Bowine C. Michel

Societal Perspective on the Burden of Migraine in The Netherlands

SummaryThis study presents a comprehensive overview of the societal burden of migraine in The Netherlands. We assessed the direct and indirect costs of this disease, and the health status of patients with migraine. We developed the ‘illness and labour’ (I&) questionnaire to collect data on the effect of illness on labour performance 846 migraine patients and 834 controls were selected from the general population. Participants completed an I&L questionnaire as wel l as generic health status questionnaires.The direct costs of migraine amounted to 134 million Netherlands guilders (NLG) [

Redundancy of single diagnostic test evaluation

US1=NLG1.68, October 1994]. Conservative calculations of the costs of absence from work and reduced productivity at work were NLG264 and NLG277 million per year respectively. Our study did not indicate that migraine caused household productivity losses. The baseline estimate of the total societal costs of migraine in The Netherlands was NLG675 million per year. The assessment of health status showed considerable impairment of psychological and social functioning in migraine patients.

The role of plasma D-dimer concentration in the exclusion of pulmonary embolism

Diagnostic research and diagnostic practice frequently do not cohere. Studies commonly evaluate whether a single test discriminates between disease presence and absence, whereas in practice a test is always judged in the context of other information. This study illustrates drawbacks of single-test evaluation and discusses principles of diagnostic research. We used data on 140 patients suspected of pulmonary embolism who had an inconclusive ventilation-perfusion lung scan. We evaluated three tests: partial pressure of oxygen in arterial blood (PaO2), x-ray film of the thorax, and leg ultrasound. On the basis of single-test evaluations, ultrasound was most informative. Given a prior probability of 0.27, it had a much better combination of positive and negative predictive value (0.71 and 0.21, respectively) relative to thorax x-ray (0.33 and 0.11) and PaO2 (0.35 and 0.27). The combination of positive and negative likelihood ratio was also more promising for ultrasound (7.3 and 0.7) than for thorax x-ray (1.3 and 0.3) and PaO2 (1.3 and 0.9). As the tests are always performed after the history and physical, we judged their added value using multivariable logistic modeling with receiver operating characteristic (ROC) analyses. The ROC areas of the model, including history and physical, with additional PaO2, thorax x-ray, or ultrasound, were 0.75, 0.77, 0.81, and 0.81, respectively, which indicated similar added value of thorax x-ray and ultrasound. Application of the models to patient subgroups also yielded added predictive value for thorax x-ray film. Thus, the results of single-test evaluations may be very misleading. As no diagnosis is based on one test, single-test evaluations have limited value in diagnostic research and only have relevance in the context of screening and the initial phase of test development. Diagnostic research should always apply an approach of constructing, extending, and validating diagnostic models in agreement with routine clinical work-up using logistic regression analyses.

Application of Treatment Thresholds to Diagnostic-test Evaluation An Alternative to the Comparison of Areas under Receiver Operating Characteristic Curves

Objective. To determine the role of four ELISA D‐dimer assays in the exclusion of pulmonary embolism.

Sample size calculation in economic evaluations

Diagnostic tests are often evaluated by comparison of the areas under receiver op erating charactenstic (ROC) curves. In this study the authors compared this approach with a more direct method that takes into account consequences of a diagnosis. Data from a prospective study of diagnosis of pulmonary embolism were used for a moti vating example. Using multivariable logistic regression analysis, three diagnostic mod els were built and compared based on their ROC curves. Although model 1 (0.706) and model 2 (0.702) had the same ROC-curve area, they performed differently when risks and benefits of subsequent decisions were considered by applying the treatment probability threshold. Models 1 and 3 (0.611) had substantially different ROC-curve areas but performed similarly taking into account the therapeutic consequences. This demonstrates that comparison of diagnostic tests using the areas under the ROC curves may lead to erroneous conclusions about therapeutic usefulness. To corre spond to daily practice, it would be more appropriate to also consider the clinical im plications in evaluating diagnostic tests. This is made feasible by explicit definition and application of a treatment threshold. Key words: benefits and risks; clinical relevance; diagnosis; diagnostic test evaluation; ROC curve; treatment threshold. (Med Decis Making 1997;17:447-454)

3 Assessing the benefits of transplant services

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.

The cost-effectiveness of diagnostic strategies in patients with suspected pulmonary embolism

This chapter presents some methods for the assessment of transplant benefits, using the example of liver transplantation. An independent assessment of the benefits of medical technology is especially important for evaluation of the balance between the costs and benefits involved. To enable comparison with other health-care facilities, benefits are defined in terms of a combination of life-years gained and quality of life. The number of life-years gained can be calculated by comparing the survival expected with and without transplantation. Survival with transplantation is estimated on the basis of observed survival, acknowledging that the probability of survival may have changed over time, owing to changes in therapy and selection criteria. To estimate survival without transplantation, several techniques are available. Prognostic models, correcting for stage of disease, are often used. Pitfalls in the use of these models are discussed. The number of life-years gained can be corrected for quality of life by weighing survival with and without transplantation with an index representing quality of life. A method for the calculation of such an index is given. Finally, some cost estimates are presented and the results are discussed.

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

The cost-effectiveness of various diagnostic strategies in patients with clinically suspected pulmonary embolism (PE) was analysed using a modelling approach. In 451 consecutive patients with clinically suspected PE data on the performance of diagnostic tests were collected prospectively in two large teaching hospitals in Amsterdam, The Netherlands. The ventilation-perfusion lung scan was used as the primary diagnostic test in all patients. In patients with a non-diagnostic lung scan result the performance of a clinical decision rule, a D-dimer test, and ultrasonography of the leg veins was evaluated with pulmonary angiography as the gold standard. It was estimated that the strategy recommended by a 1992 Dutch consensus meeting costs about Dfl 4400 per patient and that 97.02% of the patients can be expected to survive the first 6 months after the primary PE. The nation-wide annual costs for the diagnosis and treatment of patients by this strategy were estimated at 163 million Dutch Guilders. Subsequently, the costs and effects of alternative strategies were evaluated in a modelling approach, and compared with those of the consensus strategy. One strategy was selected that produces the best results in terms of survival and leads to considerable savings as compared with the consensus strategy. In this strategy subsequently a ventilation-perfusion scan, a clinical decision rule, a D-dimer test, a pulmonary angiography and leg ultrasonography are performed. Patients with a high probability ventilation-perfusion scan, an abnormal angiography or leg ultrasound test are treated, whereas treatment is withheld in patients with a normal ventilation-perfusion scan, a normal clinical decision rule, a negative D-dimer test, a normal angiography, or a normal leg ultrasound test. This strategy will have to prove its value and usefulness in clinical practice in a subsequent prospective validation phase.

Simulation models in the planning of health care facilities: an application in the case of neonatal extracorporeal membrane oxygenation.

SummaryThe 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 =

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

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.