THE ECONOMIC BURDEN OF OCCUPATIONAL ASTHMA IN EUROPE

Huo Jinhai

2010

Supervisor: Senior Lecturer: Håkan Brodin Swedish National Institute of Public Health

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“Safe work is not only sound economic policy; it is a basic human right…” (Kofi Annan, former secretary-general of the United Nations)

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ABSTRACT

Aim: The aim of the present study was to perform cost estimation of total costs of occupational asthma in Europe from the perspective of society based on published epidemiologic and economic evidence. Methods: A model simulated the cost of occupational asthma by combining epidemiological and economic data on occupational asthma in thirty-two European countries. The data collected from extensive literature reviews of epidemiology and economic burden of occupational asthma and general asthma were analyzed. Individual case costs were estimated and calculated as annual cost and epidemiological data was reported as 12-month incidence estimates. Results: The total annual cost of occupational asthma in Europe was estimated at €1.2 billion in 2008. Direct cost alone totaled €335 million. Indirect cost is comprised of individual (€409 million), employee (€68 million) and society (€385 million). Conclusion: In conclusion, the cost of occupational asthma poses a significant economic burden to the European Union. These costs maybe reduced with enhancing occupational health surveillance systems in Europe, and the burden of long-term illness and public health costs would be reduced. Keywords: Occupational asthma, Incidence rate, Geographical variance, Cost of illness; Cost, Cost analysis

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TABLE OF CONTENTS

ABSTRACT........................................................................................................................................................... 3

TABLE OF CONTENTS...................................................................................................................................... 4

LIST OF TABLES................................................................................................................................................. 5

LIST OF FIGURES .............................................................................................................................................. 6

LIST OF ABBREVIATIONS............................................................................................................................... 7

1. BACKGROUND ............................................................................................................................................... 8

OCCUPATIONAL ASTHMA...................................................................................................................................... 8 Definition........................................................................................................................................................ 8 Diagnosis ........................................................................................................................................................ 8 Pathology........................................................................................................................................................ 9 Treatments for occupational asthma............................................................................................................. 10 Surveillance System ...................................................................................................................................... 10

ECONOMICS EVALUATION IN HEALTH CARE.........................................................................................................11 The different types of economics evaluation ..................................................................................................11 Cost................................................................................................................................................................11 Costing.......................................................................................................................................................... 12 Cost of illness................................................................................................................................................ 13

2. JUSTIFICATION............................................................................................................................................ 14

3. AIMS ................................................................................................................................................................ 14

4. MATERIALS AND METHODS.................................................................................................................... 15

DATA MATERIALS ............................................................................................................................................... 15 INCIDENCE......................................................................................................................................................... 15 DIRECT COSTS.................................................................................................................................................... 15 INDIRECT COSTS................................................................................................................................................. 16 COSTING MODEL................................................................................................................................................ 17 TIME FRAME ...................................................................................................................................................... 19 RATES ................................................................................................................................................................ 19 DISCOUNTING .................................................................................................................................................... 20 ANALYSIS TOOLS ............................................................................................................................................... 20 SENSITIVITY ANALYSIS ...................................................................................................................................... 20

5. RESULTS......................................................................................................................................................... 21

INCIDENCE OF THE OCCUPATIONAL ASTHMA ...................................................................................................... 21 COST PER CASE BY COUNTRY ............................................................................................................................. 22 COST FOR OCCUPATIONAL ASTHMA.................................................................................................................... 24 COST OF OCCUPATIONAL ASTHMA DISTRIBUTED BY RESOURCE CATEGORY......................................................... 24 SENSITIVITY ANALYSIS ...................................................................................................................................... 26

6. DISCUSSION .................................................................................................................................................. 27

7. LIMITATIONS................................................................................................................................................ 29

8. CONCLUSION ............................................................................................................................................... 30

9. REFERENCES................................................................................................................................................ 32

10. APPENDIXES ............................................................................................................................................... 36

APPENDIX I. CURRENCY RATE IN THIS ARTICLE.............................................................................................. 37 APPENDIX II. HARMONIZED INDICES OF CONSUMER PRICES ........................................................................... 37 APPENDIX VIII. STATISTICS DATA IN EUROPE USED IN THIS THESIS................................................................. 38

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LIST OF TABLES

TABLE 1 INCIDENCE INPUT DATA IN OCCUPATIONAL ASTHMA (12-MONTH, CASES PER MILLION WORKERS)............................................................................................................................. 16

TABLE 2 COST INPUT DATA IN OCCUPATIONAL ASTHMA..............................................................18 TABLE 3 COST OF OCCUPATIONAL ASTHMA BY COUNTRY (€PPP MILLION, 2008) ...................25

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LIST OF FIGURES

FIGURE 1 PATHOLOGY OF OCCUPATIONAL AGENTS .......................................................................9 FIGURE 2 INCIDENCE RATES OF OCCUPATIONAL ASTHMA IN EUROPEAN COUNTRIES ............... 21 FIGURE 3 DISTRIBUTION OF INCIDENCE RATE OF OCCUPATIONAL ASTHMA IN EUROPE ...........22 FIGURE 4 COST PER CASE WITH OCCUPATIONAL ASTHMA IN EUROPE IN 2008........................23 FIGURE 5 DISTRIBUTION OF COST OF OCCUPATIONAL ASTHMA IN EUROPE BY RESOURCE

CATEGORY .............................................................................................................................24

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LIST OF ABBREVIATIONS

APCs Anti-presenting cells CHF Swiss Franc COI Cost of illness DKK Danish Kroner EBSCO Elton B. Stephens. Company EU European Union EUR Euro FEV1 Forced Expiratory Volume GBP Great Britain Pound GDP Gross Domestic Product HICP Harmonized indices of consumer prices HMW High-Molecular-Weight IL Interleukin ILO International Labor Office ISI Institute for Scientific Information LABA Long Acting Beta-Agonists LKTRA Leukotriene Receptor Antagonists LMW How-Molecular-Weight LWW Lippincott Williams & Wilkins N Number N/A Not Available NICE National Institute of Health and Clinical Excellence NOK Norwegian Kroner NSBP Non-Specific Bronchial Provocation OA Occupational asthma PAR Proportional Attributable Risk PEF Peak Expiratory Flow PPP Purchasing Power Parity QoL Quality of Life SEK Swedish Kroner SIC Specific Inhalation Challenge SG Standard Gamble TTO Time Trade Off UK United Kingdom US United States USD United States Dollars VIF Variance Inflation Factor WTP Willingness to Pay

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1. BACKGROUND

Occupational asthma

Definition

Occupational asthma is a lung disease characterized by variable air flow limitation and/or airway hyper-responsiveness as a result of exposure to irritants which are attributable to a particular occupational environment in the workplace[1] Occupational asthma is included in the work-related asthma, which has a broader boundary. It is defined as the asthma where substances from workplace irritate the airways of patients who may or may not have had asthma before. Occupational asthma can be subdivided into two types: Aggravation of preexisting asthma: this kind of asthma has a latency period from first time exposed to asthmagens to development of a hypersensitivity symptom. Irritant asthma: has a very short latency period typically only a few hours after expose to the high concentrated respiratory sensitizers, such as irritate gas, fume, vapor and powder.[2]

Diagnosis

The most common symptoms of occupational asthma are similar as normal asthma, such as coughing, wheezing, shortness of breath, chest pain, chest tightness, extreme tiredness. The symptoms from the other parts of the body than the respiratory system could occur, for instance, itchy eyes, red or irritated skin. For some people, the symptoms appear after work or even in the weekend, while others have strong symptoms immediately when they enter the workshop. The symptoms could start in a milder way, and then gradually aggravate in the next days or weeks. These characteristics of occupational asthma make it complicated diagnose to make a diagnosis. Confirming that people have asthma is the first step to make a diagnosis of occupational asthma. Today, it is not very hard to test the existence of asthma. For example, the following tools could be used in examination. Spirometry, which is a test that measures how much air a person exhale and how powerfully a person can breathe out, with the medical staff. The criteria for the diagnosis of asthma with spirometry are: a 12-15 % of more significant improvement of forced expiratory volume (FEV1) from the baseline 15 minutes when an inhaled short acting beta 2 agonist is used; or 20% or greater "spontaneous variability" in spirometry values. Peak flow meter, which is another way of assessing how powerful a person can breathe out during an asthma attack, is handy device and can be used at the workplace. The criteria for a person to be diagnosed with asthma with Serial measures of peak expiratory flow (PEF) are: A >20% change after administration of a bronchodilator; a 20% change in values over time[3].

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The second step is to identify the potential sensitizer to which the person has been exposed in the history. It is not easy to discover these sensitizers. According to the current research, the list of these sensitizers is very long (See Appendix 7.8). However the possibility to find it out based on the people’s profession and chemical text in workshop is reasonable. The last step, which is also the most difficult one, is to establish the relationship between asthma and work. Usually only a person’s history is not enough to confirm the diagnosis of occupational asthma, an objective test is preferred in the diagnosis process. A clear diagnosis is important not only for the medical care but also for the compensation purposes. There are several tools currently used in the diagnosis of occupational asthma. Specific inhalation challenge (SIC) is often considered as the gold standard, even though it has many limitations, such as the lack of availability [4] and the false negative and positive results[5]. The other alternative diagnostic techniques are to check history and questionnaires, serial lung function testing, non-specific bronchial provocation (NSBP) testing, immunological testing and measures of airway inflammation. Because this thesis doesn’t use these techniques, so the details about how to use and what the criteria are outside of the scope of this thesis.

Figure 1 Pathology of occupational agents

Pathology

The IgE-dependent mechanism is involved in the pathology of occupational asthma. The respiratory sensitizers, such as high-molecular-weight (HMW) and low-molecular-weight (LMW) agents are causal agents of occupational asthma. Antigen-presenting cells (APCs) can recognize HMW agents, and then escalate a CD4 type 2 immunologic response. The result of this response is that the B cells start to produce specific IgE antibodies with interleukin (IL)-4/IL-13. LMW could also induce the specific IgE antibodies, but in a different way. Like a haptens-protein, the LMW combines with a body protein and forms functional antigens. However, the LMW can not form the specific IgE antibodies directly. So the mixed CD4/CD8 type 2/type 1 immunologic response or stimulation of γ/δ-specific CD8 will help the LMW to shape it. If the high level of irritants is inhaled, the epithelium could be destroyed. Alarm signals from damaged epithelial cells activate immunocompetent cells. Because of that, Th2

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(IL-5) and Th1 (IFN-γ) cytokines, and other proinflammatory chemokine blinding of IgE, therefore, activate inflammatory cells. Mast cells, eosinophils and macrophages are responsible for the symptom of airway inflammation, such as airway hyperresponsiveness and airflow obstruction.[6]

Treatments for occupational asthma

Once OA is confirmed, there are several medical and non-medical treatment plans possible. The most common agreed approach is to remove the people from the workplace where the subjects are exposed to the sensitizer rather than using medication to control their symptoms.[7] The medical recommendation is similar to the non-occupational induced asthma. However, the lung function deterioration may still continue to the people who remain working in the same workplace, even when they take pharmacological treatment. Due to the financial reason that the people with occupational asthma might lose their job[8, 9] or lose part of the income when their job positions are changed from front line to the subsidiary positions, many people would prefer to stay in the same position. For the people who need to stay, the necessary approaches should be used to prevent or minimize the exposure to the sensitizer, such as using personal protection equipment, improving ventilation or to substitute the materials in process. The best way to control the progress of occupational asthma is to remove the people from sensitizer completely. This is considered to be the crucial step to coordinate with pharmacological therapy. Two groups of medications are introduced in management of occupational asthma: relievers (bronchodilators) and preventers (anti-inflammatory agents), which is similar to the management of non-occupational asthma [10]. Relievers are generally used to alleviate temporary breathing problems immediately, but are only a short-term solution. Examples of this kind of medications are salbutamol (Ventolin®) or terbutaline, long acting beta-agonists (LABA) such as salmeterol(Serevent®) and formoterol (Oxese®, Foradil®), and anticholinergic agents such as ipratropium bromide (Atrovent®) and tiotropium (Spiriva®). There is a study shows that these agents may protect the people from the drop in forced expiratory volume during work if these medication are taken before work. Preventers, often called “controllers” are used to reduce inflammation in the airways. This kind of medication needs to be used every day independent of the people are suffering the symptoms. Such medications are Corticosteroids, Combination agents inhaled corticosteroids and long acting beta-agonists, Advair® ,Seritide® , (Oxese®), Leukotriene receptor antagonists (LKTRA), Mast cell stabilizers, and Other agents(methylxanthines, antibiotics).[10]

Surveillance System

Surveillance system, usually considered as secondary prevention in a principle goal, is a very important component in the prevention of the occupational asthma. Reporting the diagnosis of occupational asthma in the surveillance system is a sentinel warning to the current workplace. Identifying the potential exposed people without delay is the key to prevent the morbidity and disability [11, 12]. Medical screening as well as exposure monitoring is the general

approach to surveillance programs[13, 14]. Medical departments normally carry out the medical

screening and the industrial hygiene professionals perform the exposure monitoring.

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Economics evaluation in health care

The different types of economics evaluation

The health economic evaluation are typically categorized into four groups: cost-minimization, cost-benefits, cost-effectiveness and cost-utility analysis[15]. The cost measurement in these four evaluations is similar; however the measurements of outcome are distinguished by the different approaches Cost-minimization analysis is based on the assumption that the outcome of the health intervention has the same consequence, so the comparison is only based on the costs.[15] In cost-benefits analysis, both costs and outcome are calculated in monetary units. To assign a value to benefits different tools can be used, such as willingness to pay. Willingness to pay is the monetary value people prefer to pay for the health intervention to gain some kind of benefit. If the monetary value of benefits is higher than the costs, it is considered as a good interventions or program[16]. Cost-effectiveness analysis use one-dimensional units, such as the cases prevented, as the outcome measurement and the monetary units in costs. The incremental cost-effectiveness ratio (ICER) is in general used in cost-effectiveness analysis. ICER is calculated as the ratio of the incremental difference in total costs to the incremental difference in effectiveness between programs. The effects of the incremental change reflects the effect from the treatment alternatives comparing to the next most effective programs.[15] Cost-utility analysis uses a standard outcome measure. This approach solves the problem that emerged in the cost-effectiveness analysis, the different programs and interventions are incomparable due to the various outcome measurements in cost-effectiveness analysis. With one of the most frequently used outcome measure tools- quality-adjusted life year (QALY), the cost-utility analysis can be used to compare the relative merits of many different types of health care programs. QALY is an index that weights the quality of life. It is calculated by multiplying the number of years gained from the health program with a utility value for the health status. Time trade-off, standard gamble and rating scale are the main approaches used

in measuring the utility values[17].

Cost

Estimating the costs is crucial in health economic evaluations and often conducted in different perspectives. The steps to calculate the costs start from identifying the costs components and the quantity in each. Each unit is matched with the suitable monetary value. The perspectives in estimating the costs are societal perspective, individual perspective, health care perspective, insurance perspective, company perspective and so on. The main perspective used is societal perspective. Every perspective has its own way to classify the costs group and costs components. For instance, the societal perspective implies that all costs, wherever it occurs, should be included in the analysis. This perspective is preferred by the majority of the researchers, since researches and studies done in the health economics field

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are more focused on the total social welfare. Apart from that the diseases usually have a wide impact on the society around the patient, which is hard to measure in any of the other perspectives. However, the other perspectives are used when the researchers and institute has their own interests. Costs are usually divided into three categorizes, direct costs, indirect costs and intangible costs[15]. When interventions affects the survival, the costs emerged in the increased life year should also be take in to account[18]. Direct cost means all the resources and services used in the process of cases seeking the health care, including direct medical costs and direct non-medical costs. The data on direct cost are usually collected for following cost categories: medication, hospitalization, doctor visit and the other (transportation, alternative treatment, referrals). Indirect costs, related to the productivity losses in society, are defined as the value of the output that is lost because people with a certain illness, disease or disorder are too impaired or too ill to work, either short-term or long-term[19]. Indirect costs are typically comprised of data on three main categorizes: Individuals (morbidity and quality of life), employer (labor turnover and cost sickness absence) and society (disability pensions and benefits). The leisure time of the patients and family members is also considered as a factor in indirect costs. Intangible costs are associated with pain, psychosocial suffering or the change of daily social activities. However, it is difficult to measure in the real setting and usually incorporated in the utility measurement. If the life expectance is prolonged by the health programs or interventions, there are several costs associated with this survival. From the societal perspective, the costs due to the increased production and consumption should be included in health economic evaluations[18]. The size of these costs is depending on the age of the subjects.

Costing

According to the basic economic theory, the resources should be valued in its opportunity cost. However, in reality, the opportunity costs are hard to measure and calculate. So the market value or accounting value is most commonly used in resource costing. However, for some items in costs, even market value is not available, such as informal health care provided by family or relatives. Several principles are used in costing this kind of items. One of them is to value the wage loss of the family or relatives [15]. The second way is to collect the payment information in case the care would be provided by a professional instead. The latter is also known as the replacement cost method[20]. Measuring the productivity loss is another concerned issue in health economic evaluations. There are two generic approaches used, human capital approach and friction methods. According to the friction method, productivity cost for long-term absence, disability and

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mortality mainly only occur during the time it takes to replace an employee[21], while assuming that in the long run the structural unemployment in the economy will provide an employee able to compensate for the lost potential from the injured employee[22]. The human capital methods take a long run approach, assuming the productivity lost capacity of the economics is reduced as a result, and unable to be compensated.

Cost of illness

A cost of illness study aims to estimate the economic burden of a specific disease brought to the whole society or to specific sectors. The assessment from cost of illness study will not give any guidance to how the resources should be allocated because it is not an effectiveness analysis, but to provide information for economic evaluation. There are two types of approaches used in cost of illness study: top-down or bottom-up. In the top-down approach, the national costs of disease are multiplied by the attributable risk of disease among all the other diseases to derive the overall cost burden of this specific disease. The advantage of the top-down method is that the calculation is easier compared to the bottom-up methods, and no extrapolation is needed. The problem with this method is that many costs will be underestimated, such as the social service and unpaid home health care. When the national registry system is not well constructed, the data is underreported. For instance, the short term leave due to illness is usually not recorded in the registration system. In the bottom-up approach, the cost data from individual patients with a specific disease are collected. The overall costs are extrapolated from the number of the patients with the costs of an individual patient. Cost of illness can be performed with either prevalence rate or incidence rate[23]. A prevalence based study estimate the costs emerged during a given period, regardless of when the disease has its onset. The advantage of a prevalence based study is that the annual cost of a certain disease can be measured and then compared to other diseases under the same time span. Incidence based study examines costs of a disease which develop for the first time. The overall costs including the production loss in future life are calculated in terms of the current value. It can be used to estimate the economic saving for the whole society when the specific diseases are prevented[24].

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2. JUSTIFICATION

In industrialized countries, the occupational asthma is the commonest occupational respiratory disease [25, 26], and it has caused a substantial loss in economic conditions to employees and society. One study showed 44% of occupational asthma cases had left their previous job, 25% were currently unemployed and 46% of the cases had suffered a reduction of income[27]. The consequence of occupational asthma is quite striking. Occupational asthma is a key component in all the asthma diseases. Several population-based studies suggest that hazardous occupation contribute about 10%-20% to the burden of adult asthma [28-35]. However, only a few studies have addresses its costs to the society and estimation of the figures are even fewer. One US-based study presents the annual cost of occupational asthma to be 1.6 billion US$[36]. In Europe, the total cost of asthma amounts to 17.7billion Euros per year. Lost productivity resulting from poor asthma controls is estimated at 9.8billion Euros per year[37]. Data collected from epidemiological studies are in widespread used for evidenced-based health economics research models. However, epidemiological data per se does not show any information about the cost of disease and itself is not a suitable parameter for policy maker to distribute the scarce health care resources and to rank public-health initiatives. So cost-of-illness studies are necessary information needed in order to compare published estimates for the same disease in other regions, or even other diseases.

The consequence of occupational asthma is quite striking. In Britain, there are 1500 to3000 cases are estimated to have work-related asthma annually by Health and Safety Executive[38]. In the United States, a prevalence of work-related asthma of 3.70% is reported in the Third National Health and Nutrition Survey, 1988–1994. In worldwide it is estimated that approximately 2% to 15% of all cases of asthma are occupational in origin. In rapidly developing countries, China and South Africa have similar population attributable fraction, 15% and 13% respectively[39, 40]. In less industrialized developing countries, population attributable fraction is low, such as 6% in Zambia[41]. Based on World Bank’s report, the occupational risk contribution to the worldwide asthma burden was about 38,000 deaths and about 1.6 million DALYs[42]. So, strategies to reduce the impact of occupational asthma therefore have the potential to yield substantial benefits.

3. AIMS

The primary objective of this study is to generate the best possible estimate of the cost of occupational asthma in Europe using a cost model incorporating suitable methods from prior studies, based on available literatures and databases. A secondary purpose is to discuss some shortcomings in present available epidemiological and economic data on occupational asthma.

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4. MATERIALS AND METHODS

Data materials

The data sets including the epidemiological data, cost data and demographic data were collected from previous literature, and national statistics were collected from Eurostat[43] and the European Central Bank[44]. Population-based epidemiological studies on occupational asthma are few and available mainly from western European countries. The search strategy included available electronic databases (Pubmed, Medline, Web of Science), and local sources were also included where the English abstract was provided, otherwise the original language was translated to English by the author. Incidence data was collected rather than prevalence data for calculating the economic benefits of reducing the number of new-onset cases since they are suitable for evaluating preventive measures[45]. This study was conducted with a societal perspective, so all the incurred costs were taken into account, regardless whom they accrue. This is preferred since occupational asthma is more related to the employment and labor market than the health care system. The impact of occupational disease is on the whole society. Cost data were derived from thirteen studies from different countries in Europe, and thus presented a comprehensive component breakdown of occupational asthma in a wide range of countries and health care systems. In the present study Europe is defined as the EU-27 countries plus Iceland, Norway, Switzerland, Bulgaria and Romania, so overall thirty-two countries are included. Other European countries have been excluded from this study, due to the fact that the necessary data was missing or difficult to access.

Incidence

12-month incidence rates were collected for occupational asthma by country. Where no data was available for the estimation, the mean of collected incidence rate were calculated. This procedure was used for computing purposes and it approximates occupational asthma

incidence by the average rate of surrounding countries and not by population attributable risk of occupational asthma for asthma which is used in a US-based study[36]. The summary of the review with original input data is provided in Table 1.

Direct costs

Direct costs are defined as all the resources and services used in the process of seeking health care. Data on direct cost included the following cost categories: medication, hospitalization, doctor visits as well as transportation, alternative treatment and referrals. Some other non-medical costs were ignored due to the limited information about these items, for

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instance, informal care and accommodations. That is, fixed cost elements like general administration and staff training are not included in the study.

Indirect costs

Indirect costs are defined as the value of the output that is lost because people with a certain illness, disease or disorder are impaired and too ill to work, either short-term or long-term[19]. In this study the human capital approach was applied. Indirect costs comprised data on three main categories: individuals (morbidity and mortality), employer (Labor turnover and costs for sickness absence) and society (disability pensions and benefits). Table 1 Incidence Input data in occupational asthma (12-month, cases per million workers) Country Year of

estimation Sample size Time frame Incidence

rate Source

Belgium 2000-2002 National surveillance program

2-year 23.5 Vandenplas O et al. [46]

Czech 2004 National surveillance program

1-year 14.7 Fenclová Z et al. [47]

Germany 2003 National surveillance program

1-year 51 Baur X et al. [48]

Spain 2006 National surveillance program

1-year 48.4 77.2 75.8

Orriols M R et al. [49]

France 2003 2002 1996-1999

National surveillance program

1-year 15 25.7

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Statistiques nationales [50] Kopferschmitt. K [51] Ameille J et al. [52]

Italy 1999 National surveillance program

1-year 24 Bena A et al. [53]

Poland 2003-2007 National Statistics

5-year 11 Wilczyńska Uet al. [54]

Portugal 2006 N/A N/A 17 APA. [55]

Romania 2007 N/A N/A 12.7 Adriana et al. [56]

Finland 1989-1995 National Registry

7-year 174 Karjalainen A et al. [57]

Sweden 1990-1992 National Registry

3-year 80 Torén. K [58]

United Kingdom

1989 National surveillance program

1-year 60 Meredith SK et al. [59]

Norway 2002 National Registry

N/A 115 Slåstad S et al. [60]

Switzerland 2007 National Registry

1-year 34.6 SUVA [61]

Note: Estimates for the other countries were based on the extrapolation from above available data.

The intangible costs, which include pain, psychosocial suffering and changes in social

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functioning and activities of daily living, are valued in the quality of life (QoL). Not all the studies estimated indirect cost due to occupational asthma. Data was only available in eight countries. Cost data for employer and society were mostly based on one UK study[62] and one Swedish Study[63]. All economic input data used in estimations are summarized in Table 8.

Costing model

The cost model used for evaluating the economic burden of occupational asthma was based on a model developed in a previous study for assessing the cost of depression [64]. The model was used to predict results for countries where the data were unavailable in the literature. The time frame and growth rate for costs due to the time frame[62] were considered in the present model. The different stages in the model were used to simulate the cost of occupational disease based on the analysis of employment related cost and other indirect cost in life circle. The current study is mainly based on the bottom-up approach, where the cost data are collected per case and the data from the sample are aggregated to national levels based on incidence data. The model include following 5 steps: Step 1: The collected cost data was in different currencies in different years. In order to compare the cost to the same year with the same value, the original currencies were transformed to Euros in the year the original studies performed, based on the historical exchange currency rate[65]. Since the year chosen for the study is 2008, all these value were transformed to 2008 by Harmonized indices of consumer prices (HICP,1992-2008)[66], which is an aggregate measure of the increase in the consumer prices for a predefined collection of goods and services in the specific country. Step 2: For the countries where data was not available, the arithmetic mean of all existing data was imputed to form the basis for the simulation. The direct cost and indirect cost were adjusted with different indexes to eliminate the price level differences in the different countries across Europe. All direct costs (in Model 1, below) were adjusted with Comparative Price Level which provides a measure of the differences in price levels between countries by indicating for a given product group the number of units of the common currency needed to buy the same volume of the product group in each country[67], and was simulated in a total life time frame. Indirect costs (in Model 2, below) were adjusted with an index of wage level differences based on purchasing power parity (PPP) in Europe and Comparative Price Level. The Morbidity and cost for sickness absence were simulated in the employment time frame with an index income increase rate. The quality of life was simulated in total life time frame with an index income increase rate. The societal cost was simulated in total life time frame with an index of disability pensions and benefits increase rate. The time frame impact was ignored in labor turnover and mortality that were considered as one-off cost. The description of the time frame and rates used is in below. Step 3: The number of possible occupational asthma cases was calculated from the incidence rate and the total number of employees by countries. The total cost per case was combined from direct cost and indirect cost after adjustments. The total cost per nation was calculated to estimate the whole cost of occupational asthma in Europe.

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Table 2 Cost Input data in occupational asthma

Country Year of

estimation

Sample size Time

frame

Cost include Direct cost Indirect

cost

Source Currency

Denmark 2000 Based on estimate

of 0.3 million

N/A Direct cost and

indirect cost

3983 2823.3 Mossing R et al. [68] DKK

Estonia 1997 1423 1-year Direct cost 118 N/A Kiivet Ra et al. [69] EUR

Finland 2003 Based on National

Programme

10-year Direct cost 1031 N/A Haahtela T et al. [70] EUR

France 1999 N=282 2-year Direct cost and

indirect cost

1270 297 Van Ganse E et al.

[71]

EUR

Hungary 1999 N=711 0.5-year Direct cost and

indirect cost

499 133 Herjavecz I NG et al.

[72]

EUR

Italy 1999 N=500 0.5-year Direct cost and

indirect cost

600 660 Antonicelli L et al.

[73]

EUR

Netherlands 1993 N/A 1-year Direct cost 499 N/A Rutten-van Mölken

MP et al. [74]

USD

Spain 1992 N=385 1-year Direct cost and

indirect cost

885 1993 Serra-Batlles J et al.

[75]

USD

Sweden 1996 N=115 1-year Direct cost and

indirect cost

4931 10988 Jansson S-A et al.

[63]

SEK

United

Kingdom

2003 N/A 1-year Direct cost and

indirect cost

622.5 5253 Boyd R et al.

[76]

GBP

Norway 1995 N=78 1-year Direct cost and

indirect cost

4718 11900 Gallefoss F et al.

[77]

NOK

Switzerland 1997 N=589 1-year Direct cost and

indirect cost

1778 1264 Szucs T et al.

[78]

CHF

Turkey 2001 N=118 1-year Direct cost 1465.7 N/A Celik GE et al.

[79]

USD

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Time frame

The total life time costs were calculated since the incidence rate is used to estimate all additional costs to the society. The average age of the occupational asthma is assumed to be 40-year old[80]. The average age of retirement is considered to be 63-year old, so 23 years are left till retirement. The average life-expectancy is assumed to be 78-year old[81], that is 38 year left till the end of life.

Rates

All cost components related to direct cost grow in real terms at 3.3% per annum based on HICP Health inflation rate [43]. All cost components relating to the income and employment increase in real terms at 4.2% per annum (1998-2008, 11 year’s average in Europe 27). The disability pensions and benefits are assumed to increase in real term at 1.8 per annum (1996-2006, 11 year’s average in Europe 15). All of these rates were in line with past trends [43]. Model for calculating the direct cost:

Direct cost = ∑=

=

−− ++Lt

xnt

nLm

nLHscds DrCCM

)(

)()( )1/()1)(/( (Model 1)

Where L is the life of expectancy, x is the age of cases with occupational asthma, n >= 40. Mds is the average for the direct cost in selected countries. Cc is the consumer price index for estimated countries and Cs is the CPI for average of the selected countries. rH is the HICP, health inflation rate. Dm is the discounting rate of monetary value. Here selected countries mean the countries with available original data. Model for calculating the indirect cost:

Indirect cost = ∑=

=

−− ++Rt

xnt

nRm

nRIssccimcs DrCICIM

)(

)()( )1/()1)(/(

+ ∑=

=

−− ++Lt

xnt

nLq

nLIsscciq DrCICIM

)(

)()( )1/()1)(/( (Model 2)

+ ∑=

=

−− ++Lt

xnt

nLm

nLDssccid DrCICIM

)(

)()( )1/()1)(/(

R is defined as the time of retirement. Mimcs is the average for the morbidity and cost of sickness absence in selected countries. Miq is the average cost of QoL in selected countries. Mid is the average cost of the disability pension and benefits in selected countries. Ic is the Income level in estimated countries and Is is the average income in selected countries. rI is the income increasing rate and rD is the disability pensions and benefits increasing rate. Dq is the discounting rate of QoL.

20

Discounting

In accordance with National Institute of Health and Clinical Excellence (NICE) guidance, QoL was discounted at a rate of 3.5% per year[82]. The discounting rate for monetary units was 5% per year[83].

Analysis tools

MS Excel version 2003 (Microsoft Inc., USA) was used to analyze the data, including the cost estimation and sensitivity analysis.

Sensitivity analysis

Internal validity and external validity were tested in the model. The main sources of variation in the input of the model were tested. The uncertain source weights are identified on the study’s conclusion. The final cost estimates were compared with previous cost estimates in asthma and occupational asthma both in European countries and North American countries.

21

5. RESULTS

Incidence of the occupational asthma

Incidence rate is available in 14 countries. The total number of new cases with occupational asthma in Europe amounted to 11 thousands in the employment groups in 2008. Large variations in the incidence rate of occupational asthma were found among different European countries. The selected and estimated incidence rates in this study are presented in Figure 2, ranged from 174 till 11 cases per million employees. It shows an average incidence of occupational asthma of 50.48 per million in the analyzed population.

Figure 2 Incidence Rates of Occupational asthma in European Countries Figure 3 illustrates that the high incidence rates are mainly concentrated in highly industrialized countries, for instance the Nordic countries, Spain, UK and Germany, and the lowest are in Eastern Europe countries, such as Poland, Romania and The Czech Republic. The estimated total number of cases with occupational asthma in the different countries range from 2,333 in United Kingdom and less than 10 in Hungary and The Czech Republic.

22

Figure 3 Distribution of Incidence Rate of Occupational asthma in Europe

Cost per case by country

Figure 4 shows the estimated costs per case of both direct cost and indirect cost by countries in Europe. The cost per case differs significantly across Europe, ranging from €259,568 to €17,911. The result shows that the case in high income countries has a high cost of occupational asthma. In the high income countries, the indirect cost is higher than the direct cost, and the direct cost is close or even higher than the indirect cost in the countries with PPP adjusted wage per capita lower than €13,000 and EU admission countries. The total cost per case of occupational asthma was estimated to be fourteen times higher in the highest countries than in the lowest countries.

23

0 50,000 100,000 150,000 200,000 250,000 300,000

Luxembourg

Iceland

United Kingdom

Norway

Switzerland

Ireland

Denmark

Finland

France

Belgium

Austria

Netherlands

Germany

Italy

Spain

Turkey

Sweden

Cyprus

Greece

Slovenia

Portugal

Malta

Croatia

Czech

Latvia

Hungary

Slovakia

Lithuania

Poland

Romania

Estonia

Bulgaria

Cost per person (Unit:€, 2008)

Total cost

Indirect cost

Direct cost

Figure 4 Cost per Case with Occupational asthma in Europe in 2008

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Cost for occupational asthma

The total cost of occupational asthma was estimated at 1.2 billion in 2008 in Europe. The indirect cost is the single most dominant cost category. The total cost of occupational asthma is unevenly distributed across European countries in absolute terms (see Table 9). The United Kingdom, Germany and Spain make up 55% of the total cost of occupational asthma, where as they hold 35% of the employees in Europe. Moreover, the cost of occupational asthma varies substantially from one European country to another, for instance €352 million in United Kingdom and less than half million in Malta. The major reasons for these variations lie in different number of employees, the cost per case and the incidence rate.

Cost of occupational asthma distributed by resource category

The distribution of the annual new cost of occupational asthma in Europe on different components is presented in Figure 5. The impact of indirect cost (i.e. cost of morbidity, mortality, labor turnover, sickness absence, disability pensions and benefits) on total cost is substantial amounted to €862 million, corresponding to 72% of the total cost. Cost to individual and social pensions is the dominating indirect cost, reaching €794 million in 2008 (66% of the total cost and 92% of the indirect cost). The direct cost was estimated to €335 million, accounting for the 28% of the total cost. The bulk of the direct cost is due to Medication, €175 million (52% of the direct cost).The hospitalization and the other costs(i.e. transportation, alternative treatment, referrals) amounted to 123 million (37% of the direct cost).

Figure 5 Distribution of Cost of Occupational asthma in Europe by Resource Category

25

Table 3 Cost of Occupational Asthma by country (€PPP million, 2008)

Direct

costs

Indirect

costs

Total

costs

Medication Non-Medication Individual Employer Social

Belgium 1.6 1.5 3.5 0.9 4.6 12.1

Bulgaria 1.2 1.1 0.3 0.06 0.4 3.0

Czech Rep 0.7 0.7 0.5 0.1 0.7 2.8

Denmark 1.5 1.0 5.4 2.1 11.3 21.4

Germany 28.6 27.4 54.6 13.3 70.7 194.5

Estonia 0.07 0.2 0.3 0.06 0.3 1.0

Ireland 1.9 1.8 5.1 1.2 6.5 16.5

Greece 3.0 2.9 3.3 0.8 4.2 14.2

Spain 17.6 21.4 26.7 6.5 34.5 106.7

France 16.4 10.7 12.8 4.5 23.9 68.3

Italy 3.8 10.3 15.2 3.1 16.2 48.6

Cyprus 0.2 0.2 0.3 0.07 0.4 1.2

Latvia 0.6 0.6 0.4 0.09 0.5 2.1

Lithuania 0.7 0.7 0.4 0.1 0.5 2.4

Luxembourg 0.2 0.2 0.1 0.2 1.2 2.7

Hungary 1.9 2.1 1.3 0.4 1.9 7.6

Malta 0.09 0.08 0.09 0.02 0.1 0.4

Netherlands 6.2 6.0 12.5 3.0 16.1 43.8

Austria 3.0 2.9 6.1 1.5 7.9 21.4

Poland 1.7 1.6 0.8 0.2 1.1 5.4

Portugal 1.1 1.0 1.0 0.2 1.3 4.7

Romania 1.0 1.0 0.4 0.08 0.5 2.9

Slovenia 0.6 0.6 0.7 0.2 0.9 3.0

Slovakia 1.2 1.1 0.7 0.2 0.9 4.1

Finland 5.2 9.0 16.4 4.0 21.3 55.9

Sweden 4.0 5.0 8.5 3.2 9.7 30.3

UK 16.4 32.2 192.0 12.4 99.1 352.0

Croatia 0.6 0.6 0.6 0.1 0.7 2.7

Turkey 47.2 11.0 10.5 2.6 13.5 84.8

Iceland 0.1 0.1 0.6 0.2 0.8 1.9

Norway 4.5 1.9 20.0 4.0 22.8 53.5

Switzerland 2.3 3.3 6.8 2.0 10.6 25.0

Europe 175.1 151.9 408.5 67.7 385.4 1,196.7

Note: The total number will not exactly equal to the summation of its components due to the

rounding.

26

Sensitivity analysis

Incidence rate and all input cost were put to the test. The data on incidence rate and cost used in the cost estimation were varied by 10%. The total cost of occupational asthma varied from €0.97 billion to €1.45 billion. Different ways of testing the variables were used in the sensitivity analysis. In a one-way sensitivity analysis, the total cost ranged from € 1.08 billion to € 1.32 billion when incidence rate and estimated cost was tested respectively. In a two-way sensitivity analysis, the incidence rate and estimated cost were simultaneously tested over 10% ranges, and the cost varied from €0.97 billion to €1.45 billion.

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6. DISCUSSION

The results from the present study show that occupational asthma causes a substantial economic burden to both health care system, as well as the whole society. The underlying reason for this significant cost of occupational asthma lies in the markedly high indirect costs due to morbidity of employees and social disablement pensions and benefits. Despite our high estimates of the cost of occupational asthma, we are likely underrating the real economic burden of occupational asthma in Europe. Compared to the study in cost of occupational asthma in USA ($1.6billion, 136million employees, 2002)[36], the cost of occupational asthma among 222 million European employees in the present study is also probably underestimated because the illegal immigrants is not included. Based on this, it is expected that our current cost estimates of occupational asthma in Europe are quite conservative. Firstly, this is particularly the case because incidence data from major countries based on the national surveillance system or self-report registry system are incapable of recording all the occupational asthma cases, namely the undiagnosed and unrecognized occupational asthma, for instance the self-employed are likely to be under-represented on the disease register. Secondly, we restrict the study to use incidence of occupational asthma only, not the population attributable risk (PAR) of asthma to occupational factors, since the PAR of asthma due to occupational factors is very high in studies ranging from 10% to 20%, with a median value of 15%[28]. Hence, if 15% were treated we would see a dramatic increase in overall costs. One recent study has suggested an incidence rate of 250–300 cases per million people per year with the model of population-attributable risk around 15% for adult asthma due to occupational exposures[84]. Using this estimated incidence rate in the present model, the new-onset occupational asthma cases will range from 63,000 to 75,000 and the total cost will range from €6.2 billion to € 7.4 billion. Thirdly, since occupational asthma is rarely fatal, its prevalence will therefore be considerably greater than its incidence[85], means the number of cases with direct cost and indirect cost would heighten. There are no recent studies calculating the cost of occupational asthma in Europe with a bottom-up approach. One paper estimating the cost of occupational asthma in Europe reached an overall cost of €0.4-0.8 billion in 2003 [86], as compared to our estimate for 2008 at €1.2 billion. It is, however, difficult to give more detailed interpretation since little information was provided on the details of their calculations. Since the overall estimation of cost of occupational asthma in Europe is unavailable, the studies with cost of occupational asthma were compared with a non-Europe study. Within the comparison of the direct cost, the drug costs of occupational asthma constitute 52% of the direct cost, which is in agreement with recent cost of illness studies [87]. The present study shows that indirect costs of occupational asthma constitute 72% of the overall cost of occupational asthma in 2008, which is in disagreement with previous cost of illness studies 12% in USA[88] and 32% in Australia[89]. The reasons for the opposite outcome in these two studies are likely due to the lack of analysis in overall cost related to employment, social disablement pensions and benefits and the cost of life circle. In the present study, given the high incidence, the high persistence and chronic nature, occupational asthma should be expected to have very high indirect costs and a substantial burden of illness measures.

28

Studies are rarely seen estimating the cost associated which disablement benefits and disability pensions caused by occupational asthma[62, 63]. We reached a conservative estimate of disablement costs of occupational asthma in Europe at €385 million, thus exceeding the direct treatment costs (€335 million). Disablement costs have previously been estimated in a USA study for asthma to employer, among asthmatic employees with disability claims. Total costs were approximately 3 times higher than those in the employee control group[90]. By comparing cost per case, in nine out of thirty-two countries(Turkey, Hungary, Czech, Latvia et al.), the direct cost is the same or higher than the indirect cost (Figure 2). One reason for a similar feature of these countries is that the wage/capital ratio is less than €13,000(total ten countries out of thirty-two). The reason for this might be due to the low indirect cost since the social disablement pension and labor cost is relatively low in the domestic market. However, the price of medication is somewhat close to those of the international market. The conclusion is that direct costs in all countries are close to the same level. The current study has presented the cost of occupational asthma in Europe in 2008. The burden is huge not only for the employees but also for the society as a whole. And among the cases, only a minority of all people could identify the allergen at the first exposition time so that they have an opportunity to seek help for their work environment and get medical attention adequately[85]. Previous studies have shown that quick and early-controlled treatment of asthma may not only lead to substantial cost savings as the case returns to their work, but also in terms of fewer health care visits both in the short term, as well as long term[91, 92]. Potential annual cost savings on the level of €1.2 billion is a strong justification for public investment in research to help in its prevention. Current data suggest the expenses for prevention from 1% in Denmark to 6.5% in Germany[93] as a proportion of the total cost of occupational disease in European countries. Furthermore, besides better identification, quantification of incidence cases and the costing of resource utilization in occupational asthma in Europe, the main challenge for the future lies in further improvement of occupational respiratory disease surveillance systems both on the production level and on the regional and national levels, e.g. through optimizing the detection of hazards. It is essential for future research to better evaluate the possible available approaches for reducing the cases of occupational asthma, to use the available resources in the most efficient way, and to be able to halt the increasing cost of occupational asthma to the society.

29

7. LIMITATIONS

Although a cost estimation model provides a useful tool for evaluating overall cost of occupational asthma in Europe, certain methodological limitations must be pointed out. First, well-designed randomized controlled trials that directly measure the incidence rate of occupational asthma are extremely scarce. This lack of direct evidence suggests the use of cost modeling methods that combine data from a variety of sources including epidemiological data, cost data and national statistics to estimate epidemiological outcomes and related costs. These estimates, which are based on a series of postulations, may or may not accurately imitate true costs and benefits. Other limitations relate to the generalizability of a specific analysis to estimate indirect costs that were incapable to record from a majority of EU countries. The main sources for this estimate only came from United Kingdom and Sweden where the industrialization degree and economic status are comparatively better than certain other countries in the study. Clearly, the results extracted from these two countries may not be appropriate to other populations, practice settings, or time horizons. A third limitation concerns the inability to measure direct non-medical data accurately. Epidemiological data in eastern and southern Europe is largely of low quality. This fact may limit the validity of cost modeling in general, and cost estimation in particular. The limited data in incidence rate for some countries is the challenge for author to do an overall economic estimation for the European countries. Using mean of the available countries to simulate the countries where the incidence rate is lack could cause either over- or underestimation in some extent. But when the other costs data available, it is still helpful to use arithmetic mean in the model to generate the estimation of the economic burden. If use median to simulate the others, the result from this study looks like overestimate the economics burden of occupational asthma. However, the high incidence rate is reported in the country where the national surveillance system is founded longer than the other low incidence rate reported country. If we assume the quality of national surveillance system is improving every year, especially in the Western Europe, it is reasonable to put more weight in the incidence rate collected in these countries, so using mean is more suitable than median to simulate. With these limitations in mind, the core outcome of the inquiry is primarily that we need more and better studies to allow for substantive cost analyses in the future. There is only a handful of cost-of-illness studies conducted in the area to date, and they are all based on direct medical cost (i.e. drugs, physician contact and hospitalization). Despite these limitations, cost estimate models offer a unique mean to generate insights into the costs analysis associated with epidemiological data.

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8. CONCLUSION

Proper treatment of occupational asthma is not costly, but not treating occupational asthma properly is very costly. This study has addressed the economic magnitude of occupational asthma in Europe and has emphasized the severe economic burden for society and for individuals. The total cost of occupational asthma was estimated at 1.2 billion in 2008 in Europe for thirty-two countries. The cost per case differs significantly across Europe from country to country. The costs data underscores important facts: hospitalization and medications have been found to be the most important cost driver of direct costs, while individual and social pensions accounted for the greatest percentage of indirect costs. Until now, very little economic information concerning costs of occupational asthma is available in the literature today. Studies of the economic burden of illness have been conducted in only a few developed countries in Western Europe. Employers who are most impacted group present the most important assets for countries. In order to encourage the factories and companies to take steps in controlling occupational asthma and decreasing its costs to society, alternative funds can be created so as to contribute to financing quantity and quality treatment, supervision and research in industry hygiene facilities. Furthermore, occupational cases and suspected cases in production frontline and occupational clinics has to be overseen and controlled since there seems to be some sort of underreport in surveillance. Finally, all those involved in occupational asthma care need to be aware of what drives costs. Economic studies demonstrate that occupational asthma is a very costly disease and that interventions used to prevent and control occupational asthma usually differ greatly in terms of costs per health outcome gained. Health providers and policy makers should use this information in making clinical and policy decisions in order to allocate resources efficiently.

31

ACKNOWLEDGEMENTS I would like to express my sincere gratitude to the following people, who have all contributed

to making this thesis and contributed during my two year study period at the Umea

University’s Department of Public Health and Clinical Medicine, or in the other way made life

enjoyable and tolerable during the time I have worked on this thesis.

Håkan Brodin, my supervisor, for his valuable contribution and guidance to this thesis.

All the staff of the Department of Epidemiology and Public health, for their excellent support

in academic, administrative and other activities during the study periods.

Friends and colleagues at 2008-2010 Umea International School of Public Health, for all

joyful at work and outside work.

Janna Maria Brouwer for her skillful and rapid revision of my Chinglish.

My dear friends and everlasting colleague, Stefanie Butz and Bruno Guerreiro Semedo, for

endless inspiration, talks and moments of Weekend Fika.

Special thanks to Shabnam Salimi and Na Guan who contributed with searching the

inaccessible papers around the world.

My dear wife, Meng, my most important support in life, for your never ending love, being

caring and patient with me in both good times and bad times.

32

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10. APPENDIXES

37

APPENDIX I. Currency rate in this article

Date Rate

2001-12-31 December 31, Monday 1 DKK = 0.134501 EUR, 0.13

1993-12-29 December 29, Wednesday 1 USD = 0.888888 EUR, 0.89

1992-12-31 December 31, Thursday 1 USD = 0.830564 EUR, 0.83

1994-12-30 December 30, Friday 1 SEK = 0.109733 EUR, 0.11

2003-12-31 December 31, Wednesday 1 GBP = 1.41637 EUR, 1.42

1996-12-31 December 31, Tuesday 1 NOK = 0.12504 EUR, 0.13

1997-12-31 December 31, Wednesday 1 CHF = 0.623372 EUR, 0.62

2001-12-31 December 31, Monday 1 USD = 1.12347 EUR, 1.12

Source: X-rate, the historical exchange rate, http://www.x-rates.com/cgi-bin/hlookup.cgi

APPENDIX II. Harmonized indices of consumer prices

Year, Month Value Same 1 EUR buying power in 2008

Year value Same 1 EUR buying power in 2008

1992,Dec 77.25 1.39 2000,Dec 90.74 1.19 1993,Dec 79.02 1.36 2001,Dec 92.54 1.16 1995,Dec 83.65 1.29 2003,Dec 96.50 1.11 1996,Dec 85.29 1.26 2005,Dec 100.88 1.07 1997,Dec 86.55 1.24 2008,Dec 107.57 1.00 1999,Dec 88.61 1.21 Source: European Central Bank, Harmonized indices of consumer prices (HICP), http://sdw.ecb.europa.eu/home.do. Access DATA2009-08-04.

38

APPENDIX VIII. Statistics data in Europe used in this thesis

Employees GDP(€PPP) GDP

/capita Gross wage* Gross wage

/capita Health expenditure

Health expenditure/ capita

Comparative Population statistics

2008(10*3) (106), 2008 (€PPP) (€PPP) (106) (€PPP) (€PPP) (106) 2007

(€PPP) price level in 2008**

Country

2007 2008

EU-27 495090294 497659814 221762.5 12,505,075.00 25,127.76 4,791,229.00 21,605.23 976,815.00 1,973.00 100

Belgium 10584534 10666866 4445.9 344,206.00 32,268.71 130,850.00 29,431.61 28,117.00 2,656.42 110.7

Bulgaria 7679290 7640238 3360.7 66,728.00 8,733.76 10,179.30 3,028.92 3,463.00 450.95 51

Czech Republic

10287189 10381130 5002.5

3,705,868.00 356,981.18 49,755.50

9,946.13 230,357.00 22,392.61 72.4

Denmark 5447084 5472093 2853.8 1,739,716.00 317,925.15 118,833.60 41,640.48 135,777.00 24,926.55 141

Germany 82314906 82217837 38879.7 2,491,400.00 30,302.43 994,070.00 25,567.84 206,014.00 2,502.75 103.9

Estonia 1342409 1340935 656.5 248,149.00 185,056.70 6,444.30 9,816.15 12,457.00 9,279.59 76.7

Ireland 4312526 4401335 2101.2 185,721.00 42,196.52 76,143.40 36,238.05 14,721.00 3,413.54 126.9

Greece 11171740 11213785 4559.4 242,946.00 21,664.94 66,468.60 14,578.37 15,280.00 1,367.74 94.1

Spain 44474631 45283259 20257.6 1,095,163.00 24,184.72 401,135.00 19,801.70 77,455.00 1,741.55 95.7

France 63392140 63983000 26004 1,950,085.00 30,478.17 743,316.00 28,584.68 163,288.00 2,575.84 111.1

Italy 59131287 59619290 23404.7 1,572,243.00 26,371.38 479,258.20 20,477.01 128,578.00 2,174.45 105.3

Cyprus 778684 789269 382.9 16,949.00 21,474.30 6,383.80 16,672.24 779.00 1,000.41 89.6

Latvia 2281305 2270894 1124.5 16,243.00 7,152.69 9,738.90 8,660.65 712.00 312.10 74.7

Lithuania 3384879 3366357 1520 111,499.00 33,121.56 11,635.30 7,654.80 6,432.00 1,900.22 66.8

Luxembourg 476187 483799 202.4 36,662.00 75,779.40 15,100.00 74,604.74 1,588.00 3,334.82 116.2

Hungary 10066158 10045401 3879.4 26,620,504.00 2,650,019.05 40,735.60 10,500.49 1,668,258.00 165,729.37 69.7

Malta 407810 410290 160.3 5,759.00 14,036.41 2,246.30 14,013.10 341.00 836.17 78.4

Netherlands 16357992 16405399 8592.7 594,608.00 36,244.65 230,569.00 26,833.13 36,302.00 2,219.22 103.4

Austria 8298923 8318592 4089.9 282,286.00 33,934.35 112,020.90 27,389.64 17,975.00 2,165.94 104.6

Poland 38125479 38115641 15799.8 1,271,715.00 33,364.65 106,525.90 6,742.23 74,862.00 1,963.57 68.6

Portugal 10599095 10617575 5197.8 166,228.00 15,655.93 64,621.64 12,432.50 16,474.00 1,554.28 86.7

Romania 21565119 21528627 9369.1 503,959.00 23,408.78 44,409.81 4,740.03 21,229.00 984.41 62.1

39

Employees GDP(€PPP) GDP /capita

Gross wage* Gross wage /capita

Health expenditure

Health expenditure/ capita

Comparative Population statistics

2008(10*3) (106), 2008 (€PPP) (€PPP) (106) (€PPP) (€PPP) (106) 2007

(€PPP) price level in 2008**

Country (Cont.)

2007 2008

Slovenia 2010377 2010269 996.1 37,126.00 18,468.18 16,531.00 16,595.72 2,351.00 1,169.43 83

Slovakia 5393637 5400998 2433.7 67,331.00 12,466.40 18,865.40 7,751.74 4,010.00 743.47 69.5

Finland 5276955 5300484 2530.9 186,164.00 35,122.08 73,136.00 28,897.23 13,797.00 2,614.58 124.6

Sweden 9113257 9182927 4593 3,156,881.00 343,777.21 136,320.60 29,680.08 240,126.00 26,349.09 114.4

UK 60816701 61193524 29363.9 1,442,921.00 23,579.64 819,905.10 27,922.21 109,121.00 1,794.26 99.4 Croatia 4441238 4436401 1227.3 342,159.00 77,125.35 14,176.48 11,550.95 27,156.00 6,114.51 74.7

Turkey 69689256 70586256 21565.6 950,144.00 13,460.75 N/A 12736.8 49,279.00 707.12 72.8

Iceland 307672 315459 177.1 1,440,264.00 4,565,613.91 N/A 57694.93 111,019.00 360,835.57 117.3

Norway 4681134 4737171 2513.7 2,548,322.00 537,941.74 106,377.30 42,319.01 166,243.00 35,513.40 139.1

Switzerland 7508739 7593494 4228.8 532,149.00 70,079.60 175,671.30 41,541.64 42,840.00 5,705.35 130.4

Source: Eurostat, http://ec.europa.eu/eurostat