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de Graaf R, ten Have M, Beekman A. Economic costs of minor depression: a population-based study.Objective: Although the clinical relevance of minor depression has been demonstrated in many studies, the economic costs are not well explored. In this study, we examine the economic costs of minor depression. Method: In a large-scale, population-based study in the Netherlands (n ¼ 5504) the costs of minor depression were compared with the costs of major depression and dysthymia. Excess costs, i.e. the costs of a disorder over and above the costs attributable to other illnesses, were estimated with help of regression analysis. The direct medical costs, the direct non-medical costs and the indirect non-medical costs were calculated. The year 2003 was used as the reference year. Results: The annual per capita excess costs of minor depression were US$ 2141 (95% CI ¼ 753-3529) higher than the base rate costs of US$ 1023, while the costs of major depression were US$ 3313 (95% CI ¼ 1234-5390) higher than the base rate. The costs of minor depression per 1 million inhabitants were 160 million dollars per year, which is somewhat less than the costs of major depression (192 million dollars per year). Conclusion:The economic costs associated with minor depression are considerable and approach those of major depression. Significant outcomes • The annual excess per capita costs of minor depression are about two-thirds of the per capita costs of major depression.• Per million inhabitants the excess costs of minor depression (US$ 160 million) approach those of major depression (US$ 192 million).• Virtually all excess costs of minor depression are indirect non-medical costs (costs for treatment are not significantly higher than the base rate). Limitations• The definition of minor depression was not exactly the same as the DSM-IV definition.• Although the number of subjects was large, it is relatively small for economic studies.• Data from the second measurement point of the study were used, at which point some attrition had already taken place.

This probabilistic model-based economic evaluation demonstrates how clinical trial data can be combined and integrated with country-specific information about resource utilization and unit cost to assess the cost-effectiveness of bronchodilators in COPD patients. Quality-adjusted life months did not substantially differ between treatment groups. In terms of exacerbations, tiotropium was associated with maximum expected net benefit for plausible values of the ceiling ratio. In sensitivity analyses, this outcome was most sensitive to changes in exacerbation rates.

The lack of a uniform costing methodology is often considered a weakness of economic evaluations that hinders the interpretation and comparison of studies. Standardisation is therefore an important topic within the methodology of economic evaluations and in national guidelines that formulate the formal requirements for studies to be considered when deciding on the reimbursement of new medical therapies. Recently, the Dutch Manual for Costing: Methods and Standard Costs for Economic Evaluations in Health Care (further referred to as "the manual") has been published, in addition to the Dutch guidelines for pharmacoeconomic research. The objectives of this article are to describe the main content of the manual and to discuss some key issues of the manual in relation to the standardisation of costs. The manual introduces a six-step procedure for costing. These steps concern: the scope of the study;the choice of cost categories;the identification of units;the measurement of resource use;the monetary valuation of units; andthe calculation of unit costs. Each step consists of a number of choices and these together define the approach taken. In addition to a description of the costing process, five key issues regarding the standardisation of costs are distinguished. These are the use of basic principles, methods for measurement and valuation, standard costs (average prices of healthcare services), standard values (values that can be used within unit cost calculations), and the reporting of outcomes. The use of the basic principles, standard values and minimal requirements for reporting outcomes, as defined in the manual, are obligatory in studies that support submissions to acquire reimbursement for new pharmaceuticals. Whether to use standard costs, and the choice of a particular method to measure or value costs, is left mainly to the investigator, depending on the specific study setting. In conclusion, several instruments are available to increase standardisation in costing methodology among studies. These instruments have to be used in such a way that a balance is found between standardisation and the specific setting in which a study is performed. The way in which the Dutch manual tries to reach this balance can serve as an illustration for other countries.

Our objective was to assess the 5-year cost effectiveness of bronchodilator therapy with tiotropium, salmeterol or ipratropium for chronic obstructive pulmonary disease (COPD) from the perspective of the Spanish National Health System (NHS). A probabilistic Markov model was designed wherein patients moved between moderate, severe or very severe COPD and had the risk of exacerbation and death. Probabilities were derived from clinical trials. Spanish healthcare utilisation, costs and utilities were estimated for each COPD and exacerbation state. Outcomes were exacerbations, exacerbation-free months, qualityadjusted life years (QALYs), and cost(-effectiveness). The mean (SE) 5-year number of exacerbations was 3.50 (0.14) for tiotropium, 4.16 (0.40) for salmeterol and 4.71 (0.54) for ipratropium. The mean (SE) number of QALYs was 3.15 (0.08), 3.02 (0.15) and 3.00 (0.20), respectively. Mean (SE) 5-year costs were e6,424 (e305) for tiotropium, e5,869 (e505) for salmeterol, and e5,181 (e682) for ipratropium (2005 values). Ipratropium and tiotropium formed the costeffectiveness frontier, with tiotropium being preferred when willingness to pay (WTP) exceeded e639 per exacerbation-free month and e8,157 per QALY. In Spain, tiotropium demonstrated the highest expected net benefit for ratios of the willingness to pay per QALY, well within accepted limits.Keywords Chronic obstructive pulmonary disease (COPD) Á Bronchodilators Á Model Á Cost effectiveness Á Quality-adjusted life year (QALY) Á Spain

One-year cost-effectiveness of tiotropium versus ipratropium to treat chronic obstructive pulomonary disease. J.B. Oostenbrink, M.P.M.H. Rutten-van Mölken, M.J. Al, J.A. Van Noord, W. Vincken. #ERS Journals Ltd 2004. ABSTRACT: 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) f65% predicted normal. Patients were randomised to tiotropium (18 mg once daily) or ipratropium (2 puffs of 20 mg 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. George9s 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 J1721 (SEM 160) in the tiotropium group and J1,541 (SEM 163) in the ipratropium group (difference J180). Incremental costeffectiveness ratios were J667 per exacerbation avoided and J1084 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 J180 per patient per year.

Incomplete data due to premature withdrawal (dropout) constitute a serious problem in prospective economic evaluations that has received only little attention to date. The aim of this simulation study was to investigate how standard methods for dealing with incomplete data perform when applied to cost data with various distributions and various types of dropout. Selected methods included the product-limit estimator of Lin et al. the expectation maximisation (EM-) algorithm, several types of multiple imputation (MI) and various simple methods like complete case analysis and mean imputation. Almost all methods were unbiased in the case of dropout completely at random (DCAR), but only the product-limit estimator, the EM-algorithm and the MI approaches provided adequate estimates of the standard error (SE). The best estimates of the mean and SE for dropout at random (DAR) were provided by the bootstrap EM-algorithm, MI regression and MI Monte Carlo Markov chain. These methods were able to deal with skewed cost data in combination with DAR and only became biased when costs also included the costs of expensive events. None of the methods were able to deal adequately with informative dropout. In conclusion, the EM-algorithm with bootstrap, MI regression and MI MCMC are robust to the multivariate normal assumption and are the preferred methods for the analysis of incomplete cost data when the assumption of DCAR is not justified.

Patients hospitalised for exacerbations contribute significantly to the total chronic obstructive pulmonary disease (COPD)-related healthcare costs. This study aimed to determine the resource use and costs of exacerbations by exacerbation-severity and to identify risk factors for hospitalisation. Exacerbations and the details of all associated healthcare utilisation were recorded as part of a prospective cost-effectiveness analysis linked to two randomised controlled trials comparing tiotropium with ipratropium in 519 patients with stable COPD at study entry in the Netherlands and Belgium. Exacerbation-severity was rated by the physician. A Cox proportional hazards analysis was performed to identify independent risk factors of hospitalisation. Covariates that entered this analysis were smoking status, pack-years, body mass index, number of concomitant diseases, number of concomitant medications, use of inhaled steroids, physician visits prior to trial, FEV1% predicted, quality of life, baseline dyspnea index (BDI) and treatment arm. The mean number of exacerbations per patient was 0.70 (95%-CI:0.60, 0.81). About 10% of the exacerbations was severe, 47% moderate and 43% was mild. The mean costs of these exacerbations were Euro 4007 (95%-CI:2004, 6011), Euro 579 (390, 768) and Euro 86 (49, 124), respectively. In addition to treatment arm, a body mass index below 18.5 (RR:3.62), each additional concomitant diagnosis (RR:1.40) and a decrease of 1 point in the baseline dyspnea index (RR:1.18) were significant risk factors of hospitalisation. Exacerbations that were associated with a hospitalisation accounted for 90% of the total costs of exacerbations. Underweight, history of concomitant diseases and increased dyspnea (BDI score) are factors that are likely to identify patients who are at increased risk for generating high costs due to hospitalisation.