Cost-Effectiveness of Oral Nirmatrelvir/Ritonavir in Patients at High Risk for Progression to Severe COVID-19 in the United States.

OBJECTIVES: Nirmatrelvir/ritonavir (NMV/r) is an orally administered antiviral indicated for the outpatient treatment of patients with mild-to-moderate COVID-19 at high risk for disease progression to severe illness. We estimated the cost-effectiveness of NMV/r versus best supportive care for patients with mild-to-moderate COVID-19 at high risk for progression to severe illness from a US health sector perspective. METHODS: A cost-effectiveness model was developed using a short-term decision-tree (1 year) followed by a lifetime 2-state Markov model (alive and dead). The short-term decision-tree captured costs and outcomes associated with the primary infection and healthcare utilization; survivors of the short-term decision-tree were followed until death assuming US quality-adjusted life years (QALYs), adjusted in the short-term for survivors of mechanical ventilation. Baseline rate of hospitalization and NMV/r effectiveness were taken from an Omicron-era US real-world study. Remaining inputs were informed by previous COVID-19 studies and publicly available US sources. Sensitivity analyses were conducted for all model inputs to test the robustness of model results. RESULTS: NMV/r was found to decrease COVID-19 related hospitalizations (-0.027 per infected case) increase QALYs (+0.030), decrease hospitalization costs (-$1110), and increase total treatment cost (+$271), resulting in an incremental cost-effectiveness ratio of $8931/QALY. Results were most sensitive to baseline risk of hospitalization and NMV/r treatment effectiveness parameters. The probabilistic analysis indicated that NMV/r has a >99% probability of being cost-effective at a $100 000 willingness-to-pay threshold. CONCLUSIONS: NMV/r is cost-effective vs best supportive care for patients at high risk for severe COVID-19 from a US health sector perspective.

Estimating the value of sodium-glucose cotransporter-2 inhibitors within the context of contemporary guidelines and the totality of evidence.

AIMS: To comprehensively estimate the cost-effectiveness of sodium glucose cotransporter-2 (SGLT2) inhibitor usage in the management of type 2 diabetes mellitus (T2DM) at established clinical review points, incorporating the totality of proven health benefits. MATERIALS AND METHODS: This study considered the cardio- and reno-protective effects of SGLT2 inhibitors using the Cardiff type 2 diabetes model. Conventional cost-effectiveness evaluations were undertaken for eligible populations at relevant intensification points reflecting the 2022 guidelines versus the 2015 National Institute of Health and Care Excellence (NICE) guidelines; incremental cost-effectiveness ratio lifetime trajectories and timepoints for complete cost-offset were estimated for each pathway. Treatment effects, utility decrements and costs (applied additively and discounted at 3.5%) were sourced from the published literature. RESULTS: For all subpopulations on treatment pathways reflecting the NG28-2022 guidelines, SGLT2 inhibitor introduction was cost-effective, becoming cost-saving between 2 and 16 years post-initiation. Despite increases in pharmacy costs, predicted lifetime costs were lower than for pathways reflecting the NG28-2015 guidelines, driven by a reduction in heart failure hospitalization and chronic kidney disease costs. Incremental gains in quality-adjusted life years (ranging from 0.58-1.12) resulted in dominance for the updated NG28-2022 guidance in all scenarios. CONCLUSIONS: Our results show that SGLT2 inhibitors have the potential to lower healthcare costs while improving health outcomes in eligible patient subpopulations.

Computer Modeling of Diabetes and Its Transparency: A Report on the Eighth Mount Hood Challenge.

OBJECTIVES: The Eighth Mount Hood Challenge (held in St. Gallen, Switzerland, in September 2016) evaluated the transparency of model input documentation from two published health economics studies and developed guidelines for improving transparency in the reporting of input data underlying model-based economic analyses in diabetes. METHODS: Participating modeling groups were asked to reproduce the results of two published studies using the input data described in those articles. Gaps in input data were filled with assumptions reported by the modeling groups. Goodness of fit between the results reported in the target studies and the groups' replicated outputs was evaluated using the slope of linear regression line and the coefficient of determination (R2). After a general discussion of the results, a diabetes-specific checklist for the transparency of model input was developed. RESULTS: Seven groups participated in the transparency challenge. The reporting of key model input parameters in the two studies, including the baseline characteristics of simulated patients, treatment effect and treatment intensification threshold assumptions, treatment effect evolution, prediction of complications and costs data, was inadequately transparent (and often missing altogether). Not surprisingly, goodness of fit was better for the study that reported its input data with more transparency. To improve the transparency in diabetes modeling, the Diabetes Modeling Input Checklist listing the minimal input data required for reproducibility in most diabetes modeling applications was developed. CONCLUSIONS: Transparency of diabetes model inputs is important to the reproducibility and credibility of simulation results. In the Eighth Mount Hood Challenge, the Diabetes Modeling Input Checklist was developed with the goal of improving the transparency of input data reporting and reproducibility of diabetes simulation model results.

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.

Computer modeling of diabetes and its complications: a report on the Fifth Mount Hood challenge meeting.

OBJECTIVES: The Mount Hood Challenge meetings provide a forum for computer modelers of diabetes to discuss and compare models, to assess predictions against data from clinical trials and other studies, and to identify key future developments in the field. This article reports the proceedings of the Fifth Mount Hood Challenge in 2010. METHODS: Eight modeling groups participated. Each group was given four modeling challenges to perform (in type 2 diabetes): to simulate a trial of a lipid-lowering intervention (The Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in Non-Insulin-Dependent Diabetes Mellitus [ASPEN]), to simulate a trial of a blood glucose-lowering intervention (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation [ADVANCE]), to simulate a trial of a blood pressure-lowering intervention (Cardiovascular Risk in Diabetes [ACCORD]), and (optional) to simulate a second trial of blood glucose-lowering therapy (ACCORD). Model outcomes for each challenge were compared with the published findings of the respective trials. RESULTS: The results of the models varied from each other and, in some cases, from the published trial data in important ways. In general, the models performed well in terms of predicting the relative benefit of interventions, but performed less well in terms of quantifying the absolute risk of complications in patients with type 2 diabetes. Methodological challenges were highlighted including matching trial end-point definitions, the importance of assumptions concerning the progression of risk factors over time, and accurately matching the patient characteristics from each trial. CONCLUSIONS: The Fifth Mount Hood Challenge allowed modelers, through systematic comparison and validation exercises, to identify important differences between models, address key methodological challenges, and discuss avenues of research to improve future diabetes models.

External Validation of the Core Obesity Model to Assess the Cost-Effectiveness of Weight Management Interventions.

BACKGROUND: For economic models to be considered fit for purpose, it is vital that their outputs can be interpreted with confidence by clinicians, budget holders and other stakeholders. Consequently, thorough validation of models should be carried out to enhance confidence in their predictions. Here, we present results of external dependent and independent validations of the Core Obesity Model (COM), which was developed to assess the cost-effectiveness of weight management interventions. OBJECTIVE: The aim was to assess the external validity of the COM (version 6.1), in line with best practice guidance from the International Society for Pharmacoeconomics and Outcomes Research and the Society for Medical Decision Making. METHODS: For validation, suitable sources and outcomes were identified, and used to populate the COM with relevant inputs to allow prediction of study outcomes. Study characteristics were entered into the COM to replicate either the studies used to develop the model (dependent validation) or those not included in the model (independent validation). The concordance between predicted and observed outcomes was then assessed using established statistical methods and generation of mean error estimates. RESULTS: For most outcomes, the predictions of the COM showed good linear correlation with observed outcomes, as evidenced by the high coefficients of determination (R2 values). The independent validation revealed a degree of underestimation in predictions of cardiovascular (CV) disease and mortality, and type 2 diabetes. CONCLUSION: The predictions generated by the risk equations used in the COM showed good concordance both with the studies used to develop the model and with studies not included in the model. In particular, the concordance observed in the external dependent validation suggests that the COM accurately predicts obesity-related event rates observed in the studies used to develop the model. However, the impact of existing CV risk, as well as mortality, is a key area for future refinement of the COM. Our results should increase confidence in the estimates derived from the COM and reduce uncertainty associated with analyses using this model.

Long-term cost-effectiveness of pioglitazone versus placebo in addition to existing diabetes treatment: a US analysis based on PROactive.

OBJECTIVE: To estimate the long-term cost-effectiveness of adding pioglitazone versus placebo to standard treatment in high-risk patients with type 2 diabetes. METHODS: The validated CORE Diabetes Model was modified to project long-term clinical and cost outcomes associated with pioglitazone versus placebo, based on results from PROactive. The model retained basic structure and functionality, with interdependent Markov submodels, Monte Carlo simulation and user interface. Adjustments to submodels were made to accommodate the PROactive primary end points. The analysis was from the perspective of a third party US health-care payer perspective, projected over a lifetime horizon using a 3% annual discount. RESULTS: Over a lifetime horizon, addition of pioglitazone was associated with increased life expectancy (0.237 life-years) and quality-adjusted life expectancy (QALE) [0.166 quality-adjusted life-years (QALYs)] versus placebo. Estimated long-term complication rates showed that pioglitazone reduced the number of events versus placebo for most outcomes. Lifetime total direct costs were marginally higher with pioglitazone versus placebo ($272,694 vs. $265,390, difference $7,305). The incremental cost-effectiveness ratio for pioglitazone versus placebo was $44,105 per QALY gained. Probabilistic sensitivity analysis indicated a 55% likelihood that pioglitazone would be considered cost-effective in the United States, with a willingness to pay of $50,000 per QALY gained. CONCLUSIONS: The addition of pioglitazone to existing therapy in high-risk patients with type 2 diabetes was projected to improve life expectancy, QALE and complication rates compared with placebo. Addition of pioglitazone was in the range generally considered acceptable.

Cost-Effectiveness Analysis of Empagliflozin in Comparison to Sitagliptin and Saxagliptin Based on Cardiovascular Outcome Trials in Patients with Type 2 Diabetes and Established Cardiovascular Disease.

INTRODUCTION: In the cardiovascular outcome trials (CVOT) EMPA-REG OUTCOME, TECOS and SAVOR-TIMI 53, empagliflozin [sodium/glucose cotransporter 2 (SGLT2) inhibitor], sitagliptin and saxagliptin [both dipeptidyl peptidase 4 (DPP4) inhibitors] + standard of care (SoC) were compared to SoC in patients with type 2 diabetes and established cardiovascular disease (CVD). This study assessed the cost-effectiveness (CE) of empagliflozin + SoC in comparison to sitagliptin + SoC and saxagliptin + SoC based on the respective CVOT. METHODS: The IQVIA Core Diabetes Model (CDM) was calibrated to reproduce the CVOT outcomes. EMPA-REG OUTCOME baseline characteristics and CVOT specific treatment effects on risk factors for cardiovascular disease [glycated haemogloblin A1c (HbA1c), body mass index (BMI), blood pressure, lipids] were applied. Three-year observed cardiovascular events of empagliflozin + SoC versus sitagliptin + SoC and saxagliptin + SoC were derived from EMPA-REG OUTCOME and an indirect treatment comparison. Relative risk (RR) adjustments to calibrate the CDM were estimated after consecutive attempts of running the model until the observed and CDM-predicted outcomes matched closely. The drug-specific treatment effects were considered up until treatment switch (when HbA1c reached 8.5%), after which, the United Kingdom Prospective Diabetes Study (UKPDS) 82 risk equations predicted events based on co-existing risk factors and treatment intensification to basal-bolus insulin were applied. The analysis was conducted from the perspective of the UK National Health Service. Costs and quality of life data were derived from UK national sources and published literature. A 50-year time horizon and discount rate of 3.5% were applied. RESULTS: The CDM projected quality-adjusted life years (QALYs) of 6.408, 5.917 and 5.704 and total costs of 50,801 GBP, 47,627 GBP and 48,071 GBP for empagliflozin + SoC, sitagliptin + SoC and saxagliptin + SoC, respectively. The incremental CE ratio (ICER) of empagliflozin + SoC versus sitagliptin + SoC and saxagliptin + SoC was 6464 GBP/QALY and 3878 GBP/QALY, respectively. One-way and probabilistic sensitivity analyses demonstrated the robustness of the results. CONCLUSION: Results suggest that empagliflozin + SoC is cost-effective compared to sitagliptin + SoC and saxagliptin + SoC at a willingness to pay threshold of 20,000 GBP/QALY. FUNDING: Boehringer Ingelheim International GmbH.

Assessing the Burden of Type 2 Diabetes in China Considering the Current Status-Quo Management and Implications of Improved Management Using a Modeling Approach.

BACKGROUND: Recent estimates from the International Diabetes Federation Diabetes Atlas have quantified the total annual expenditure for diabetes in China to be between 354 and 611 billion Chinese yuan (¥) (2015). OBJECTIVES: To use a modeling approach to assess the current and possible future diabetes burden in China on the basis of the current standard of type 2 diabetes (T2D) management (status quo [SQ]) and a series of hypothetical improved management strategies. METHODS: The IQVIA CORE Diabetes Model was used to evaluate the economic burden of T2D in China on the basis of assumptions reflecting the current SQ of T2D management and a number of stepwise improvements. SQ was defined as a scenario in which T2D diagnosis is delayed by 4 years, treatment escalation to maintain glucose control occurs at a 9% glycated hemoglobin (HbA1c) threshold, and there is an overall 60% adherence rate. Stepwise improvements considered immediate diagnosis, declining levels of HbA1c escalation thresholds to 7.0%, and improvements in adherence rate to 80% and 100%. The CORE Diabetes Model was applied on per-capita level to project lifetime costs and clinical outcomes of newly diseased T2D individuals in the Chinese setting. Model outcomes were subsequently annualized and extrapolated to Chinese national level considering the total number of diagnosed individuals with T2D in China. RESULTS: The total annual direct costs attributable to diagnosed T2D in China reflecting current SQ management were estimated at ¥621 billion. Scenarios exploring stepwise improvements from SQ estimated annual net savings of ¥35, ¥35, ¥60, ¥71, ¥75, and ¥106 billion for scenarios exploring immediate diagnosis, HbA1c threshold reductions to 8.0% and 7.0%, adherence rate increase to 80% and 100%, and cardiovascular risk factor control in concordance with clinical guidelines, respectively. Net savings resulted from reduced costs to treat diabetes complications (¥38, ¥67, ¥124, ¥141, ¥161, and ¥212 billion) and excess treatment costs alongside stepwise management improvements (¥4, ¥32, ¥65, ¥69, ¥86, and ¥107 billion). Per-capita life expectancy was increased by 0.26, 0.68, 1.33, 1.47, 1.69, and 3.21 years, respectively. CONCLUSIONS: Improved T2D management strategies can help to decrease the financial burden of the disease and increase life expectancy of individuals with T2D.

Cost-effectiveness of basal insulin from a US health system perspective: comparative analyses of detemir, glargine, and NPH.

The purpose of this study was to compare in clinical and economic terms the long-acting insulin analogue detemir with intermediate-acting Neutral Protamine Hagedorn (NPH) insulin and with long-acting insulin glargine. Investigators used the validated Center for Outcomes Research (CORE) Diabetes Model to project clinical and cost outcomes over a 35-year base case time horizon; outcome data were extracted directly from randomized, controlled trials designed to compare detemir with NPH and with insulin glargine. Modeled patient characteristics were derived from corresponding trials, and simulations incorporated published quality-of-life utilities with cost data obtained from a Medicare perspective. Detemir, when compared with NPH, increased quality-adjusted life expectancy by 0.698 quality-adjusted life-years (QALYs). Lifetime direct medical costs were increased by 10,451 dollars per patient, although indirect costs were reduced by 4688 dollars. On the basis of direct costs, the cost per QALY gained with detemir was 14,974 dollars. In comparison with glargine, detemir increased quality-adjusted life expectancy by 0.063 QALYs, reduced direct medical costs by 2072 dollars per patient, and decreased indirect costs by 3103 dollars (dominant). Reductions in diabetes-related comorbidities were also associated with detemir in both instances, most notably in the complications of retinopathy and nephropathy. Relative reductions in rates of complications were greatest in the comparison of detemir with NPH. Results were most sensitive to variation in hemoglobin A1c (HbA1c) levels. However, variation among any of the key assumptions, including HbA1c, did not alter the relative results. Detemir represents an attractive clinical and economic intervention in the US health care setting compared with both NPH insulin and insulin glargine.

Treating diabetes to accepted standards of care: a 10-year projection of the estimated economic and health impact in patients with type 1 and type 2 diabetes mellitus in the United States.

OBJECTIVE: The aim of this study was to investigate the health-economic impact of maintaining glycosylated hemoglobin (HbA(1c)) values in all US patients with currently uncontrolled type 1 or type 2 diabetes mellitus at the American Diabetes Association (ADA) standard of 7.0% and the American Association of Clinical Endocrinologists (AACE) target of 6.5% compared with maintenance at current population-based values. METHODS: The CORE-Center for Outcomes Research Diabetes Model was used to predict costs and outcomes for patients with uncontrolled type 1 and type 2 diabetes who remain at established population mean HbA(1c) values in comparison with those for patients who maintain the standard value of 7.0% or the target value of 6.5%. The analysis was run from a societal perspective over a 10-year time horizon. The costs of treating complications and medication costs were retrieved from published sources. Costs and clinical outcomes were discounted at 3% per annum. Sensitivity analyses were performed on the discount rate and time horizon. RESULTS: This analysis found that maintaining HbA(1c) at the ADA standard value of 7.0% and the AACE target value of 6.5% in patients with uncontrolled type 1 and type 2 diabetes could achieve total direct medical cost savings of nearly 35 US dollars and 50 billion US dollars , respectively, over 10 years. When indirect cost savings were included, the total savings increased to between nearly 50 billion US dollars and 72 billion US dollars for these respective HbA(1c) targets, corresponding to 4% and 6% of the total annual US health care costs of 1.3 trillion US dollars. Reduced savings were observed with a higher discount rate and shorter time horizon, but savings increased as the time horizon became longer. These cost savings must be weighed against the cost of reaching the HbA(1c) goals and the likelihood of achieving the clinical objectives. CONCLUSIONS: Efficient targeting of financial resources toward the goal of lowering HbA(1c) in line with published guidelines could lead to financial savings in the range from nearly 35 billion US dollars to 72 billion US dollars over the next 10 years.

Long-term clinical and cost outcomes of treatment with biphasic insulin aspart 30/70 versus insulin glargine in insulin naïve type 2 diabetes patients: cost-effectiveness analysis in the UK setting.

OBJECTIVES: To evaluate the long-term clinical and cost outcomes associated with biphasic insulin aspart 30/70 (BIAsp 30/70, premixed 30% soluble and 70% protaminated insulin aspart in one injection) compared to insulin glargine treatment in insulin-naïve type 2 diabetes patients failing oral antidiabetic agents in the UK, based on findings recently reported from the INITIATE clinical trial. METHODS: The CORE Diabetes Model, a published, peer-reviewed and validated model of diabetes, was used to evaluate life expectancy, quality-adjusted life expectancy, cumulative incidence of complications and direct medical costs over patient lifetimes. The model simulates the range of diabetic complications and disease progression within a series of sub-models (cardiovascular disease, neuropathy, renal and eye disease) based on published data. Baseline cohort characteristics (54.5% male, mean age 52.45 years, mean diabetes duration 9 years, mean HbA(1c) 9.77%) and treatment effects were based on INITIATE. Costs were derived from published UK sources. The analysis was run over a 35-year time horizon (patient lifetime) from a third party payer perspective. Costs and clinical benefits were discounted at 3.5% per annum. Sensitivity analyses were performed. RESULTS: BIAsp 30/70 was associated with projected improvements in discounted life expectancy (0.19 +/- 0.20 years) and quality-adjusted life expectancy (0.19 +/- 0.14 quality-adjusted life years [QALYs]), as well as a reduced incidence of retinopathy and nephropathy complications, versus glargine. Total lifetime direct costs were 1319 pounds higher with BIAsp 30/70 than with glargine leading to an incremental cost-effectiveness ratio of 6951 pounds per QALY gained. CONCLUSIONS: This study is the first to address the long-term health economic implications of treating type 2 diabetes patients failing oral anti-diabetics with a biphasic insulin mix versus long-acting insulin. Our projections indicate that improved HbA1c levels with BIAsp 30/70 treatment are associated with improvements in life expectancy and quality-adjusted life expectancy, and that BIAsp 30/70 represents excellent value for money compared to insulin glargine in the UK.

Insulin degludec early clinical experience: does the promise from the clinical trials translate into clinical practice--a case-based evaluation.

BACKGROUND: Clinical experience of patients is an additional source of information that can inform prescribing decisions for new therapies in practice. In diabetes, for example, patients with recurrent hypoglycemia may be excluded from trials conducted for regulatory purposes. Using insulin degludec (IDeg), a new basal insulin with an ultra-long duration of action as an example, an interim analysis is presented describing whether the decision to prescribe IDeg to patients experiencing treatment-limiting problems on their existing insulin regimes represented good clinical and economic value. METHODS: Records from the first 51 consecutive patients with diabetes (35 type 1 [T1D] and 16 type 2 [T2D]) switching to insulin degludec from either insulin glargine (IGlar) or insulin detemir (IDet), mostly due to problems with hypoglycemia (39/51, 76.5%), were reviewed at up to 37 weeks. Patients indicated frequency of hypoglycemia and completed a disease-specific questionnaire reporting six measures of confidence and treatment satisfaction. For the largest group of exposed patents, the T1D module of the IMS Core Diabetes Model (CDM) was used to evaluate the cost-effectiveness of the treatment decision. FINDINGS: HbA1c decreased by 0.5 ± 0.3% points and 0.7 ± 0.3% points for T1D and T2D, respectively. Hypoglycemic events decreased by >90%. Combined mean scores were ≥ 3.7 (1 = much worse, 3 = no change, 5 = much improved) for all six satisfaction and confidence items. In T1D, the treatment decision was highly cost-effective in the CDM lifetime analysis. Even when excluding benefits beyond hypoglycemia reduction, predicted cost per quality-adjusted life-year for IDeg vs IGlar/IDet was £10,754. INTERPRETATION: These data illustrate the complementary nature of clinical trial and practice data when evaluating the value of therapeutic innovations in diabetes care. There were reductions in patient-reported hypoglycemia, reduced HbA1c, and improved treatment satisfaction in relation to the decision to prescribe IDeg. Initial health economic evaluation suggested that the decision to prescribe IDeg in this phenotypic group of T1D patients represented good value for money.

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.

The CORE Diabetes Model: Projecting long-term clinical outcomes, costs and cost-effectiveness of interventions in diabetes mellitus (types 1 and 2) to support clinical and reimbursement decision-making.

OBJECTIVES: We have developed an Internet-based, interactive computer model to determine the long-term health outcomes and economic consequences of implementing different treatment policies or interventions in type 1 and type 2 diabetes mellitus. The model projects outcomes for populations, taking into account baseline cohort characteristics and past history of complications, current and future diabetes management and concomitant medications, screening strategies and changes in physiological parameters over time. The development of complications, life expectancy, quality-adjusted life expectancy and total costs within populations can be calculated. METHODS: The model is based on a series of sub-models that simulate important complications of diabetes (cardiovascular disease, eye disease, hypoglycaemia, nephropathy, neuropathy, foot ulcer, amputation, stroke, ketoacidosis, lactic acidosis and mortality). Each sub-model is a Markov model using Monte Carlo simulation incorporating time, state, time-in state, and diabetes type-dependent probabilities derived from published sources. Analyses can be performed on cohorts with type 1 or type 2 diabetes. Cohorts, defined in terms of age, gender, baseline risk factors and pre-existing complications, can be modified or new cohorts defined by the user. Economic and clinical data in the model can be edited, thus ensuring adaptability by allowing the inclusion of new data as they become available; creation of country- or provider-specific versions of the model; and allowing the investigation of new hypotheses. CONCLUSIONS: The CORE Diabetes Model allows the calculation of long-term outcomes, based on the best data currently available. Diabetes management strategies can be compared in different patient populations in a variety of realistic clinical settings, allowing the identification of efficient diabetes management strategies.

Validation of the CORE Diabetes Model against epidemiological and clinical studies.

OBJECTIVES: The aim of this study was to assess the validity of the CORE Diabetes Model by comparing results from model simulations with observed outcomes from published epidemiological and clinical studies in type 1 and type 2 diabetes. METHODS: A total of 66 second- (internal) and third- (external) order validation analyses were performed across a range of complications and outcomes simulated by the CORE Diabetes Model (amputation, cataract, hypoglycaemia, ketoacidosis, macular oedema, myocardial infarction, nephropathy, neuropathy, retinopathy, stroke and mortality). Published studies were reproduced in the model by recreating cohorts in terms of demographics, baseline risk factors and complications, treatment patterns and patient management strategies, and simulating the progress of the cohort to an equivalent time horizon. RESULTS: Correlation analysis on results from 66 validation simulations produced an R2 value of 0.9224 (perfect fit = 1). A correlation plot of published study data versus values simulated by the CORE Diabetes Model had a trend line with a gradient of 1.0187 (perfect fit = 1). Validation analyses in type 1 and type 2 diabetes were associated with R2 values of 0.9778 and 0.8861 respectively. Correlation of second-order validation analyses (model predictions versus observed outcomes in studies used to construct the model) produced an R2 value of 0.9574, and the value for third-order analyses (model predictions versus observed outcomes in studies not used to construct the model) was 0.9023. CONCLUSIONS: The CORE Diabetes Model provides an accurate representation of patient outcomes when compared to 66 studies of diabetes and its complications. Model flexibility ensures it can be used to compare diabetes management strategies in different cohorts across a variety of clinical settings.

Self-monitoring of blood glucose (SMBG) in patients with type 2 diabetes on oral anti-diabetes drugs: cost-effectiveness in France, Germany, Italy, and Spain.

OBJECTIVE: Stakeholders in Europe remain interested in assessments of country-specific value of self-monitoring of blood glucose (SMBG) for patients with type 2 diabetes treated with oral anti-diabetes drugs (OADs). This study used the IMS-CORE Diabetes Model to project the long-term (40-year) cost-effectiveness of SMBG at once, twice, or three times per day (vs. no SMBG) for this population from national reimbursement system perspectives in France, Germany, Italy, and Spain. METHODS: SMBG input costs (strips, lancets, meters, nurse training) were supplied by LifeScan in 2007 euro values and applied as appropriate for each country's reimbursement policy. Cohort characteristics and assumed Hb(A1c) effects came from a US Kaiser Permanente longitudinal analysis of new SMBG users. Country-specific estimations for use of screening programs and several concomitant medications, as well as mortality rates were used. Country-specific complication costs from published sources were inflated to 2007 euro. Base case outcomes were discounted at 3% per annum for France, Germany, and Italy; 6% for Spain. Sensitivity analyses varied time horizon and discount rates for each country. They also included a -0.036 dis-utility for SMBG in year 1. MAIN OUTCOME MEASURES: Primary outcomes included total direct costs, gains in quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) over 40 years. RESULTS: ICERs were largest in France (with meter costs included), and in Italy (with highest reimbursed costs for strips/lancets). ICERs for SMBG once, twice, and three times per day were 12,114 euros, 6282 euros, and 7958 euros (respectively) in France; and 12,694 euros, 11,934 euros, and 15,368 euros in Italy. ICERs for SMBG once or twice per day were <2000 euros in Germany and <4000 euros in Spain. ICERs for SMBG three times per day were <6000 euros/QALY in both countries. Results were most sensitive to the 5-year time horizon, although ICERs for SMBG once per day were below 50,000 euros/QALY in all countries but Italy (ICER = 77,064 euros). Five-year ICERs for SMBG twice per day were below 40,000 euros/QALY for all four countries, and those for SMBG three times per day were below 45,000 euros/QALY. With the SMBG dis-utility, ICERs increased modestly (321 euros- 2264 euros/QALY) in all scenarios except SMBG once per day in France (9578 euros increase) and Italy (5979 euros increase). Study limitations include the use of relatively short-term data from a single US observational study for SMBG clinical effects, unknown levels of patient adherence, and assumptions regarding the duration of clinical effects. CONCLUSIONS: With cost assumptions reflecting current reimbursement levels in France, Germany, Italy, and Spain, SMBG was found to be cost-effective across a 40-year time horizon, with all base case ICERs <16,000/QALY. This study adds to the literature on the country-specific, long-term value of SMBG for type 2 diabetes patients treated with OADs. Under current model assumptions, variations in cost-effectiveness results stemmed primarily from payer reimbursement practices for SMBG within each country.

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.