Wj Valentine

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

SUMMARY Objectives: We have developed an Internet-based, interactive computer model to determine the longterm 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.

Cost-Effectiveness of Intensified Versus Conventional Multifactorial Intervention in Type 2 Diabetes Results and projections from the Steno-2 study

OBJECTIVE—To assess the cost-effectiveness of intensive versus conventional therapy for 8 years as applied in the Steno-2 study in patients with type 2 diabetes and microalbuminuria. RESEARCH DESIGN AND METHODS—A Markov model was developed to incorporate event and risk data from Steno-2 and account Danish-specific costs to project life expectancy, quality-adjusted life expectancy (QALE), and lifetime direct medical costs expressed in year 2005 Euros. Clinical and cost outcomes were projected over patient lifetimes and discounted at 3% annually. Sensitivity analyses were performed. RESULTS—Intensive treatment was associated with increased life expectancy, QALE, and lifetime costs compared with conventional treatment. Mean ± SD undiscounted life expectancy was 18.1 ± 7.9 years with intensive treatment and 16.2 ± 7.3 years with conventional treatment (difference 1.9 years). Discounted life expectancy was 13.4 ± 4.8 years with intensive treatment and 12.4 ± 4.5 years with conventional treatment. Lifetime costs (discounted) for intensive and conventional treatment were €45,521 ± 19,697 and €41,319 ± 27,500, respectively (difference €4,202). Increased costs with intensive treatment were due to increased pharmacy and consultation costs. Discounted QALE was 1.66 quality-adjusted life-years (QALYs) higher for intensive (10.2 ± 3.6 QALYs) versus conventional (8.6 ± 2.7 QALYs) treatment, resulting in an incremental cost-effectiveness ratio of €2,538 per QALY gained. This is considered a conservative estimate because accounting prescription of generic drugs and capturing indirect costs would further favor intensified therapy. CONCLUSIONS—From a health care payer perspective in Denmark, intensive therapy was more cost-effective than conventional treatment. Assuming that patients in both arms were treated in a primary care setting, intensive therapy became dominant (cost- and lifesaving).

Intensive lifestyle changes or metformin in patients with impaired glucose tolerance: modeling the long-term health economic implications of the diabetes prevention program in Australia, France, Germany, Switzerland, and the United Kingdom

BACKGROUND In the Diabetes Prevention Program (DPP), interventions with metformin (plus standard lifestyle advice) or intensive lifestyle changes (ILC) reduced the risk of developing type 2 diabetes mellitus (DM) by 31% and 58%, respectively, versus control (standard lifestyle advice only) in patients with impaired glucose tolerance (IGT). OBJECTIVE The goal of this study was to establish whether implementing the active treatments used in the DPP would be cost-effective in Australia, France, Germany, Switzerland, and the United Kingdom. METHODS A Markov model simulated 3 states-IGT, type 2 DM, and deceased-using probabilities from the DPP and published data. Country-specific direct costs were used throughout. RESULTS Assuming only within-trial effects and costs of interventions, both metformin and ILC improved life expectancy versus control. Mean improvements in nondiscounted life expectancy were 0.11 and 0.22 years for metformin and ILC, respectively. Both interventions were associated with cost savings versus control in all countries except the United Kingdom, where a small increase in costs was observed in both intervention arms. When a lifetime effect of interventions was assumed, incremental improvements in life expectancy were 0.35 and 0.90 years for metformin and ILC, respectively. Results were sensitive to probabilities of developing type 2 DM, the projected long-term duration of effect of interventions after the 3-year trial period, the relative risk of mortality for type 2 DM compared with IGT, and the costs of implementing the interventions. CONCLUSIONS Based on probabilities from the DPP and published data, in this model analysis, incorporation of the DPP interventions into clinical practice in 5 developed countries was projected to lead to an increase in DM-free years of life, improvements in life expectancy, and either cost savings or minor increases in costs compared with standard lifestyle advice in a population with IGT. Thus, financial constraints should not prevent the implementation of DM prevention programs.

Health-economic comparison of continuous subcutaneous insulin infusion with multiple daily injection for the treatment of Type 1 diabetes in the UK.

Objectives  The aim of this study was to project the long‐term costs and outcomes of continuous subcutaneous insulin infusion (CSII) compared with multiple daily injections (MDI) in patients with Type 1 diabetes in the UK.

Review of the cost of diabetes complications in Australia, Canada, France, Germany, Italy and Spain

ABSTRACT Objectives: To provide a comprehensive source document on previously published cost data for diabetic complications in Australia, Canada, France, Germany, Italy and Spain for use in a peer-reviewed, validated diabetes model. Methods: A search for published cost of diabetes complications data was performed in peer-reviewed journals listed in PubMed and health economic conference proceedings from 1994 to March 2005. Where country specific data were not available, we referred to government websites and local cost experts. All costs were inflated to 2003 Euros (€). Major complication costs are presented. Results: First year costs of non-fatal myocardial infarction varied between €19 277 in Spain and €12 292 in Australia. In subsequent years of treatment, this range was €1226 (France) to €203 (Australia). Angina costs were similar across all four countries: €1716 in Australia; €2218 in Canada; €2613 in France; €3342 in Germany; €2297 in Italy; and €2207 in Spain. Event costs of non-fatal stroke were higher in Canada (€23 173) than in other countries (Australia €13 443; France €11 754; Germany €19 399; Italy €6583; Spain €4638). Event costs of end-stage renal disease varied depending on the type of dialysis: in Australia (€17 188–27 552); Canada (€33 811–58 159); France (€24 608–56 487); Germany (€46 296–68 175); Italy (€43 075–56 717); and Spain (€28 370–32 706). Lower extremity amputation costs were: €18 547 (Australia); €17 130 (Canada); €31 998 (France); €22 096 (Germany); €10 177 (Italy); and €14 787 (Spain). Conclusions: Overall, our search showed costs are well documented in Australia, Canada, France and Germany, but revealed a paucity of data for Spain and Italy. Spanish costs, collected by contacting local experts and from government reports, generally appeared to be lower for treating cardiovascular complications than in other countries. Italian costs reported in the literature were primarily hospitalization costs derived from diagnosis-related groups, and therefore likely to misrepresent the cost of specific complications. Additional research is required to document complication costs in Spain and Italy. Australian and German values were collected primarily by referring to diagnostic related group (DRG) tariffs and, as a result, there may be a need for future economic evaluations measuring the accuracy of the costs and resource utilization in the reported values. These cost data are essential to create models of diabetes that are able to accurately simulate the cumulative costs associated with the progression of the disease and its complications.

A health economic analysis of screening and optimal treatment of nephropathy in patients with type 2 diabetes and hypertension in the USA

BACKGROUND Nephropathy is an indicator of end-organ damage and is a strong predictor of an increased risk of cardiovascular disease and death in patients with diabetes. Screening can lead to early identification and treatment, both of which incur costs. However, identification and treatment may slow or prevent progression to a more expensive stage of the disease and thus may save money. We assessed the health economic impact of screening for nephropathy (microalbuminuria and overt nephropathy) followed by optimal renoprotective-based antihypertensive therapy in a US setting. METHODS A Markov model simulated the lifetime impact of screening with semi-quantitative urine dipsticks in a primary care setting of hypertensive patients with type 2 diabetes and subsequent treatment with irbesartan 300 mg in patients identified as having nephropathy. Progression from no nephropathy to end-stage renal disease (ESRD) was simulated. Probabilities, utilities, medication and ESRD treatment costs came from published sources. Clinical outcomes and direct medical costs were projected. Second order Monte Carlo simulation was used to account for uncertainty in multiple parameters. Annual discount rates of 3% were used where appropriate. RESULTS Screening, followed by optimized treatment, led to a 44% reduction in the cumulative incidence of ESRD and improvements in non-discounted life expectancy of 0.25 +/- 0.22 years/patient (mean +/- SD). Quality-adjusted life expectancy was improved by 0.18 +/- 0.15 quality-adjusted life years (QALYs)/patient and direct costs increased by

Exenatide versus insulin glargine in patients with type 2 diabetes in the UK : a model of long-term clinical and cost outcomes

244 +/- 3499/patient. The incremental cost-effectiveness ratio was

Multigene assays and molecular markers in breast cancer: systematic review of health economic analyses

20 011 per QALY gained for screening and optimized treatment versus no screening. There was a 77% probability that screening and optimized therapy would be considered cost effective with a willingness to pay a threshold of

Overview of costs of stroke from published, incidence-based studies spanning 16 industrialized countries.

50 000. CONCLUSION In patients with type 2 diabetes and hypertension, screening for nephropathy and treatment with a renoprotective-based antihypertensive agent was projected to improve patient outcomes and represent excellent value in a US setting.