Cost-effectiveness analysis of new generation coronary CT scanners for difficult-to-image patients.

AIMS: New generation dual-source coronary CT (NGCCT) scanners with more than 64 slices were evaluated for patients with (known) or suspected of coronary artery disease (CAD) who are difficult to image: obese, coronary calcium score > 400, arrhythmias, previous revascularization, heart rate > 65 beats per minute, and intolerance of betablocker. A cost-effectiveness analysis of NGCCT compared with invasive coronary angiography (ICA) was performed for these difficult-to-image patients for England and Wales. METHODS AND RESULTS: Five models (diagnostic decision model, four Markov models for CAD progression, stroke, radiation and general population) were integrated to estimate the cost-effectiveness of NGCCT for both suspected and known CAD populations. The lifetime costs and effects from the National Health Service perspective were estimated for three strategies: (1) patients diagnosed using ICA, (2) using NGCCT, and (3) patients diagnosed using a combination of NGCCT and, if positive, followed by ICA. In the suspected population, the strategy where patients only undergo a NGCCT is a cost-effective option at accepted cost-effectiveness thresholds. The strategy of using NGCCT in combination with ICA is the most favourable strategy for patients with known CAD. The most influential factors behind these results are the percentage of patients being misclassified (a function of both diagnostic accuracy and the prior likelihood), the complication rates of the procedures, and the cost price of a NGCCT scan. CONCLUSION: The use of NGCCT might be considered cost-effective in both populations since it is cost-saving compared to ICA and generates similar effects.

AdViSHE: A Validation-Assessment Tool of Health-Economic Models for Decision Makers and Model Users.

BACKGROUND: A trade-off exists between building confidence in health-economic (HE) decision models and the use of scarce resources. We aimed to create a practical tool providing model users with a structured view into the validation status of HE decision models, to address this trade-off. METHODS: A Delphi panel was organized, and was completed by a workshop during an international conference. The proposed tool was constructed iteratively based on comments from, and the discussion amongst, panellists. During the Delphi process, comments were solicited on the importance and feasibility of possible validation techniques for modellers, their relevance for decision makers, and the overall structure and formulation in the tool. RESULTS: The panel consisted of 47 experts in HE modelling and HE decision making from various professional and international backgrounds. In addition, 50 discussants actively engaged in the discussion at the conference workshop and returned 19 questionnaires with additional comments. The final version consists of 13 items covering all relevant aspects of HE decision models: the conceptual model, the input data, the implemented software program, and the model outcomes. CONCLUSIONS: Assessment of the Validation Status of Health-Economic decision models (AdViSHE) is a validation-assessment tool in which model developers report in a systematic way both on validation efforts performed and on their outcomes. Subsequently, model users can establish whether confidence in the model is justified or whether additional validation efforts should be undertaken. In this way, AdViSHE enhances transparency of the validation status of HE models and supports efficient model validation.

Cost-Effectiveness of Including a Nurse Specialist in the Treatment of Urinary Incontinence in Primary Care in the Netherlands.

OBJECTIVE: Incontinence is an important health problem. Effectively treating incontinence could lead to important health gains in patients and caregivers. Management of incontinence is currently suboptimal, especially in elderly patients. To optimise the provision of incontinence care a global optimum continence service specification (OCSS) was developed. The current study evaluates the costs and effects of implementing this OCSS for community-dwelling patients older than 65 years with four or more chronic diseases in the Netherlands. METHOD: A decision analytic model was developed comparing the current care pathway for urinary incontinence in the Netherlands with the pathway as described in the OCSS. The new care strategy was operationalised as the appointment of a continence nurse specialist (NS) located with the general practitioner (GP). This was assumed to increase case detection and to include initial assessment and treatment by the NS. The analysis used a societal perspective, including medical costs, containment products (out-of-pocket and paid by insurer), home care, informal care, and implementation costs. RESULTS: With the new care strategy a QALY gain of 0.005 per patient is achieved while saving €402 per patient over a 3 year period from a societal perspective. In interpreting these findings it is important to realise that many patients are undetected, even in the new care situation (36%), or receive care for containment only. In both of these groups no health gains were achieved. CONCLUSION: Implementing the OCSS in the Netherlands by locating a NS in the GP practice is likely to reduce incontinence, improve quality of life, and reduce costs. Furthermore, the study also highlighted that various areas of the continence care process lack data, which would be valuable to collect through the introduction of the NS in a study setting.

[Guideline 'NSAID use and the prevention of gastric damage']. / Richtlijn 'NSAID-gebruik en preventie van maagschade'.

Supported by the Dutch Institute for Health Care Improvement (CBO), a committee consisting of rheumatologists, general practitioners, gastroenterohepatologists, hospital pharmacists and a health-economist have developed a national evidence-based guideline for the prevention of gastric damage by non-steroidal anti-inflammatory drugs (NSAIDs). The goal of the guideline is to reduce the number of gastric ulcers with perforation or bleeding as a consequence of NSAID use. It is estimated that 165 patients died as a result of these complications in the year 2000. The guideline comprises chapters on the risk factors for ulceration during NSAID use, the effectiveness and relative toxicity of different NSAIDs for the stomach, the effectiveness of various treatments meant to reduce the risk of gastro-duodenal damage, and the management of dyspeptic symptoms during NSAID use. A strategy is recommended in which prescription of NSAIDs is always preceded by an assessment of the degree to which the risk of gastric damage is increased: the most important risk factors that need to be identified are previous peptic ulcer disease, age over 70 years, and an untreated Helicobacter pylori infection associated with peptic ulcer disease. Whenever an increased risk of gastro-duodenal damage is present, the prescribing physician can choose one of three preventive strategies: addition of misoprostol, addition of a proton-pump inhibitor, or the prescription of a COX-2-selective NSAID. Provided that adequate risk assessment has been carried out, the guideline leaves it to the patient and physician to choose which of these preventive measures, all of which result in roughly equal risk reduction and costs, is the most suitable for individual situations. The use of aspirin or a coumarin derivative increases the risk; several preventive strategies are possible; the guideline discusses the situation that arises when NSAIDs are added to the treatment.

One-year cost-effectiveness of tiotropium versus ipratropium to treat chronic obstructive pulmonary disease.

The aim of this paper is to assess the health economic consequences of substituting ipratropium with the new, once-daily bronchodilator tiotropium in patients with a diagnosis of chronic obstructive pulmonary disease (COPD). This prospective cost-effectiveness analysis was performed alongside two 1-yr randomised, double-blind clinical trials in the Netherlands and Belgium. Patients had a diagnosis of COPD and a forced expiratory volume in one second (FEV1) < or = 65% predicted normal. Patients were randomised to tiotropium (18 microg once daily) or ipratropium (2 puffs of 20 microg administered four times daily) in a ratio of 2:1. The mean number of exacerbations was reduced from 1.01 in the ipratropium group (n = 175) to 0.74 in the tiotropium group (n = 344). The percentages of patients with a relevant improvement on the St. George's Respiratory Questionnaire (SGRQ) were 34.6% and 51.2%, respectively. Compared to ipratropium, the number of hospital admissions, hospital days and unscheduled visits to healthcare providers was reduced by 46%, 42% and 36% respectively. Mean annual healthcare costs including the acquisition cost of the study drugs were 1721 Euro (SEM 160) in the tiotropium group and 1,541 Euro (SEM 163) in the ipratropium group (difference 180 Euro). Incremental cost-effectiveness ratios were 667 Euro per exacerbation avoided and 1084 Euro per patient with a relevant improvement on the SGRQ. Substituting tiotropium for ipratropium in chronic obstructive pulmonary disease patients offers improved health outcomes and is associated with increased costs of 180 Euro per patient per year.

Long term outcome and cost-effectiveness of stenting versus balloon angioplasty for acute myocardial infarction.

OBJECTIVE: To investigate the long term clinical outcome and cost-effectiveness of stenting compared with balloon angioplasty in patients with acute myocardial infarction. METHODS: Patients with acute myocardial infarction were randomly allocated to primary stenting (112) or balloon angioplasty (115). The primary end point was the cumulative first event rate of death, non-fatal reinfarction, or target vessel revascularisation. Secondary end points were restenosis at six months and the cost-effectiveness at follow up. RESULTS: After 24 months, the combined clinical end point of death/reinfarction was 4% after stenting and 11% after balloon angioplasty (p = 0.04). Subsequent target vessel revascularisation was necessary in 15 patients (13%) after stenting and in 39 (34%) after balloon angioplasty (p < 0.001). The cumulative cardiac event-free survival rate was also higher after stenting (84% v 62%, p < 0.001). The angiographic restenosis rate after stenting was less than after balloon angioplasty (12% v 34%, p < 0.001). Despite the higher initial costs of stenting (Dfl 21 484 v Dfl 18 625, p < 0.001), the cumulative costs at 24 months were comparable with those of balloon angioplasty (Dfl 31 423 v Dfl 32 933, p = 0.83). CONCLUSIONS: Compared with balloon angioplasty, primary stenting for acute myocardial infarction results in a better long term clinical outcome without increased cost.

Healthcare resource utilisation and costs of treating NSAID-associated gastrointestinal toxicity. A multinational perspective.

OBJECTIVE: The aim of the study was to perform an economic analysis of a new therapy in 11 countries (Australia, Belgium, Finland, France, Germany, Italy, The Netherlands, Spain, Sweden, Switzerland and the UK) to assess the cost of treating the gastrointestinal (GI) events associated with the use of nonsteroidal anti-inflammatory drugs in patients with osteoarthritis and rheumatoid arthritis. METHODS: Estimates of GI event-related costs were based on the results of resource utilisation questionnaires. Resources required for the treatment and follow-up of GI events were identified and converted into costs from society and payer perspectives. RESULTS: From the perspective of society, the total per-event cost of managing GI-related events varies from $US51 to $US772 for GI discomfort, from $US108 to $US1100 for anaemia, from $US145 to $US1200 for ulcer and from $US1923 to $US5473 for serious GI events requiring hospitalisation. From the payer perspective, the total per-event cost varies from $US47 to $US680 for GI discomfort, from $US144 to $US762 for anaemia, from $US229 to $US795 for ulcer and from $US1787 to $US6729 for serious GI events requiring hospitalisation. The total cost is driven by hospital expenses for those events requiring hospital admission. For GI discomfort, physician consultations are generally the cost driver, whereas for ulcer and anaemia, cost is primarily driven by the rate of endoscopy. CONCLUSIONS: Costs associated with nonsteroidal anti-inflammatory drug-related GI events differ significantly across countries as a result of variations in resources consumed and price/tariff policies.

A Bayesian approach to economic analyses of clinical trials: the case of stenting versus balloon angioplasty.

New results about the costs and effects of a new therapy may be weighted with prior information. As such, classical confidence intervals surrounding the costs and effects of a therapy may not reflect the real uncertainties. Bayesian techniques may improve this by formalizing the way that prior information is taken into account in assessing the new evidence. Costs and effects can be analysed separately, but also, when considering the balance between costs and effects, they can be analysed simultaneously. Here, an example is given using data from two trials that compared costs and effectiveness of stent implantation with balloon angioplasty. The Bayesian results make it clear that different prior distributions may lead to different decisions, and it is concluded that even Bayesian analysis may not always reflect the process of capturing the remaining uncertainties.

The relation between TISS and real paediatric ICU costs: a case study with generalizable methodology.

OBJECTIVE: To determine the quantitative relation between the Therapeutic Intervention Scoring System (TISS) in combination with other relevant clinical variables and the real costs of (paediatric) intensive care. DESIGN: A prospective, observational study. SETTING: A Ten-bed paediatric intensive care unit in a university children's hospital. PATIENTS AND PARTICIPANTS: In a 17-months registration period we collected patient- and treatment-related data for all 611 consecutive admissions. A 21-day calibration period was used to collect detailed data to calculate the real costs of 33 consecutive admissions, in addition to the same data as in the registration period. MEASUREMENTS AND RESULTS: We used the Multi Moment Measurement method to measure time spent by nurses and physicians and medication used in the 21-day calibration period. The calibration period data set with explanatory variables including TISS was used to build a regression model to estimate nurse and physician time, which were converted to personnel costs, and to estimate medication costs. The regression models built from the calibration period were subsequently used to estimate the total costs per day and per admission in different patient groups in the registration period. CONCLUSION: It was feasible to calculate total direct medical costs based on a limited number of readily available clinical variables related to patient characteristics and treatment, of which TISS was the most important determinant. The proposed methods provide further tools for assessment of (paediatric) intensive care unit performance.

Sample size calculation in economic evaluations.

A simulation method is presented for sample size calculation in economic evaluations. As input the method requires: the expected difference and variance of costs and effects, their correlation, the significance level (alpha) and the power of the testing method and the maximum acceptable ratio of incremental effectiveness to incremental costs. The method is illustrated with data from two trials. The first compares primary coronary angioplasty with streptokinase in the treatment of acute myocardial infarction, in the second trial, lansoprazole is compared with omeprazole in the treatment of reflux oesophagitis. These case studies show how the various parameters influence the sample size. Given the large number of parameters that have to be specified in advance, the lack of knowledge about costs and their standard deviation, and the difficulty of specifying the maximum acceptable ratio of incremental effectiveness to incremental costs, the conclusion of the study is that from a technical point of view it is possible to perform a sample size calculation for an economic evaluation, but one should wonder how useful it is.

Technology assessment of the Dutch Lung Transplantation Program.

The costs, effects, and cost-effectiveness of the Dutch Lung Transplantation program were assessed. The results show that lung transplantation is a very costly intervention that improves survival and quality of life. Costs per life-year and per QALY gained were, respectively, US $90,000 and US $71,000.

Cost-effectiveness of lung transplantation in The Netherlands: a scenario analysis.

STUDY OBJECTIVES: To calculate cost-effectiveness of scenarios concerning lung transplantation in The Netherlands. DESIGN: Microsimulation model predicting survival, quality of life, and costs with and without transplantation program, based on data of the Dutch lung transplantation program of 1990 to 1995. SETTING: Netherlands, University Hospital Groningen. PATIENTS: Included were 425 patients referred for lung transplantation, of whom 57 underwent transplantation. INTERVENTION: Lung transplantation. RESULTS: For the baseline scenario, the costs per life-year gained are G 194,000 (G=Netherlands guilders) and the costs per quality-adjusted life-year (QALY) gained are G 167,000. Restricting patient inflow ("policy scenario") lowers the costs per life-year gained: G 172,000 (costs per QALY gained: G 144,000). The supply of more donor lungs could reduce the costs per life-year gained to G 159,000 (G 135,000 per QALY gained; G1 =US $0.6, based on exchange rate at the time of the study). CONCLUSIONS: Lung transplantation is an expensive but effective intervention: survival and quality of life improve substantially after transplantation. The costs per life-year gained are relatively high, compared with other interventions and other types of transplantation. Restricting the patient inflow and/or raising donor supply improves cost-effectiveness to some degree. Limiting the extent of inpatient screening or lower future costs of immunosuppressives may slightly improve the cost-effectiveness of the program.

The cost effectiveness of diclofenac plus misoprostol compared with diclofenac monotherapy in patients with rheumatoid arthritis.

The objective of our study was to estimate the cost effectiveness of treatment with a fixed-dose combination of diclofenac and misoprostol compared with diclofenac monotherapy in the prevention of nonsteroidal anti-inflammatory drug (NSAID)-induced ulcers in rheumatoid arthritis (RA) patients. A model was used to incorporate estimates of costs, incidence of ulcers and their complications, death rates and the efficacy of misoprostol. The costs per ulcer-free period gained and costs per additional survivor were calculated. Cost effectiveness was calculated for the treatment of all RA patients, and of risk groups only. All costs were measured in 1995 Netherlands guilders (NLG; exchange rate at the time of the study: NLG1 = $US0.60). The analysis showed that if 100 RA patients receive 3 months of treatment with diclofenac plus misoprostol, instead of diclofenac alone, this will lead to overall additional costs of NLG773, while 0.82 symptomatic ulcers and 0.019 deaths will be prevented. If misoprostol is given only to patients at high risk for NSAID-induced ulcer, cost savings will occur instead of additional costs. Univariate sensitivity analysis showed that the outcomes are sensitive to changes in: (i) the percentage of ulcers treated in the ambulatory setting; (ii) the price difference between diclofenac and the fixed-dose diclofenac-misoprostol combination; (iii) the percentage of ulcers with complications; and (iv) the efficacy of misoprostol. In conclusion, it can be stated that treatment with diclofenac-misoprostol is cost saving in RA patients at high risk for NSAID-induced ulcers. For RA patients in general, the cost-effectiveness of this intervention compares favourably with that of other prophylactic treatments.

Economic aspects of treatment with captopril for patients with asymptomatic left ventricular dysfunction in The Netherlands.

OBJECTIVE: To estimate the costs and effects of preventive treatment with captopril compared with the current treatment policy in patients with asymptomatic left ventricular dysfunction after a myocardial infarction. METHODS: Estimates of effects are based on the results of the SAVE trial. Costs are estimated on the basis of current treatment patterns in four Dutch hospitals. All knowledge is incorporated in a mathematical model extrapolating the SAVE results to 20 years. RESULTS AND CONCLUSIONS: Captopril treatment is expected to increase survival at certain costs. The average additional costs per patient are estimated at DF1 2,491 in 4 years and at DF1 8,723 in 20 years of treatment. Costs per additional survivor after 4 years are estimated at DF1 69,126. After extrapolation of the results of the SAVE trial to 20 years, costs per life-year gained can be estimated at DF1 15,799. From univariate sensitivity analysis it appears that the results are highly sensitive for the costs of treatment with captopril and the occurrence and prevention of clinical heart failure. Varying all estimates randomly between upper and lower limits-in 5,000 simulations-an estimate of costs per life-year gained of DF1 15,729 is made for 20 years of treatment, with 95% of all estimates between DF10 and DF1 50, 000. On a national level, undiscounted costs are expected to increase up to approximately DF1 42 million annually during the first 40 years after introduction of the preventative strategy.

Costs, effects and C/E-ratios alongside a clinical trial.

A general approach is discussed to assess the uncertainty surrounding the cost effectiveness ratio (C/E-ratio) estimated on the basis of data from a randomised clinical trial. The approach includes the calculation of a 95% probability ellipse and introduces the concept of a so called C/E-acceptability curve. This last curve defines for each predefined C/E-ratio the probability that the C/E-ratio found in the study is acceptable. The approach is illustrated by estimates of costs per life saved and costs per patient discharged alive on the basis of data from a phase II trial addressing the value of anakinra in treating sepsis syndrome.