M Lamotte

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 analysis of clopidogrel versus aspirin in patients with atherothrombosis based on the CAPRIE trial

SUMMARY Clopidogrel has been shown to reduce the secondary risk of ischaemic events in vascular disease compared to aspirin. This article compares the economics of the two drugs for this condition, by providing an incremental cost-effectiveness ratio (iCER) of clopidogrel versus aspirin, using Belgium as a case setting. A 2 year Markov model, in which patients with vascular disease were assumed to receive either clopidogrel or aspirin, was developed from a healthcare payers perspective. Survival data were based on the Saskatchewan Health database. Costs included treatment and adverse events. Cost-effectiveness was expressed as the cost per life year gained (LYG). The iCER of clopidogrel versus aspirin was €13,390/LYG (95% CI: €6,990; €26,470). The robustness of these results was shown by univariate and probabilistic sensitivity analyses. This analysis shows that clopidogrel is cost-effective for the secondary prevention of ischaemic events in the Belgian setting.

A multi-country health economic evaluation of highly concentrated n-3 polyunsaturated fatty acids in secondary prevention after myocardial infarction

AbstractBackground: Patients who survive an acute myocardial infarction (MI) are at an increased risk of subsequent major cardiovascular events and (often sudden) cardiac death. The use of highly concentrated and purified omega-3 polyunsaturated fatty acids (n-3 PUFAs), in addition to standard secondary prevention after MI, results in a significant reduction in the risk of sudden death versus no n-3 PUFAs. This study assessed the cost effectiveness of adding n-3 PUFAs to the current secondary prevention treatment versus standard prevention alone after acute MI in five countries: Australia, Belgium, Canada, Germany and Poland. Methods: Based on the clinical outcomes of GISSI-P (Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico — Prevenzione) [MI, stroke, revascularisation rate and mortality], a decision model was built in DataPro™. The implications of adding n-3 PUFAs to standard treatment in patients aged 59 years with a recent history of MI were analysed from the healthcare payer’s perspective. The time horizon was 3.5 years (identical to GISSI-Prevenzione) but the effects on life expectancy through avoidance of cardiac events were calculated lifelong. Event costs were based on literature data. Life expectancy data for survivors of cardiac disease were taken from the Saskatchewan database and then adjusted by country. Results are expressed as extra cost (€) per life-year gained (LYG). Annual discounting of 5% was applied to health effects and costs. Results: Treatment with highly concentrated n-3 PUFAs yielded between 0.261 (Poland) and 0.284 (Australia) LYG, at an additional cost of €787 (Canada) to €1439 (Belgium). The ICER varied between €2788 (Canada) and €5097 (Belgium) per LYG. Sensitivity analyses on effectiveness, cost of complications and discounting proved the robustness of the results. A second-order Monte Carlo simulation based on the 95% confidence intervals obtained from GISSI-P suggests that highly concentrated n-3 PUFAs are cost effective in 93% of simulations in Poland and in >98% of simulations in the other countries, assuming the country-specific societal willingness-to-pay threshold. Total costs were considerably increased by including healthcare costs incurred during the remaining life-years, but this had no impact on the ICER-based treatment recommendation. Conclusions: Adding highly concentrated n-3 PUFAs to standard treatment in the secondary prevention of MI appears to be cost effective versus standard treatment alone in the five countries studied.

A Multi-Country Economic Evaluation of Low-Dose Aspirin in the Primary Prevention of Cardiovascular Disease

BackgroundLow-dose aspirin (acetylsalicylic acid) is standard care in patients with a history of cardiovascular disease (CVD). The use of low-dose aspirin in primary prevention is not yet fully established, although meta-analyses and US and European guidelines support its use in people at increased risk of CVD. The primary objective of this study was to assess the economic consequences of the use of low-dose aspirin in the primary prevention of CVD in four European countries (UK, Germany, Spain and Italy).MethodsBased on results (benefits and harms) reported in meta-analyses, a state-transition model was developed to predict the cost effectiveness of low-dose aspirin in the primary prevention of CVD. The model consists of five health states: no history of CVD, history of stroke, history of myocardial infarction (MI), history of stroke and MI, and death. A 10-year time horizon and 1-year cycles were used. Secondary prevention data were derived from the aspirin arm of the CAPRIE (Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events) study.Direct costs from the public healthcare payer’s perspective were used (€, 2003 values). Effects were expressed in life-years (LY) and QALYs gained. Quality weights were obtained from published data.Country-specific discounting was applied on effects and costs (3.5% for the UK, 5% for Germany and 3% for Spain and Italy). Univariate sensitivity analysis and Monte Carlo simulation were performed to assess uncertainty in the results.ResultsFor patients with an annual risk of coronary heart disease (CHD) of 1.5%, the model resulted in 10-year savings with low-dose aspirin of on average €201 (95% CI 81, 331), €281 (95% CI 141, 422), €797 (95% CI 301, 1331) and €427 (95% CI 122, 731) per patient in the UK, Germany, Spain and Italy, respectively. Average total cost was almost 3- to 4-fold higher in Spain and Italy than in the UK and Germany. Savings (non-significant) start in the first year of treatment in all countries.Sensitivity analyses on cost of complications, utility, discounting, stroke rate and gastrointestinal bleeding rate showed the robustness of the results. From an annual risk of CHD of 0.236% for the UK, 0.324% for Germany, 0.244% for Spain and 0.560% for Italy, low-dose aspirin was cost saving compared with placebo. Monte Carlo analysis showed aspirin dominance in about 97% of cases for the three studied annual risks of CHD (0.6%, 1.0% and 1.5%) in the UK, Germany and Spain. In Italy, aspirin dominance in >95% of cases was seen at annual risks of 1% and 1.5%.ConclusionsAdministering low-dose aspirin to patients with an annual risk of CHD of ≥1% appears to be significantly cost saving from the healthcare payer’s perspective in all countries analysed. Sensitivity analyses (CHD risk and bleedings) suggested the results were robust.

An economic evaluation of the Irbesartan in Diabetic Nephropathy Trial (IDNT) in a UK setting

There are substantial healthcare costs associated with the provision of renal replacement therapy. Patients with diabetes mellitus are the largest and fastest growing group developing end-stage renal disease (ESRD) in the United Kingdom (UK). Treatment leading to a slowing of progression to ESRD in diabetic patients could lead to considerable cost savings. Using treatment-specific probabilities derived from the Irbesartan in Diabetic Nephropathy Trial (IDNT), the cost effectiveness of treating patients with hypertension, type II diabetes and nephropathy with irbesartan, amlodipine or control was calculated using a Markov model. UK-specific ESRD-related data were retrieved from published sources to reflect local management practices, ESRD outcomes and costs. Mean 10-year costs and changes in life expectancy due to ESRD delayed or avoided were calculated. Future costs and clinical benefits were discounted at 6.0 and 1.5% per annum and extensive sensitivity analyses were performed. Delay in the onset of ESRD with irbesartan led to cost savings of £5125 and £2919/patient and improvements in projected discounted life expectancy of 0.07 and 0.21 years over 10 years vs amlodipine and control, respectively. The costs of treatment of ESRD were the main contributor to the total costs. The cost of trial medications had only a minor impact. These results were robust in a wide range of plausible assumptions. Given that the IDNT efficacy results could be translated to a UK setting, treating patients with hypertension, type II diabetes and overt nephropathy with irbesartan was cost saving over a 10-year period compared to amlodipine and control.

The Cost Utility of Autologous Chondrocytes Implantation Using ChondroCelect in Symptomatic Knee Cartilage Lesions in Belgium

AbstractBackground: Knee cartilage lesions increase the risk of developing osteoarthritis (OA), and may eventually result in a total knee replacement (TKR). There is currently no consensus on the optimal treatment of cartilage lesions. ChondroCelect® (CC) is a cell-based therapy approved for use in autologous chondrocytes implantation (ACI) to treat symptomatic cartilage defects of the femoral condyle. Its capacity to safely restore good-quality cartilage was demonstrated in a randomized controlled trial (RCT) versus the surgical procedure microfracture (MFX). Objective: This study investigated the cost utility of CC used in ACI compared with MFX to treat symptomatic knee cartilage lesions in Belgium. Methods: A decision tree model comparing CC with MFX over a 40-year horizon was developed in TreeAge Pro™. The key timepoints of the model were (i) clinical assessment 5 years after initial intervention (success or no success, with or without re-operation); (ii) development of OA at 15 years (yes/no); (iii) need for TKR at 20 years (yes/no); and (iv) need for prosthesis revision at 35 years (yes/no). Clinical data provided by the RCT of CC versus MFX were the clinical success (response) rate based on the Knee injury and Osteoarthritis Outcome Score (KOOS) at 36 months (82.9% vs 62.0%; p = 0.048) and the proportion of good structural repair/presence of hyaline cartilage based on International Cartilage Repair Society (ICRS II) visual item at 12 months (44.9% vs 23.2%; p= 0.023). Utility scores by surgery outcome were derived from the SF-36 questionnaire responses collected in the RCT. Conservative assumptions related to the incidences of OA, TKR and prosthesis revision relied on a literature search. A patient chart review (n = 82) provided follow-up costs by surgery outcome. National tariffs were applied to direct medical resources used (healthcare payer perspective, year 2008 costs). Annual discounting was applied to costs (3%) and effects (1.5%) as recommended by the Belgian pharmacoeconomic guidelines. Results: The incremental cost per QALY gained for CC compared with MFX was €16 229, with a difference in costs of €20 802 and 1.282 QALYs gained. Sensitivity analyses indicated that the key model drivers were the proportion of patients with hyaline cartilage and the correlation between hyaline cartilage formation and later avoidance of OA. Probabilistic sensitivity analyses showed robustness of the results, with 80% of the simulations below the usual UK National Institute for Health and Clinical Excellence (NICE) threshold of €22 000 per QALY. Conclusions: Assuming a good correlation between high-quality cartilage repair and avoidance of OA at a later stage, the benefits of the cell therapy CC over MFX in terms of QALYs gained and OA-related costs avoided appear real. Further research is required to explore long-term effects of cartilage repair and reduce uncertainty on quality of life of patients with OA before and after joint replacement.

Economic burden associated with the management of cervical cancer, cervical dysplasia and genital warts in Belgium

Abstract Objective: Human papillomavirus (HPV) infections can lead to cervical intraepithelial neoplasia (CIN) lesions, cervical cancer (CC) and genital warts (GWs). This study intended to assess the annual cost of CC, CIN and GW management in Belgium. Method: A retrospective study using a Belgian Hospital Disease Database (for yearly hospital cost of CC and GW patients) and a clinical expert survey were performed to assess the medical management of CC, CIN and GW patients. Belgian official sources were used to estimate the annual costs of management of CC, CIN and GW patients both from a healthcare payer perspectives (HCPP) and a societal perspective. Results: Based on the 667 patients diagnosed annually in Belgium with CC and an annual cost per patient of €9,716, the total annual cost of CC is €6.5 million (HCPP). The 10,495 estimated CIN 1, 2 and 3 patients led to an annual cost of €1.97 million (HCPP). The 7,989 estimated annual number of diagnosed GW patients led to an estimated annual cost of €2.53 million (HCPP). Conclusion: HPV-related diseases represent an important burden on Belgian society, especially when considering that the estimates in this study are probably underestimations, as the management costs of other HPV-related diseases (vulvar, vaginal, penile, oropharyngeal (pre-) cancers, recurrent respiratory papillomatosis etc.) are not included in this analysis.

The economic impact of using alfuzosin 10 mg once daily in the management of acute urinary retention in the UK: a 6-month analysis

To calculate the economic consequences of using alfuzosin 10 mg once daily for managing acute urinary retention (AUR) related to benign prostatic hyperplasia (BPH).

Resource use and cost of hepatitis C-related care.

Background Chronic hepatitis because of the hepatitis C virus (CHC) is a major health problem that can lead to decompensated cirrhosis, hepatocellular carcinoma, and eventually death, all of which are associated with significant healthcare costs. Aim To update the cost of care of CHC according to the different severity stages of the disease in a west European country (Belgium). Methods Medical records of 157 patients, who were referred to the medical specialist at different stages of disease, were reviewed to identify the medical costs over a follow-up period of 3 years or 2 years in the case of liver transplantation (LT). Six disease stages were defined on the basis of histology (Metavir classification) and/or clinical data. Results In comparison with mild disease, the cost increased 1.6 times in the case of decompensated cirrhosis, 1.9 times in the case of hepatocellular carcinoma, and 3.4 in the case of LT. The costs for medication, hospitalization, and ambulatory care were, respectively, on the one hand, 81, 8, and 11% for mild disease and, on the other, 18, 79, and 3% for LT. In the case of a sustained viral response, the cost of follow-up within 3 years decreased by 45% for patients with mild and moderate disease. Conclusion Antiviral treatment is the most important factor governing cost in mild and moderate disease, but once complications of CHC occur, hospitalization costs far exceed the cost of antiviral therapy. Already during the first 3 years of follow-up, sustained viral response decreased the cost significantly. Treatment of patients with CHC in an early stage has the potential to be cost-effective.

Health economic evaluation of controlled and maintained physical exercise in the prevention of cardiovascular and other prosperity diseases

Objectives Several studies and reports support the health benefits of frequent physical exercise, on the condition that this exercise is controlled and maintained. Given the scarce resources that can be spent on health and health care, the objective of this study was to evaluate the long-term health and economic outcomes of controlled and maintained physical exercise in a fitness setting. Methods A 25-year Markov model with a 12-month cycle-length and states representing diabetes, coronary heart disease, stroke, colon cancer and breast cancer was developed to predict cumulative costs and QALYs (quality adjusted life years) for three defined population cohorts, of different risk levels. Physical exercise was thereby compared with no intervention. Reduced risks associated with physical exercise, cost of diseases and loss of quality of life in case of disease were obtained from published literature. Costs were taken from a societal perspective; Belgium was selected as the setting. One way and probabilistic sensitivity analyses were carried out. Results For each of the cohorts, physical exercise is predicted to increase the QALYs and to offset a large part of the initial investment. The cost per QALY varies from €2000 to 15 000 per QALY depending on the risk levels, which is better compared with a majority of secondary preventions that are currently publicly financed. Conclusion Controlled and maintained physical exercise is projected to be cost-effective, which is likely to be explained by its simultaneous effect on several diseases and the associated weight loss, which affects quality of life positively. Eur J Cardiovasc Prev Rehabil 14: 815-824