Lutetium oxodotreotide (177Lu-Dotatate) for the treatment of unresectable or metastatic progressive gastroenteropancreatic neuroendocrine tumors: a cost-effectiveness analysis for Scotland.

BACKGROUND: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) represent a heterogenous group of tumors. Findings from the phase III NETTER-1 trial showed that treatment of unresectable/metastatic progressive gastrointestinal (GI) NETs with 177Lu-Dotatate resulted in a significant improvement in progression-free survival (PFS) and overall survival (OS) compared with best supportive care (BSC) with high dose octreotide long-acting repeatable (LAR) 60 mg. A health economic analysis was performed using input data from clinical studies and data derived from an indirect comparison to determine the cost-effectiveness of 177Lu-Dotatate in the treatment of GI-NETs and pancreatic NETs (P-NETs) in Scotland. METHODS: Cost-effectiveness analysis was performed from the payer perspective using a three-state partitioned survival model. In the base case 177Lu-Dotatate was compared with BSC in gastrointestinal (GI)-NETs using clinical data from the NETTER-1 trial. A secondary analysis comparing 177Lu-Dotatate with BSC, everolimus or sunitinib in patients with P-NETs was also performed using hazard ratios inferred from indirect comparisons. The base case analysis was performed over a 20-year time horizon with an annual discount rate of 3.5% for both costs and clinical outcomes. RESULTS: For unresectable/metastatic progressive GI-NETs treatment with 177Lu-Dotatate led to a gain in quality-adjusted life expectancy of 1.33 quality-adjusted life years (QALYs) compared with BSC due to extended PFS and OS. Mean total lifetime costs were GBP 35,701 higher with 177Lu-Dotatate, leading to an incremental cost-effectiveness ratio (ICER) of GBP 26,830 per QALY gained. In analyses in patients with P-NETs 177Lu-Dotatate was associated with ICERs below GBP 30,000 per QALY gained in comparisons with BSC, sunitinib and everolimus. CONCLUSIONS: Cost-effectiveness analyses demonstrated that, in Scotland, from the payer perspective, 177Lu-Dotatate at the set acquisition cost is a cost-effective treatment option for patients with unresectable or metastatic progressive GI-NETs or P-NETs.

Cost-effectiveness of Lutetium [177Lu] oxodotreotide versus best supportive care with octreotide in patients with midgut neuroendocrine tumors in France.

BACKGROUND AND AIMS: In France, there are approximately 2,400 new cases of neuroendocrine tumors (NETs) annually. Peptide receptor radionuclide therapy with 177Lu-Dotatate plus long-acting repeatable [LAR] octreotide 30 mg has been shown to significantly improve progression-free survival and overall survival relative to high-dose octreotide LAR 60 mg in patients with unresectable or metastatic progressive midgut NETs. A long-term cost-effectiveness analysis was performed to assess whether 177Lu-Dotatate is a cost-effective option versus octreotide 60 mg for patients with unresectable/metastatic progressive midgut NETs from the perspective of French healthcare payer. METHODS: The analysis was performed using a three-state partitioned survival model. In the base case analysis 177Lu-Dotatate plus octreotide LAR 30 mg was compared with high-dose octreotide LAR 60 mg in patients with midgut NETs. Survival data were obtained from the phase III NETTER-1 trial in patients with metastatic midgut NETs. Future costs and clinical outcomes were discounted at 4% per annum. One-way deterministic and probabilistic sensitivity analyses were performed. RESULTS: In the base case analysis, for patients with midgut NETs, 177Lu-Dotatate treatment improved quality-adjusted life expectancy by 1.21 quality-adjusted life years (QALYs) relative to octreotide LAR 60 mg and the lifetime treatment costs were EUR 50,784 higher with 177Lu-Dotatate resulting in an incremental cost-effectiveness ratio (ICER) of EUR 42,106 per QALY gained versus octreotide LAR 60 mg. When compared with everolimus, 177Lu-Dotatate was associated with an ICER of EUR 59,769 per QALY gained. Sensitivity analyses showed that the results were sensitive to methods used to extrapolate survival data. CONCLUSIONS: For patients with advanced progressive midgut NETs 177Lu-Dotatate is likely to be considered a cost-effective option versus octreotide 60 mg from the perspective of the French healthcare payer.

Literature review of the burden of prostate cancer in Germany, France, the United Kingdom and Canada.

BACKGROUND: Prostate cancer is the most frequently reported cancer in males in Europe, and is associated with substantial morbidity and mortality. The aim of the current review was to characterize the clinical, economic and humanistic burden of disease associated with prostate cancer in France, Germany, the UK and Canada. METHODS: Literature searches were conducted using the PubMed, EMBASE and Cochrane Library databases to identify studies reporting incidence and/or mortality rates, costs and health state utilities associated with prostate cancer in the settings of interest. For inclusion, studies were required to be published in English in full-text form from 2006 onwards. RESULTS: Incidence studies showed that in all settings the incidence of prostate cancer has increased substantially over the past two decades, driven in part by increased uptake of prostate specific antigen (PSA) screening leading to earlier identification of tumors, but which has also led to over-treatment, compounding the economic burden of disease. Mortality rates have declined over the same time frame, driven by earlier detection and improvements in treatment. Both prostate cancer itself, as well as treatment and treatment-related complications, are associated with reduced quality of life. CONCLUSIONS: Prostate cancer is associated with a significant clinical and economic burden, whilst earlier detection and aggressive treatment is associated with improved survival, over-treatment of men with indolent tumors compounds the already significant burden of disease and treatment can lead to long-term side effects including impotence and impaired urinary and/or bowel function. There is currently an unmet clinical need for diagnostic and/or prognostic tools that facilitate personalized prostate cancer treatment, and potentially reduce the clinical, economic and humanistic burden of invasive cancer treatment.

Cost-effectiveness of sensor-augmented pump therapy versus standard insulin pump therapy in patients with type 1 diabetes in Denmark.

AIMS: The use of continuous subcutaneous insulin infusion (CSII) in type 1 diabetes (T1D) has increased in recent years. Sensor-augmented pump therapy (SAP) with low glucose suspend (LGS) (allowing temporary suspension of insulin delivery if blood glucose level falls below a pre-defined threshold level) provides additional benefits over CSII alone, but is associated with higher acquisition costs. Therefore, a cost-effectiveness analysis of SAP+LGS versus CSII in patients with T1D was performed. METHODS: Analyses were performed using the CORE Diabetes Model in two different patient cohorts in Denmark, one with hyperglycemia at baseline and one with increased risk for hypoglycemic events. Clinical input data were sourced from published literature. The analysis was performed over a lifetime time horizon from a societal perspective. Future costs and clinical outcomes were discounted at 3% per annum. RESULTS: In patients who were hyperglycemic at baseline the use of SAP+LGS versus CSII resulted in improved quality-adjusted life expectancy (12.44 versus 10.99 quality-adjusted life years [QALYs]) but higher mean lifetime costs (DKK 2,027,316 versus DKK 1,801,293) leading to an incremental cost-effectiveness ratio (ICER) of DKK 156,082 per QALY gained. For patients at increased risk for hypoglycemic events the ICER for SAP+LGS versus CSII was DKK 89,868 per QALY gained. CONCLUSIONS: The ICER for SAP+LGS versus CSII falls below commonly cited willingness-to-pay thresholds. Therefore, in Denmark, the use of SAP+LGS is likely to be considered cost-effective relative to CSII for patients with T1D who are either hyperglycemic, despite CSII use, or who experience frequent severe hypoglycemic events.

Cost-effectiveness of continuous subcutaneous insulin infusion in people with type 2 diabetes in the Netherlands.

AIMS: Up to 30% of insulin-treated type 2 diabetes patients are unable to achieve HbA1c targets despite optimization of insulin multiple daily injections (MDI). For these patients the use of continuous subcutaneous insulin infusion (CSII) represents a useful but under-utilized alternative. The aim of the present analysis was to examine the cost-effectiveness of initiating CSII in type 2 diabetes patients failing to achieve good glycemic control on MDI in the Netherlands. METHODS: Long-term projections were made using the IMS CORE Diabetes Model. Clinical input data were sourced from the OpT2mise trial. The analysis was performed over a lifetime time horizon. The discount rates applied to future costs and clinical outcomes were 4% and 1.5% per annum, respectively. RESULTS: CSII was associated with improved quality-adjusted life expectancy compared with MDI (9.38 quality-adjusted life years [QALYs] vs 8.95 QALYs, respectively). The breakdown of costs indicated that ∼50% of costs were attributable to diabetes-related complications. Higher acquisition costs of CSII vs MDI were partially offset by the reduction in complications. The ICER was estimated at EUR 62,895 per QALY gained and EUR 60,474 per QALY gained when indirect costs were included. CONCLUSIONS: In the Netherlands, CSII represents a cost-effective option in patients with type 2 diabetes who continue to have poorly-controlled HbA1c despite optimization of MDI. Since the ICER falls below the willingness-to-pay threshold of EUR 80,000 per QALY gained, CSII is likely to represent good-value for money in the treatment of poorly-controlled T2D patients compared with MDI.

Cost-effectiveness of continuous subcutaneous insulin infusion versus multiple daily injections of insulin in Type 1 diabetes: a systematic review.

AIM: Continuous subcutaneous insulin infusion (CSII) is increasingly used in clinical practice for the management of selected patients with Type 1 diabetes. Several cost-effectiveness studies comparing CSII vs. multiple insulin injections (MDI) have been reported. The aim was systematically to review these analyses and test the hypothesis that CSII is a cost-effective use of healthcare resources across settings. METHODS: A literature review was performed using MEDLINE, Cochrane Library and other databases. No time limit or language restrictions were applied. After two rounds of screening, 11 cost-effectiveness analyses were included in the final review, of which nine used the CORE Diabetes Model. A narrative synthesis was conducted and mean cost effectiveness calculated. RESULTS: CSII was considered cost-effective vs. MDI in Type 1 diabetes in all 11 studies in 8 countries, with a mean (95% CI) incremental cost effectiveness ratio of €30 862 (17 997-43 727), US$40 143 (23 409-56 876) per quality-adjusted life year (QALY) gained. CSII was associated with improved life expectancy and quality-adjusted life expectancy (0.4-1.1 QALYs in adults), driven by lower HbA(1c) and lower frequency of hypoglycaemic events vs. MDI. CSII was associated with higher lifetime direct costs due to higher treatment costs but this was partially offset by cost-savings from reduced diabetes-related complications. CONCLUSIONS: Published cost-effectiveness analyses show that in Type 1 diabetes CSII is cost-effective vs. MDI across a number of settings for patients who have poor glycaemic control and/or problematic hypoglycaemia on MDI, with cost-effectiveness highly sensitive to the reduction in HbA1c and hypoglycaemia frequency associated with CSII.

Assessment of the association between glycemic variability and diabetes-related complications in type 1 and type 2 diabetes.

Chronic hyperglycemia is the main risk factor for the development of diabetes-related complications in both type 1 and type 2 diabetes, but it is thought that frequent or large glucose fluctuations may contribute independently to diabetes-related complications. A systematic literature review was performed using the PubMed, EMBASE and Cochrane Library databases with searches limited to studies published from June 2002 to March 2014, in English and including ≥50 patients. Twenty eight articles were included in the final review. Eighteen studies reported the association between glucose variability and diabetes-related complications exclusively in type 2 diabetes. A positive association between increased variability and microvascular complications and coronary artery disease was consistently reported. Associations between glucose variability and other macrovascular complications were inconsistent in type 2 diabetes. Seven studies examined the association between glucose variability and complications exclusively in type 1 diabetes. Increased glucose variability appears to play a minimal role in the development of micro- and macrovascular complications in type 1 diabetes. Consistent findings suggest that in type 2 diabetes glucose variability is associated with development of microvascular complications. The role of increased glucose variability in terms of microvascular and macrovascular complications in type 1 diabetes is less clear; more data in are needed.

Influence of renal function on long-term graft survival and patient survival in renal transplant recipients.

OBJECTIVES: Renal function post kidney transplantation is an outcome of interest for both clinicians and regulators evaluating immunosuppressive treatments post-transplantation. The current review sought to provide a synopsis of currently available literature examining the relationship between post-transplantation renal function and long-term graft survival and patient survival. METHODS: A systematic literature review was performed using the PubMed, EMBASE and Cochrane Library databases. The search strategy was designed based on high level Medical Subject Heading (MeSH) terms and designed to capture studies published in English to 2012 and identified a total of 2683 unique hits; for inclusion studies were required to have >100 patients. Following two rounds of screening, a total of 27 studies were included in the final review (26 of which were identified via the literature review and one study was identified via searches of the reference sections of included studies). RESULTS: The consensus among studies was that lower post-transplantation GFR, in particular 12 month GFR, was consistently and significantly associated with an increased risk for overall graft loss, death-censored graft loss and all-cause mortality in both univariate and multivariate analyses. The magnitude of the association between reduced GFR and outcomes was greater for death-censored graft loss versus overall graft loss and for graft loss in comparison with overall patient mortality. The predictive utility of GFR alone in predicting long-term outcomes was reported to be limited. CONCLUSIONS: Lower GFR and greater rates of decline in GFR post-transplantation are associated with an increased risk for graft loss (overall and death-censored) and all-cause mortality; however, the predictive utility of GFR alone in predicting long-term outcomes is limited.

Long-term cost-effectiveness of insulin detemir versus NPH insulin in type 2 diabetes in Sweden.

AIM: To evaluate the cost-effectiveness of insulin detemir vs. NPH insulin once daily, in patients with type 2 diabetes in the Swedish setting based on clinical data from a published randomized controlled trial. METHODS: Projections of long-term outcomes were made using the IMS CORE Diabetes Model (CDM), based on clinical data from a 26-week randomized controlled trial that compared once daily insulin detemir and NPH insulin, when used to intensify insulin treatment in 271 patients with type 2 diabetes and body mass index (BMI) 25-40 kg/m(2). Trial results showed that insulin detemir was associated with a significantly lower incidence of hypoglycemic events and significantly less weight gain in comparison with NPH insulin. The analysis was conducted from a third party payer perspective and the base case analysis was performed over a time horizon of 40 years and future costs and clinical outcomes were discounted at a rate of 3% per year. RESULTS: Insulin detemir was associated with higher mean (SD) quality-adjusted life expectancy (5.42 [0.10] vs. 5.31 [0.10] quality-adjusted life years [QALYs]) and lower overall costs (SEK 378,539 [10,372] vs. SEK 384,216 [11,230]; EUR 33,794 and EUR 34,300, respectively, where 1 EUR=11.2015 SEK) compared with NPH insulin. Sensitivity analysis showed that the principal driver of the benefits associated with insulin detemir was the lower rate of hypoglycemic events (major and minor events) vs. NPH insulin, suggesting that detemir might also be cost-saving over a shorter time horizon. Limitations of the analysis include the use of data from a trial outside Sweden in the Swedish setting. CONCLUSIONS: Based on clinical input data derived from a previously published randomized controlled trial, it is likely that in the Swedish setting insulin detemir would be cost-saving in comparison with NPH insulin for the treatment of patients with type 2 diabetes.

Anti-CD3 monoclonal antibody treatment in newly diagnosed Type 1 diabetes patients: a hypothetical modelling analysis.

AIMS: Although limited clinical data exist for anti-CD3 monoclonal antibody therapies, it is believed that they may influence glycaemic control, endogenous insulin secretion and hypoglycaemic event rates in individuals newly diagnosed with Type 1 diabetes. In the absence of suitable empirical evidence, the objective of this study was to estimate the potential long-term clinical outcomes associated with treatment via a hypothetical modelling analysis. METHODS: Analyses were performed using a published and validated computer simulation model of diabetes in a hypothetical US cohort based on published literature and expert opinion. The efficacy of anti-CD3 monoclonal antibody treatment was estimated from clinical data and expert opinion and simulations were performed over a 60-year time horizon. The impact on quality of life associated with treatment was also captured via published utility values. RESULTS: Assuming that a treatment course of an anti-CD3 monoclonal antibody produced an initial reduction in glycated haemoglobin of -0.8%, and that the effects persisted for up to 5 years, treatment was projected to lead to an increase in undiscounted life expectancy of 0.43 years and an increase in quality-adjusted life expectancy of 0.36 quality-adjusted life years compared with conventional exogenous insulin. CONCLUSIONS: A course of a hypothetical anti-CD3 monoclonal antibody treatment associated with improved glycaemic control and, potentially, the preservation of pancreatic beta-cell function was estimated to lead to improved life expectancy and quality-adjusted life expectancy compared with conventional treatment in patients with newly diagnosed Type 1 diabetes.

Evaluation of exenatide vs. insulin glargine in type 2 diabetes: cost-effectiveness analysis in the German setting.

OBJECTIVES: The objective of this analysis was to determine the cost-effectiveness of exenatide vs. insulin glargine in patients with type 2 diabetes failing to achieve glycaemic control with oral antidiabetic agents, in the German setting, from a third-party payer perspective. METHODS: Data from a published randomized controlled trial were used in combination with a published, validated computer simulation model of type 2 diabetes to project clinical and cost outcomes over a time horizon of 10 years. Cost data were obtained from published literature and expert opinion. Clinical and cost outcomes were discounted at 5% per annum. Sensitivity analyses were performed to establish key drivers and parameters. RESULTS: Treatment with exenatide compared with insulin glargine was projected to be associated with improvements in life expectancy of 0.016 years and quality-adjusted life expectancy of 0.280 quality-adjusted life years (QALYs), increased lifetime direct medical costs of euro 3854 (euro 22 095 vs. euro 18 242) and an incremental cost-effectiveness ratio (ICER) of euro 13 746 per QALY. If quality of life was not taken into account, exenatide was associated with an ICER of euro 238 201 per life year gained vs. insulin glargine. Sensitivity analyses revealed that outcomes were most sensitive to changes in assumptions for (dis)utility values relating to weight change and the rate of self-monitored blood glucose testing. CONCLUSIONS: Exenatide was projected to be associated with similar clinical outcomes and increased costs compared with insulin glargine. Analysis of cost-effectiveness from a third-party perspective suggests that exenatide is likely to represent good value for money in the German setting.