHODS: A Markov decision model compared 4 strategies for low-risk BD-IPMN: I = upfront total pancreatectomy, II = upfront partial pancreatectomy, III = initial surveillance, IV = watchful waiting. Surveillance was based on the Swedish Guidelines for Pancreatic Cancer. Probabilities and costs were obtained from the participating unit and from the scientific literature. The incremental cost-effectiveness ratios (ICERs) were calculated and sensitivity analyses were performed by varying relevant parameters. Survival was reported in quality-adjusted life-years (QALYs). RESULTS: Strategy III was the most cost-effective strategy with an ICER of €31 682 compared to strategy IV. Strategy I was the most expensive but yielded the best QALY (9.32). Total number of years, annual risk of pancreatic cancer and annual risk of a low-risk BD-IPMN turning into a high-risk lesion had the greatest impact in the model. CONCLUSIONS: Initial surveillance seems to be the most cost-effective strategy in the management of low-risk asymptomatic BD-IPMN. However, the possibility of personalized approaches remains to be investigated.

Cost-effectiveness of liraglutide versus lixisenatide as add-on therapies to basal insulin in type 2 diabetes.

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.