No abstract

Novel cancer therapies are associated with survival patterns that differ from established therapies, which may include survival curves that plateau after a certain follow-up time point. A fraction of the patient population is then considered statistically cured and subject to the same mortality experience as the cancer-free general population. Mixture cure models have been developed to account for this characteristic. As compared to standard survival analysis, mixture cure models can often lead to profoundly different estimates of long-term survival, required for health economic evaluations. This tutorial is designed as a practical introduction to mixture cure models. Step-by-step instructions are provided for the entire implementation workflow, i.e., from gathering and combining data from different sources to fitting models using maximum likelihood estimation and model results interpretation. Two mixture cure models were developed to illustrate (1) an "uninformed" approach where the cure fraction is estimated from trial data and (2) an “informed” approach where the cure fraction is obtained from an external source (e.g., real-world data) used as an input to the model. These models were implemented in the statistical software R, with the freely available code on GitHub. The cure fraction can be estimated as an output from (“uninformed” approach) or used as an input to (“informed” approach) a mixture cure model. Mixture cure models suggest presumed estimates of long-term survival proportions, especially in instances where some fraction of patients is expected to be statistically cured. While this type of model may initially seem complex, it is straightforward to use and interpret. Mixture cure models have the potential to improve the accuracy of survival estimates for treatments associated with statistical cure, and the present tutorial outlines the interpretation and implementation of mixture cure models in R. This type of model will likely become more widely used in health economic analyses as novel cancer therapies enter the market. Supplementary Information The online version contains supplementary material available at 10.1007/s41669-021-00260-z.

Objectives:The HTA Core Model® was developed to improve the transferability of health technology assessment (HTA) between settings. The model has been used by HTA agencies but is also of interest to manufacturers, for improving internal evidence generation and communicating with other HTA stakeholders. To establish if the model is fit for purpose from an industry perspective, the pharmaceutical company Roche, collaborating with the European Network for HTA (EUnetHTA), conducted an assessment of the model.Methods:A questionnaire was developed to evaluate all assessment elements in the HTA Core Model v2.0 for their usefulness in meeting payers’ evidence needs and demonstrating value. The questionnaire was completed by country affiliate teams working in evidence generation and reimbursement submissions for pharmaceuticals. Survey results were discussed in workshops to ensure consistency and alignment between teams.Results:The questionnaire was completed by six teams. An additional team from global pricing and market access participated in workshops. Model domains pertaining to the health problem and current technology use, technology description, clinical effectiveness, and economic value were considered most important because they meet payers’ evidence needs. Overall, the model was considered useful to improve the efficiency of HTA evidence generation, share evidence internally, and communicate value to payers and HTA agencies.Conclusions:From an industry perspective, the HTA Core Model provides a useful framework and common terminology for efficient generation of transferable HTA evidence. The timeliness, efficiency, and transparency of HTA processes could be improved by a more standardized approach to HTA across settings.

Background: Severe hypoglycemic events (SHEs) in patients with diabetes are associated with substantial health care costs in the United States (US). Injectable glucagon (IG) is currently available for treatment of severe hypoglycemia but is associated with frequent handling errors. Nasal glucagon (NG) is a novel, easier-to-use treatment that is more often administered successfully. The economic impact of this usability advantage was explored in cost-offset and budget impact analyses for the US setting. Methods: A health economic model was developed to estimate mean costs per SHE for which treatment was attempted using NG or IG, which differed only in the probability of treatment success, based on a published usability study. The budget impact of NG was projected over 2 years for patients with type 1 diabetes (T1D) and type 2 diabetes treated with basal-bolus insulin (T2D-BB). Epidemiologic and cost data were sourced from the literature and/or fee schedules. Results: Mean costs were $992 lower if NG was used compared with IG per SHE for which a user attempted treatment. NG was estimated to reduce SHE-related spending by $1.1 million and $230 000 over 2 years in 10 000 patients each with T1D and T2D-BB, respectively. Reduced spending resulted from reduced professional emergency services utilization as successful treatment was more likely with NG. Conclusions: The usability advantage of NG over IG was projected to reduce SHE-related treatment costs in the US setting. NG has the potential to improve hypoglycemia emergency care and reduce SHE-related treatment costs.

Introduction Glucagon-like peptide-1 (GLP-1) receptor agonists are used successfully in the treatment of patients with type 2 diabetes as they are associated with low hypoglycemia rates, weight loss and improved glycemic control. This study compared, in the Spanish setting, the cost-effectiveness of liraglutide 1.8 mg versus lixisenatide 20 μg, both GLP-1 receptor agonists, for patients with type 2 diabetes who had not achieved glycemic control targets on metformin monotherapy.MethodsThe IMS CORE Diabetes Model was used to project clinical outcomes and costs, expressed in 2015 Euros, over patient lifetimes. Baseline cohort data and treatment effects were taken from the 26-week, open-label LIRA-LIXI™ trial (NCT01973231). Treatment and management costs of diabetes-related complications were retrieved from published sources and databases. Future benefits and costs were discounted by 3% annually. Sensitivity analyses were conducted.ResultsCompared with lixisenatide 20 μg, liraglutide 1.8 mg was associated with higher life expectancy (14.42 vs. 14.29 years), higher quality-adjusted life expectancy [9.40 versus 9.26 quality-adjusted life years (QALYs)] and a reduced incidence of diabetes-related complications. Higher acquisition costs resulted in higher total costs for liraglutide 1.8 mg (EUR 42,689) than for lixisenatide 20 μg (EUR 42,143), but these were partly offset by reduced costs of treating diabetes-related complications (EUR 29,613 vs. EUR 30,636). Projected clinical outcomes and costs resulted in an incremental cost-effectiveness ratio of EUR 4113 per QALY gained for liraglutide 1.8 mg versus lixisenatide 20 μg.ConclusionsLong-term projections in the Spanish setting suggest that liraglutide 1.8 mg is likely to be cost-effective compared with lixisenatide 20 μg in type 2 diabetes patients who have not achieved glycemic control targets on metformin monotherapy. Liraglutide 1.8 mg presents a clinically and economically attractive treatment option in the Spanish setting.

Purpose Physical activity has been shown to improve survival and quality of life of cancer patients. Due to differences in patient populations, healthcare settings, and types of intervention, cost-effectiveness analyses of physical activity interventions in cancer survivors are difficult to compare. Available evidence from breast cancer survivor research has shown inconsistent results, and transfer of results to other types of cancer is not straightforward. This paper systematically reviewed current evidence on the cost-effectiveness of physical activity interventions in cancer survivors independent of cancer type compared to usual care or another experimental intervention. Methods The literature search was conducted in seven databases and enhanced by a search for gray literature. Eligible studies were restricted to developed countries and assessed using the CHEERS, CHEC, and PHILIPS checklists. The study protocol was pre-published in PROSPERO. Results Seven studies, five cost-utility, and two combined cost-utility/cost-effectiveness analyses fully met the inclusion criteria. They covered eight different types of cancer and various interventions. The cost-effectiveness analyses were of moderate to high methodological quality. A high probability of cost-effectiveness was reported in two analyses. One intervention appeared to be not cost-effective, and one to be cost-effective only from an organizational perspective. Three other analyses reported a cost-effectiveness better than US$ 101,195 (€ 80,000) per QALY gained. Conclusions Physical activity interventions in cancer survivors of developed countries were cost-effective in some but not all clinical trials reviewed. Implications for Cancer Survivors Cost-effectiveness of physical activity interventions appear to depend upon the intensity of the activity.

Introduction Few patients with type 2 diabetes mellitus (T2DM) achieve recommended glycemic control targets in the Czech Republic. Novel therapies, such as fixed-ratio combinations of basal insulin plus glucagon-like peptide-1 receptor agonists, may contribute to better glycemic control. In the analysis presented here, the present analysis assessed the long-term cost-effectiveness of two fixed-ratio combinations, IDegLira (insulin degludec/liraglutide) and iGlarLixi (insulin glargine/lixisenatide), for the treatment of patients with T2DM inadequately controlled with basal insulin from a healthcare payer perspective in the Czech Republic. Methods A cost-effectiveness analysis was performed over patient lifetimes using the IQVIA CORE Diabetes Model. Treatment effects were obtained from an indirect treatment comparison as no head-to-head data for IDegLira versus iGlarLixi are currently available. IDegLira was compared with two iGlarLixi pens (100 U/mL insulin glargine + 33 μg/mL and 50 μg/mL of lixisenatide, respectively). Direct medical costs associated with pharmaceutical interventions, screening and diabetes-related complications were captured. Deterministic and probabilistic sensitivity analyses were performed. Results IDegLira was associated with gains in life expectancy of 0.11 years and in quality-adjusted life expectancy of 0.14 quality-adjusted life-years (QALYs) versus iGlarLixi, due to a lower cumulative incidence and delayed onset of diabetes-related complications. IDegLira was also associated with higher projected costs due to higher acquisition costs; however, these were partially offset by cost savings from avoided complications. IDegLira was associated with incremental cost-effectiveness ratios of Czech Koruna (CZK) 695,998 and CZK 348,323 per QALY gained versus iGlarLixi pens containing 33 and 50 μg/mL of lixisenatide, respectively. These ratios were below the commonly used willingness-to-pay threshold of CZK 1,200,000 per QALY gained. Conclusion The present analysis indicated that IDegLira was associated with clinical benefits relative to iGlarLixi over patient lifetimes and was likely to be cost-effective in the treatment of patients with T2DM uncontrolled on basal insulin in the Czech Republic. Funding Novo Nordisk. Plain Language Summary Plain language summary is available for this article. Electronic Supplementary Material The online version of this article (10.1007/s13300-019-0569-7) contains supplementary material, which is available to authorized users.

ObjectiveItalian treatment guidelines for type 2 diabetes mellitus (T2DM) target good glycemic control but acknowledge the associated risk of hypoglycemia. Unlike traditional antidiabetic therapies, modern treatment options such as fixed-ratio combinations of basal insulin and glucagon-like peptide 1 receptor agonists are associated with improved glycemic control, reduced body weight and low risk of hypoglycemia. The cost-effectiveness of the fixed-ratio combinations of basal insulin and glucagon-like peptide 1 receptor agonists IDegLira and iGlarLixi was assessed for Italy in patients with T2DM uncontrolled on basal insulin, to evaluate how short-term clinical benefits translate into long-term health economic outcomes.MethodsThe IQVIA CORE Diabetes Model was used to project clinical and economic outcomes over patient lifetimes. Treatment effects were sourced from an indirect treatment comparison. The analysis captured direct medical costs (expressed in 2017 Euros) from the perspective of the Italian National Health Service (NHS) and patient-related quality of life. Sensitivity analyses were performed.ResultsIDegLira was associated with gains of 0.09 life years and 0.13 quality-adjusted life years (QALYs) relative to iGlarLixi, due to a lower cumulative incidence and delayed onset of diabetes-related complications. IDegLira was associated with an incremental cost of EUR 930 over patient lifetimes, leading to an incremental cost-effectiveness ratio of EUR 7,386 per QALY gained.ConclusionOver the lifetime of patients with T2DM uncontrolled on basal insulin, IDegLira was associated with improved clinical outcomes at higher costs relative to iGlarLixi. At a willingness-to-pay threshold of EUR 30,000 per QALY gained, IDegLira was considered to be cost-effective versus iGlarLixi from the perspective of the Italian NHS.