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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.

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.

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

ABSTRACT Objectives: The aim of this study was to evaluate the long-term clinical and economic outcomes associated with exenatide or insulin glargine, added to oral therapy in individuals with type 2 diabetes inadequately controlled with combination oral agents in the UK setting. Methods: A published and validated computer simulation model of diabetes was used to project long-term complications, life expectancy, quality-adjusted life expectancy and direct medical costs. Probabilities of diabetes-related complications were derived from published sources. Treatment effects and patient characteristics were extracted from a recent randomised controlled trial comparing exenatide with insulin glargine. Simulations incorporated published quality of life utilities and UK-specific costs from 2004. Pharmacy costs for exenatide were based on 20, 40, 60, 80 and 100% of the US value (as no price for the UK was available at the time of analysis). Future costs and clinical benefits were discounted at 3.5% annually. Sensitivity analyses were performed. Results: In the base–case analysis exenatide was associated with improvements in life expectancy of 0.057 years and in quality-adjusted life expectancy of 0.442 quality-adjusted life years (QALYs) versus insulin glargine. Long-term projections demonstrated that exenatide was associated with a lower cumulative incidence of most cardiovascular disease (CVD) complications and CVD-related death than insulin glargine. Using the range of cost values, evaluation results showed that exenatide is likely to fall in a range between dominant (cost and life saving) at 20% of the US price and cost-effective (with an ICER of £22 420 per QALY gained) at 100% of the US price, versus insulin glargine. Conclusions: Based on the findings of a recent clinical trial, long-term projections indicated that exenatide is likely to be associated with improvement in life expectancy and quality-adjusted life expectancy compared to insulin glargine. The results from this modelling analysis suggest that that exenatide is likely to represent good value for money by generally accepted standards in the UK setting in individuals with type 2 diabetes inadequately controlled on oral therapy.

Estimating the clinical benefits of vaccinating boys and girls against HPV-related diseases in Europe

BackgroundHPV is related to a number of cancer types, causing a considerable burden in both genders in Europe. Female vaccination programs can substantially reduce the incidence of HPV-related diseases in women and, to some extent, men through herd immunity. The objective was to estimate the incremental benefit of vaccinating boys and girls using the quadrivalent HPV vaccine in Europe versus girls-only vaccination. Incremental benefits in terms of reduction in the incidence of HPV 6, 11, 16 and 18-related diseases (including cervical, vaginal, vulvar, anal, penile, and head and neck carcinomas and genital warts) were assessed.MethodsThe analysis was performed using a model constructed in Microsoft®Excel, based on a previously-published dynamic transmission model of HPV vaccination and published European epidemiological data on incidence of HPV-related diseases. The incremental benefits of vaccinating 12-year old girls and boys versus girls-only vaccination was assessed (70% vaccine coverage were assumed for both). Sensitivity analyses around vaccine coverage and duration of protection were performed.ResultsCompared with screening alone, girls-only vaccination led to 84% reduction in HPV 16/18-related carcinomas in females and a 61% reduction in males. Vaccination of girls and boys led to a 90% reduction in HPV 16/18-related carcinomas in females and 86% reduction in males versus screening alone. Relative to a girls-only program, vaccination of girls and boys led to a reduction in female and male HPV-related carcinomas of 40% and 65%, respectively and a reduction in the incidence of HPV 6/11-related genital warts of 58% for females and 71% for males versus girls-only vaccination.ConclusionsIn Europe, the vaccination of 12-year old boys and girls against HPV 6, 11, 16 and 18 would be associated with substantial additional clinical benefits in terms of reduced incidence of HPV-related genital warts and carcinomas versus girls-only vaccination. The incremental benefits of adding boys vaccination are highly dependent on coverage in girls. Therefore, further analyses should be performed taking into account the country-specific situation. In addition to clinical benefits, substantial economic benefits are also anticipated and warrant further investigation as do the social and ethical implications of including boys in vaccination programs.

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

ABSTRACT Objective: The aim of this review is to summarize published data (based on a search of Medline sources, 1993–October 2003) from the last 10 years on the costs of stroke. With the recent encouraging evidence of interventions that reduce the incidence of stroke, the primary focus is on incidence-based cost of stroke studies to identify important factors for future cost-effectiveness analyses on stroke interventions. Findings: Lifetime costs per patient were in the range USD 11 787 for ‘unclassified’ stroke in Australia to USD 3 035 671 in stroke patients with untreated non-rheumatic atrial fibrillation in a UK setting (costs inflated to 2003 values). For the lifetime costs of ischemic stroke only, the range narrowed to USD 41 257 in Australia and USD 104 629 in the UK. These data confirm that stroke management is associated with a vast economic burden. No correlation of lifetime cost of stroke with specific cost components or time horizon was identified. The cost of stroke is influenced by severity (more severe strokes cost more due to extended hospitalization), age (costs were greater in younger stroke patients) and gender (direct costs were greater for women, but indirect costs were greater in men). Conclusion: Conducting research according to methodological consensus would markedly improve the quality of data from future studies of stroke and support identification of the main cost drivers in different country-specific settings.

Estimating the Long-Term Cost-Effectiveness of Exenatide in the United States: An Adjunctive Treatment for Type 2 Diabetes Mellitus

OBJECTIVES This analysis provides an early estimate of the cost-effectiveness of adjunctive exenatide in treating type 2 diabetes mellitus in the United States. Data from pivotal phase III 30-week clinical trials and 52 weeks of their subsequent open-label extension studies (i.e., 82 weeks total) were used to project the effects of 30 years of adjunctive exenatide treatment. METHODS This analysis utilized a published and validated Markov model incorporating Monte Carlo simulation with tracker variables to estimate the clinical and cost outcomes of adding exenatide to a background of metformin and/or sulfonylurea treatment, with the effects of 30 years of adjunctive exenatide treatment (projected from data from 82 weeks of exenatide treatment) compared with no additional treatment beyond metformin and/or a sulfonylurea. Sensitivity analyses were performed on key clinical assumptions, discount rates, and shorter time horizons. RESULTS The base-case scenario (30 years of exenatide) yielded an incremental cost-effectiveness ratio (ICER) of

The cost-effectiveness of irbesartan in the treatment of hypertensive patients with type 2 diabetic nephropathy

35,571. We found that shortening the time horizons and removing the lipid effects of exenatide had the greatest negative impact on ICERs when performing sensitivity analysis. CONCLUSIONS Our analysis demonstrated that exenatide used for 20 or 30 years compared with no additional treatment beyond metformin and/or a sulfonylurea is cost-effective in the adjunctive treatment of type 2 diabetes with an ICER less than

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

50,000 per life-year gained. Sensitivity analyses suggest that, in addition to sustained reduction in HbA(1c), the added clinical effects of improved lipid values, systolic blood pressure, and reduced body mass index all positively contributed to the cost-effectiveness of exenatide.