Validation of the IMS CORE Diabetes Model.

BACKGROUND: The IMS CORE Diabetes Model (CDM) is a widely published and validated simulation model applied in both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) analyses. Validation to external studies is an important part of demonstrating model credibility. OBJECTIVE: Because the CDM is widely used to estimate long-term clinical outcomes in diabetes patients, the objective of this analysis was to validate the CDM to contemporary outcomes studies, including those with long-term follow-up periods. METHODS: A total of 112 validation simulations were performed, stratified by study follow-up duration. For long-term results (≥15-year follow-up), simulation cohorts representing baseline Diabetes Control and Complications Trial (DCCT) and United Kingdom Prospective Diabetes Study (UKPDS) cohorts were generated and intensive and conventional treatment arms were defined in the CDM. Predicted versus observed macrovascular and microvascular complications and all-cause mortality were assessed using the coefficient of determination (R(2)) goodness-of-fit measure. RESULTS: Across all validation studies, the CDM simulations produced an R(2) statistic of 0.90. For validation studies with a follow-up duration of less than 15 years, R(2) values of 0.90 and 0.88 were achieved for T1DM and T2DM respectively. In T1DM, validating against 30-year outcomes data (DCCT) resulted in an R(2) of 0.72. In T2DM, validating against 20-year outcomes data (UKPDS) resulted in an R(2) of 0.92. CONCLUSIONS: This analysis supports the CDM as a credible tool for predicting the absolute number of clinical events in DCCT- and UKPDS-like populations. With increasing incidence of diabetes worldwide, the CDM is particularly important for health care decision makers, for whom the robust evaluation of health care policies is essential.

Cost-effectiveness of aliskiren in type 2 diabetes, hypertension, and albuminuria.

The Aliskiren in the Evaluation of Proteinuria in Diabetes (AVOID) trial demonstrated that adding aliskiren, an oral direct renin inhibitor, at a dosage of 300 mg/d to the highest approved dosage of losartan and optimal antihypertensive therapy reduces albuminuria over 6 mo among patients with type 2 diabetes, hypertension, and albuminuria. The cost-effectiveness of this therapy, however, is unknown. Here, we used a Markov model to project progression to ESRD, life years, quality-adjusted life years, and lifetime costs for aliskiren plus losartan versus losartan. We used data from the AVOID study and the Irbesartan in Diabetic Nephropathy Trial (IDNT) to estimate probabilities of progression of renal disease. We estimated probabilities of mortality for ESRD and other comorbidities using data from the US Renal Data System, US Vital Statistics, and published studies. We based pharmacy costs on wholesale acquisition costs and based costs of ESRD and transplantation on data from the US Renal Data System. We found that adding aliskiren to losartan increased time free of ESRD, life expectancy, and quality-adjusted life expectancy by 0.1772, 0.1021, and 0.0967 yr, respectively. Total expected lifetime health care costs increased by $2952, reflecting the higher pharmacy costs of aliskiren and losartan ($7769), which were partially offset by savings in costs of ESRD ($4860). We estimated the cost-effectiveness of aliskiren to be $30,500 per quality-adjusted life year gained. In conclusion, adding aliskiren to losartan and optimal therapy in patients with type 2 diabetes, hypertension, and albuminuria may be cost-effective from a US health care system perspective.

Cost-effectiveness of switching to biphasic insulin aspart 30 from human insulin in patients with poorly controlled type 2 diabetes in South Korea.

OBJECTIVES: To estimate the cost-effectiveness of switching patients with poorly controlled type 2 diabetes mellitus from human insulin (HI) to biphasic insulin aspart 30 (BIAsp 30) in South Korea. METHODS: A published and validated diabetes computer simulation model (the IMS CORE Diabetes Model) was used to evaluate the long-term clinical and economic outcomes associated with switching to BIAsp 30, using treatment effects from the South Korean subgroup of the Physician's Routine Evaluation of Safety and Efficacy of NovoMix 30 Therapy study and cost data collected through primary research. Outcomes included life expectancy, quality-adjusted life expectancy, incidence of complications, direct medical costs, and cost-effectiveness. Analyses were performed from a third-party payer perspective over a 30-year time horizon. Future costs and clinical benefits were discounted at 5% per annum. Extensive sensitivity analyses were performed. RESULTS: Switching patients uncontrolled on HI to BIAsp 30 was projected to increase discounted mean life expectancy by 0.15 +/- 0.18 years per patient (8.62 +/- 0.13 years vs. 8.47 +/- 0.13 years) and improve discounted mean quality-adjusted life expectancy by 0.30 +/- 0.12 quality-adjusted life-years (QALYs) per patient (5.68 +/- 0.09 QALYs vs. 5.38 +/- 0.09 QALYs). Conversion to BIAsp 30 was associated with a mean increase in direct costs of South Korean Won (KRW) 1,777,323 +/- 359,209 over patient lifetimes. BIAsp 30 was associated with an incremental cost-effectiveness ratio of KRW5,916,758 per QALY gained versus HI. CONCLUSION: Switching patients uncontrolled on HI to BIAsp 30 was projected to improve life expectancy and quality-adjusted life expectancy. This analysis suggests that BIAsp 30 could be a cost-effective treatment option in type 2 diabetes patients poorly controlled on HI in South Korea.

Cost-effectiveness of switching to biphasic insulin aspart in poorly-controlled type 2 diabetes patients in China.

INTRODUCTION: Type 2 diabetes is an increasing problem in China, yet there is a paucity of data regarding the cost-effectiveness of pharmacological interventions in the Chinese setting. METHODS: Previous data were obtained from PRESENT (Physicians' Routine Evaluation of Safety and Efficacy of NovoMix 30 Therapy), a multi-country, single-arm, observational study where type 2 diabetes patients poorly controlled with biphasic human insulin (BHI) were converted to biphasic insulin aspart 30 (BIAsp30); the Chinese subgroup experienced an improvement in HbA(1c) and a reduction in hypoglycaemic events. A published and validated computer simulation model of diabetes (the CORE Diabetes Model) was used to estimate the long-term clinical and cost consequences of switching to BIAsp30 from BHI in the Chinese setting. Treatment effects and patient characteristics were derived from PRESENT and country-specific published sources. Primary research was performed to ascertain patient management practices and diabetes-related complication costs. Risks of modelled complications were derived from landmark clinical trials and epidemiological studies. Costs and clinical projections were made over patient lifetimes from a third-party payer perspective and discounted at 3% annually. Extensive sensitivity analyses were performed. RESULTS: Conversion to BIAsp30 from BHI was projected to improve discounted life expectancy by 0.38 years per patient (9.91 vs 9.53 years) and quality-adjusted life expectancy by 0.91 quality-adjusted life years (QALYs) per patient (6.32 vs 5.41 QALYs). Conversion to BIAsp30 was associated with increased direct medical costs of Chinese Yuan (CNY) 1751 per patient, due to higher pharmacy and management costs (CNY +19,007), offset by reduced diabetes-related complication costs (CNY -17,254) over patient lifetimes. BIAsp30 was associated with an incremental cost-effectiveness ratio of CNY 1926 per QALY gained. CONCLUSION: BIAsp30 was projected to substantially improve clinical outcomes but was associated with increased lifetime medical costs. BIAsp30 would be considered cost-effective in China given a willingness-to-pay threshold of CNY 100,000 per QALY gained in type 2 diabetes patients poorly controlled on BHI.

Therapy conversion to biphasic insulin aspart 30 improves long-term outcomes and reduces the costs of type 2 diabetes in Saudi Arabia.

OBJECTIVE: An observational study in Saudi Arabia indicated that conversion to biphasic insulin aspart 30 (BIAsp 30) from human insulin (HI) was associated with improvement of glycaemic control. METHODS: A validated computer simulation model of diabetes was used to project long-term outcomes (such as quality-adjusted life expectancy and direct medical costs) based on patient characteristics and treatment effects observed in the Saudi Arabian PRESENT subgroup (n=598). Baseline prevalence of comorbidities was obtained from published sources. Primary research was performed in Riyadh and Jeddah to derive diabetes-related complication costs and patient management practices. RESULTS: Conversion to BIAsp 30 from HI was projected to increase life expectancy by 0.62 years (11.77 +/- 0.20 vs. 11.15 +/- 0.19 years) and quality-adjusted life expectancy by 0.96 quality-adjusted life years (QALYs) (7.03 +/- 0.12 vs. 6.07 +/- 0.11 QALYs). Direct medical cost savings of Saudi Arabian Riyals (SAR) 53,879 per patient were projected for conversion to BIAsp 30 therapy (SAR 84,761 +/- 3102 vs. SAR 138,640 +/- 4102 per patient). Cost savings were driven by lower costs of hypoglycaemia (SAR 286 vs. SAR 57,437 per patient), and lower costs of renal complications (SAR 18,848 vs. SAR 31,228) over patient lifetimes. CONCLUSION: Conversion to BIAsp 30 from HI was projected to improve life expectancy and quality-adjusted life expectancy while reducing lifetime direct medical costs.

Cost-effectiveness of once daily GLP-1 receptor agonist lixisenatide compared to bolus insulin both in combination with basal insulin for the treatment of patients with type 2 diabetes in Norway.

BACKGROUND: Lixisenatide is a potent, selective and short-acting once daily prandial glucagon-like peptide-1 receptor agonist which lowers glycohemoglobin and body weight by clinically significant amounts in patients with type 2 diabetes treated with basal insulin, with limited risk of hypoglycemia. OBJECTIVE: To assess the cost-effectiveness of lixisenatide versus bolus insulin, both in combination with basal insulin, in patients with type 2 diabetes in Norway. METHODS: The IMS CORE Diabetes Model, a non-product-specific and validated simulation model, was used to make clinical and cost projections. Transition probabilities, risk adjustments and the progression of complication risk factors were derived from the UK Prospective Diabetes Study, supplemented with Norwegian data. Patients were assumed to receive combination treatment with basal insulin, lixisenatide or bolus insulin therapy for 3 years, followed by intensification of a basal-bolus insulin regimen for their remaining lifetime. Simulated healthcare costs, taken from the public payer perspective, were derived from microcosting and diagnosis related groups, discounted at 4% per annum and reported in Norwegian krone (NOK). Productivity costs were also captured based on extractions from the Norwegian Labor and Welfare Administration. Health state utilities were derived from a systematic literature review. Sensitivity and scenario analyses were performed. RESULTS: Lixisenatide in combination with basal insulin was associated with increased quality-adjusted life years (QALYs) and reduced lifetime healthcare costs compared to bolus insulin in combination with basal insulin in patients with Type 2 diabetes, and can be considered dominant. The net monetary benefit of lixisenatide versus bolus insulin was NOK 39,369 per patient. Results were sensitive to discounting, the application of excess body weight associated disutility and uncertainty surrounding the changes in HbA1c. CONCLUSIONS: Lixisenatide may be considered an economically efficient therapy in combination with basal insulin in the Norwegian setting, due to cost savings, weight loss and associated gains in health-related quality of life.

Economic impact of severe and non-severe hypoglycemia in patients with Type 1 and Type 2 diabetes in the United States.

OBJECTIVE: To identify the direct and indirect costs of hypoglycemia in patients with Type 1 or Type 2 diabetes mellitus (DM) in the US setting. METHODS: A literature review was conducted to identify and review studies that reported data on the economic burden of hypoglycemia and the related medical resource consumption or productivity loss related to hypoglycemia in patients with Type 1 or Type 2 DM. Relevant information was collated in an economic model to assess the direct and indirect costs following severe and non-severe hypoglycemic events in Type 1 and Type 2 DM. RESULTS: Detailed evidence of the medical cost burden of hypoglycemic events was identified from 14 studies. For both Type 1 and Type 2 DM, episodes requiring assistance from a healthcare practitioner were identified as particularly costly and amounted to $1161 per episode (direct costs) compared with episode costs of $66 and $11 for events requiring third-party (non-medical) assistance and events managed by self-treatment, respectively. Indirect costs associated with severe hypoglycemia requiring non-medical assistance, severe hypoglycemia requiring medical assistance, and non-severe hypoglycemia were predicted to be $242, $160, and $11 for patients with Type 1 diabetes and $579, $176, and $11 for patients with Type 2 diabetes, respectively. CONCLUSION: Both severe and non-severe hypoglycemia incur substantial healthcare costs. Failure to account for these costs may under-estimate the value of management strategies that minimize hypoglycemia risk.

Long-term clinical and economic outcomes associated with liraglutide versus sitagliptin therapy when added to metformin in the treatment of type 2 diabetes: a CORE Diabetes Model analysis.

BACKGROUND: A recent open-label, parallel group trial showed that liraglutide is superior to sitagliptin for reduction of HbA1c, and is well tolerated with minimum risk of hypoglycemia. Although these findings support the use of liraglutide as an effective GLP-1 agent to add to metformin, the value of liraglutide needs to be quantified in the framework of a cost-effectiveness (CE) analysis in a US setting. OBJECTIVE: This current study sets out to assess the long-term cost-effectiveness outcomes of liraglutide vs sitagliptin based on treatment effects data from the 1860-LIRA-DPP-4 52-week trial. METHODS: The IMS CORE Diabetes Model (CDM), a non-product-specific, validated computer simulation model that projects the long-term outcomes related to interventions for type 2 diabetes, is used for simulation of these interventions. In the model, patients were treated initially on one of the three treatment options: liraglutide 1.2 mg daily, 1.8 mg daily, or sitagliptin 100 mg daily, each used as add-on therapy to metformin for 5 years. After 5 years all patients switched to basal insulin treatment for the remainder of the simulation (35-year time horizon overall). Incremental cost-effectiveness ratios (ICERs) were generated for liraglutide 1.2 mg compared with sitagliptin and liraglutide 1.8 mg compared with sitagliptin. Transition probabilities, health state utility values, and complication costs were obtained from published sources. All outcomes were discounted at 3% per annum, and the analysis was conducted from the perspective of a third-party payer in the US. Sensitivity analyses were performed to test robustness of the base case scenario. RESULTS: For liraglutide 1.8 mg vs sitagliptin, the ICER was $37,234 per QALY gained, while for liraglutide 1.2 mg vs sitagliptin, the ICER was $25,742 per QALY gained. In all sensitivity analyses, including setting the change in HbA1c to the lower limits of the 95% confidence intervals, the ICERs remained below US$ 50,000/QALY, a commonly accepted threshold in the US, except for the shortest time horizon of 10 years. CONCLUSIONS: The availability of liraglutide 1.2 mg and 1.8 mg with improved efficacy profiles over sitagliptin could improve patient care, with the incremental cost effectiveness ratio below $50,000 per QALY gained as add-on to metformin.

Cost-utility of exenatide once weekly compared with insulin glargine in patients with type 2 diabetes in the UK.

OBJECTIVE: To compare the cost-utility of exenatide once weekly (EQW) and insulin glargine in patients with type 2 diabetes in the United Kingdom (UK). RESEARCH DESIGN AND METHODS: The IMS CORE Diabetes Model was used to project clinical and economic outcomes for patients with type 2 diabetes treated with EQW or insulin glargine. Treatment effects and patient baseline characteristics (mean age: 58 years, mean glycohaemoglobin: 8.3%) were taken from the DURATION-3 study. Unit costs and health state utility values were derived from published sources. As the price of EQW is not yet known, the prices of two currently available glucagon-like peptide-1 products were used as benchmarks. To reflect diabetes progression, patients started on EQW switched to insulin glargine after 5 years. The analysis was conducted from the perspective of the UK National Health Service over a time horizon of 50 years with costs and outcomes discounted at 3.5%. Sensitivity analyses explored the impact of changes in input data and assumptions and investigated the cost utility of EQW in specific body mass index (BMI) subgroups. MAIN OUTCOME MEASURES: Incremental cost-effectiveness ratio (ICER) for EQW compared with insulin glargine. RESULTS: At a price equivalent to liraglutide 1.2 mg, EQW was more effective and more costly than insulin glargine, with a base case ICER of £10,597 per quality-adjusted life-year (QALY) gained. EQW was associated with an increased time to development of any diabetes-related complication of 0.21 years, compared with insulin glargine. Three BMI subgroups investigated (<30, 30-35 and >35 kg/m(2)) reported ICERs for EQW compared with insulin glargine ranging from £9425 to £12,956 per QALY gained. CONCLUSIONS: At the prices investigated, the cost per QALY gained for EQW when compared with insulin glargine in type 2 diabetes in the UK setting, was within the range normally considered cost effective by NICE. Cost effectiveness in practice will depend on the final price of EQW and the extent to which benefits observed in short-term randomised trials are replicated in long-term use.

Cost-effectiveness of switching to biphasic insulin aspart from human premix insulin in a US setting.

OBJECTIVES: To evaluate the cost-effectiveness of switching to biphasic insulin aspart (BIAsp 30) from human premix insulin for type 2 diabetes patients in the United States (US) setting. METHODS: The previously published and validated IMS Core Diabetes Model was used to project life expectancy, quality-adjusted life expectancy (QALE) and costs over 30 years. Patient characteristics and treatment effects were based on Canadian patients included the IMPROVE observational study (n = 311). Mean glycohaemoglobin (HbA(1c)) was 8.4%, duration of diabetes 16 years and prevalence of complications high at baseline. Simulations were conducted from the perspective of a third-party payer, with costs accounted in 2008 US dollars ($). RESULTS: BIAsp 30 was projected to improve life expectancy by 0.202 years and QALE by 0.301 quality-adjusted life-years (QALYs), due to a reduced incidence of most diabetes-related complications. BIAsp 30 was associated with increased lifetime direct medical costs ($76,517 vs. 67,518) and an incremental cost-effectiveness ratio of $29,870 per QALY gained. Long-term outcomes were sensitive to the impact of BIAsp 30 on hypoglycaemia and changes in HbA(1c). CONCLUSIONS: BIAsp 30 may represent a cost-effective treatment option in the US setting for advanced type 2 diabetes patients experiencing poor glycaemic control or hypoglycaemia on human premix insulin. LIMITATIONS: The application of treatment effect data derived from a Canadian cohort to the US setting was a limitation of the cost-effectiveness analysis. The findings of this cost-effectiveness analysis are not applicable to insulin-naïve diabetes patients.

Cost-effectiveness of biphasic insulin aspart versus insulin glargine in patients with type 2 diabetes in China.

BACKGROUND: The OnceMix and INITIATE studies have indicated that biphasic insulin aspart 30 (BIAsp 30) is more effective than insulin glargine (IGlarg), in terms of glycohemoglobin reductions, in patients with type 2 diabetes initiating insulin therapy. The cost-effectiveness of BIAsp 30 versus IGlarg in the Chinese setting is estimated here. METHODS: The validated and peer-reviewed CORE Diabetes Model was used. The nephropathy, retinopathy, and stroke submodels were modified to incorporate available Chinese clinical data. Diabetes complication costs were derived from hospital surveys in Beijing and Chengdu. Simulated cohorts and insulin treatment effects were based on the OnceMix study for once-daily BIAsp 30 versus IGlarg and on the INITIATE study for twice-daily BIAsp 30 versus IGlarg. Life expectancy and direct medical costs were calculated. Projections were made over 30-year time horizons, with costs and life years discounted at 3% annually. Extensive sensitivity analyses were performed, including adjustments to cardiovascular risk for Chinese ethnicity. RESULTS: Once-daily BIAsp 30 increased life expectancy by 0.04 years (12.37 vs. 12.33 years) and reduced direct medical costs by Chinese Yuan (CNY) 59,710 per patient (CNY 229,911 vs. CNY 289,621 per patient) compared with IGlarg in the OnceMix-based analysis. Twice-daily BIAsp 30 increased life expectancy by 0.08 years (12.99 vs. 12.91 years) and reduced direct medical costs by CNY 107,349 per patient (CNY 303,142 vs. CNY 410,491 per patient) compared with IGlarg in the INITIATE-based analysis. Improvements in life expectancy were driven by reduced incidences of most diabetes-related complications. Cost savings were attributable to lower lifetime insulin costs for BIAsp 30 compared with IGlarg in China. Lowered cardiovascular risk for Chinese ethnicity reduced the projected clinical improvements for BIAsp 30 but increased treatment-related lifetime cost savings. CONCLUSIONS: BIAsp 30, either once- or twice-daily, improved projected life expectancy and reduced projected costs compared with IGlarg in the Chinese setting.

Cost-effectiveness of insulin aspart versus human soluble insulin in type 2 diabetes in four European countries: subgroup analyses from the PREDICTIVE study.

OBJECTIVES: To evaluate the long-term health economic outcomes associated with insulin aspart (IAsp) compared to human soluble insulin (HI) in type 2 diabetes patients on basal-bolus therapy in Sweden, Spain, Italy and Poland. METHODS: A published computer simulation model of diabetes was used to predict life expectancy, quality-adjusted life expectancy and incidence of diabetes-related complications. Baseline cohort characteristics (age 61.6 years, duration of diabetes 13.2 years, 45.1% male, HbA(1c) 8.2%, BMI 29.8 kg/m(2)) and treatment effects were derived from the PREDICTIVE observational study. Country-specific complication costs were derived from published sources. The analyses were run over 35-year time horizons from third-party payer perspectives in Spain, Italy and Poland and from a societal perspective in Sweden. Future costs and clinical benefits were discounted at country-specific discount rates. Sensitivity analyses were performed. RESULTS: IAsp was associated with improvements in discounted life expectancy and quality-adjusted life expectancy, and a reduced incidence of most diabetes-related complications versus HI in all four settings. IAsp was associated with societal cost-savings in Sweden (SEK 2470), direct medical cost-savings in Sweden and Spain (SEK 8248 and euro 1382, respectively), but increased direct costs in Italy (euro 2235) and Poland (euro 743). IAsp was associated with improved quality-adjusted life expectancy in Sweden (0.077 QALYs), Spain (0.080 QALYs), Italy (0.120 QALYs) and Poland (0.003 QALYs). CONCLUSIONS: IAsp was dominant versus HI in both Sweden and Spain, would be considered cost-effective in Italy with an incremental cost-effectiveness ratio of euro 18,597 per QALY gained, but would not be considered cost-effective in Poland.