The burden and cost of cancer

18 (Supplement 3): iii8 iii22, 2007 doi:10.1093/annonc/mdm097 The burden and cost of cancer summary The incidence of cancer is increasing and the reasons for this are multifactorial. With respect to mortality, there have been improvements and some countries have seen a plateauing of mortality rates. However, cancer still currently accounts for 7 million deaths annually worldwide. Cancer accounted for 16.7% of all healthyõ years lost in European Union (EU) 25 in 2002 and 12.5% of all healthyõ years lost in United States and Canada. However, the share of health care expenditure allocated to cancer is significantly lower than the share of the burden of the disease. Indirect costs accounts for more than two-thirds of the costs of cancer. Direct health care costs account for 7% of the total health care costs. Cost for cancer drugs account for 13% of all health care costs for cancer and 5% of total drug costs. cancer incidence and mortality Differences in the burden of cancer between different countries relates to cancer incidence, cancer mortality and prevalence of individuals with cancer. Cancer incidence is defined as the number of new cases in a defined population over a specific time period. Cancer prevalence represents the disease burden in a population at a specific time and is related to survival of individuals diagnosed with cancer. In 2002, there were an estimated 11 million new cancer cases reported worldwide with 7 million cancer deaths. Out of these new cancer cases, 45% occurred in Asia, 26% in Europe, 15% in North America, 7% in Central/South America, 6% in Africa and 1% in Oceania. The most common malignancies were lung, breast, colorectal and stomach cancer followed by prostate and liver cancer. Mortality from cancer is second only to mortality from cardiovascular diseases, and in 2004 1.7 million individuals, only in Europe, died from the disease. The highest mortality from cancer was seen for lung, stomach and colorectal cancer [1, 2]. Even if the population, like in Europe, has been stable for a number of years and is anticipated to remain so for the years to come, there has been a steady increase in the number of new cancer cases. The ageing of the population means that overall cancer incidence will increase. For example, during the period 1963 1997, there was 50% increase in the overall incidence of all cancers (excluding nonmelanoma skin cancer) in Europe, with little or no difference between the constituent countries. The increased incidence is not totally explained by an ageing population. Other nonmodifiable factors such as genetic susceptibility most likely play an important role. Lifestyle factors, such as increasing prevalence of female smokers, change of suntanning habits and lower rates of reproduction, also all contribute to an increase in the incidence of cancer. The International Agency for Research on Cancer provides the most current data on the incidence of, and mortality due to, cancer (with incidence data to 1997 and mortality data to 2002) [3]. These data are expressed as an age-standardised rateõ; this is a summary measure of a rate that a population would have if it had a standard age structure and, as age has such a powerful influence on the risk of cancer, is necessary when comparing several populations that differ with respect to age. The most frequently used standard incidence is called the world age-standardised rate, which is expressed per 100 000. It is likely that a number of factors influence the difference in the registered mortality rates, particularly population-based cancer registration, mandatory reporting, the quality of cause-of-death registration, access to screening and health care and differences in management between countries. the burden of cancer Measures of the burden of disease are a complement to statistics about the incidence and prevalence of disease, most often used for health policy purposes. One example is the report published during the Dutch Presidency of the EU in the second half of 2004, focusing on priorities for medicines research [4]. The most commonly used measure of the burden of cancer is disability adjusted life yearsõ (DALYs). This is an integrated measure of mortality and disability developed by the World Health Organisation and the World Bank. One DALY can be thought of as one lost year of healthyõ life and the burden of disease as a measurement of the gap between actual health status and an ideal situation where everyone lives into old age free of disease and disability. As shown in Table 1, in 2002, cancer accounted for close to 10 million DALYs lost in the EU 25 and >5.7 million DALYs lost in the Unite States and Canada. Cancer represented 16.7% and 12.5%, respectively, of all DALYs lost in the EU 25 and United States and Canada, thus cancer was the third most prominent disease in terms of overall disease burden, following mental illnesses and cardiovascular disease in these regions. In Japan, Australia and New Zealand, cancer was second after mental diseases in proportion of DALYs lost [5]. The proportions of years of life lost (YLL) and years lost due to disability of ª 2007 European Society for Medical Oncology

Table 1. Top five disease groups in terms of burden of disease in the selected countries/groups of countries in 2002 [5] EU 25 EU 15 United States and Canada Total DALYs DALY/1000 % Total DALYs DALY/1000 % Total DALYs DALY/1000 % All disease groups 58 807 846 129.7 100.0 47 092 868 124.2 100.0 45 213 504 140.3 100.0 Mental disease 14 857 720 32.8 25.3 12 379 282 32.7 26.3 13 484 719 41.8 29.8 Cardiovascular disease 10 088 093 22.2 17.1 7 637 493 20.1 16.2 6 616 765 20.5 14.6 Cancer 9 839 035 21.7 16.7 7 989 864 21.1 16.9 5 658 112 17.6 12.5 Injuries 5 099 011 11.2 8.7 3 644 620 9.6 7.7 4 338 436 13.5 9.6 Respiratory disease 3 523 243 7.8 5.9 3 167 675 8.4 6.7 3 167 067 9.8 7.0 Japan Australia and New Zealand South Africa Total DALYs DALY/1000 % Total DALYs DALY/1000 % Total DALYs DALY/1000 % All disease groups 13 296 210 104.3 100.0 2 605 580 111.4 100.0 20 560 460 459.4 100.0 Mental disease 2 986 128 23.4 22.5 713 065 30.5 27.4 1 394 840 31.2 6.8 Cardiovascular disease 2 155 604 16.9 16.2 333 573 14.3 12.8 958 267 21.4 4.7 Cancer 2 361 394 18.5 17.8 373 114 16.0 14.3 459 145 10.3 2.2 Injuries 1 341 082 10.5 10.1 254 168 10.9 9.8 1 744 778 39.0 8.5 Respiratory disease 750 146 5.9 5.6 296 378 12.7 11.4 419 464 9.4 2.0 DALY, disability adjusted life years. a DALY vary considerable depending on disease group; for cancer, YLL represent >90% of the DALYs lost in Europe, YLL represent 70% 90% of DALYs lost for mental disease, cardiovascular disease and injuries, whereas for respiratory disease YLL represent <40% of DALYs lost. the costs of cancer The costs to society of cancer can be divided into direct and indirect costs: Direct costs are the resources used for prevention, treatment, etc. Indirect costs are resources lost due to inability to work and are relevant for diseases that strike in the early years before normal retirement. Indirect costs include costs of lost production due to short-term absence from work, permanent disability and death before 65 years of age. There are few studies that measure and compare both direct and indirect costs of cancer. Available studies show that indirect costs account for 70% 85% of the total costs [4]. For example, in the United States, the National Institutes of Health estimates the proportion of indirect costs out of the total cost of illness of cancer to 71% in 2000 and 65% in 2002, and in Canada, Health Canada assess the indirect costs to represent 83% of total costs, based on data from 1998 [6, 7]. Another USA study also estimated the proportion of indirect costs to 71% based on data for 1990 [8]. However, the share of direct costs as a proportion of the total cost of illness could be expected to increase over time as more treatment options become available. Indirect costs are dominated by cost of mortality in persons of working age [9]. Yet, as the survival of cancer patients improves with earlier detection and improvements in cancer treatment, the share of indirect costs due to morbidity can be expected to increase and the share due to mortality to drop. This has been seen in the United States, where the share for the cost of mortality declined from 71% to 65% between 1975 and 1985 [9]. direct costs of cancer The direct health care cost of cancer care has been estimated in some countries. However, it is not always easy to separate health care costs into various diseases and the cost of cancer is also changing over time, which may explain why various studies in some cases have reported different estimates. In Europe, data for Germany and France indicate that 6.6% and 5.3%, respectively, of total health care budgets in these two countries is spent on cancer [10, 11]. Three studies from The Netherlands estimates that cancer accounts for 4.1% (in 2004) [12], 3.2% (in 1994) [13] and 4.8% (in 1988) [14] of the total cost of national health care that can be attributable to specific diseases. Polder et al. [15] compared Organisation for Economic Co-operation and Development (OECD) data with a new calculation of cost of illness, based on country-specific studies. They report that cancer constitutes 3.9%, 4.8%, 3.9% and 4.7% of the total health expenditure in The UK, Germany, The Netherlands and Sweden, respectively. Another study from the UK estimates the proportion of health care cost spent on cancer to 10.6% in 2000/2001 [16]. It should be noted that this UK estimate is considerably higher than the UK estimate by Polder et al. and also higher than reported estimates in most other countries. A study by Bosanquet et al estimate cancer care spending in Czech republic, Hungary and Poland to 5% of total expenditures [17]. In the United States, cancer costs have consistently been reported to constitute 5% of total health care expenditure from 1963 to 1995 [16, 18]. In Canada, one study estimated that 6.7% of the health care budget is spent on cancer [6], while Polder et al. [15] estimated a proportion of 4.5%. A report from the Australian Institute of Health and Welfare estimates that cancer accounts for 6% of total health care cost in 1993 1994, while a calculation by Polder et al. estimates that cancer accounts for 5.2% in Australia [15, 19]. In Japan, cancer Volume 18 Supplement 3 April 2007 doi:10.1093/annonc/mdm097 iii9

constituted 9.3% of the nation medical care expenditures in 2002. The proportion attributable to cancer in Japan has increased over time, from 6% to 7% in the 1980s to 8% 9% in the 1990s and 2000s [20]. Table 2 presents total costs for cancer care, in purchasing power parity (PPP) adjusted 2004. The figures are based on data from OECD on total health care expenditure as well as estimates of the share for spending on cancer reported in the studies reviewed above. In cases where several estimates are available, the most recent figures have been used. Where no studies are available, it has been assumed that cancer accounts for 6.6% of total health care expenditure, which is the average proportion of the countries for which estimates could be found. As shown in Table 2, in 2004 the direct costs for cancer in the 19 European countries included in the study were estimated to be 57 billion, on average 125 per inhabitant. France, Germany, Italy, Spain and the UK combined account for twothirds of the total spending. In the United States and Japan, the total health care costs for cancer were estimated at 62 billion and 20 billion, respectively. For all countries (excluding South Africa where data were missing) included in the report, direct health care costs amounted to 146 billion. Table 3 shows the distribution of the direct costs of cancer care across different types of services for a selection of countries based on data from a variety of sources. These data show that inpatient hospital care dominates, accounting for 70% of the total health care costs of cancer. The proportion of total costs spent on ambulatory care was dependent on what was included in this category across the data sources (e.g. in France transportation of patients is a major cost calculated separately). The proportion of the cancer health care costs attributed to drug costs was reported to be lowest in France and the United States (4%) and highest in The Netherlands and Spain (11 16%). However, there are large differences in the year the estimates were published and it is plausible that the share of drug cost has increased over time. The more recent studies indicate that cancer drugs account for 10% of the total cancer cost. The estimated 4% for the United States is therefore likely not representative of the situation today. the costs of cancer drugs The cost of cancer drugs can be considered (i) in absolute terms, (ii) in relation to the total health care spending for cancer and/or (iii) in relation to the total drug spending. One of the challenges in estimating and reporting the cost of cancer drugs is that the payment of drugs varies. For example, in some cases cancer drugs are used for hospital inpatients and therefore paid for through the financing of inpatient care either per diem (based on day of hospital stay), through a global hospital budget or through a Diagnosis Related Groups system. In the last case, the budget is allocated for Table 2. Direct costs for cancer care in selected countries in 2004 (costs are PPP adjusted, total health expenditure from OECD Health Data 2006) Direct costs for cancer ( million) Direct costs for cancer per capita ( ) Cancer costs as % of total health care costs Total health care expenditure ( million) Population (2004) Austria 1247 153 6.6 18 897 8 175 000 Belgium 1543 148 6.6 23 375 10 399 000 Czech Republic 514 50 5.0 [17] 10 287 10 211 000 Denmark 760 141 6.6 11 516 5 401 000 Finland 571 109 6.6 8648 5 228 000 France 7458 124 5.3 [11] 140 714 60 200 000 Germany 12 108 147 6.6 [10] 183 455 82 491 000 Greece 1168 106 6.6 17 698 11 060 000 Hungary 495 49 5.0 [17] 9897 10 107 000 Ireland 513 127 6.6 7769 4 044 000 Italy 6725 117 6.6 101 888 57 553 000 Netherlands 1502 92 4.1 [12] 36 643 16 275 000 Norway 890 194 6.6 13 478 4 592 000 Poland 1138 30 5.0 [17] 22 758 38 180 000 Portugal 930 89 6.6 14 098 10 509 000 Spain 4367 102 6.6 66 169 42 692 000 Sweden 1316 146 7.0 [9, 21, 22] 18 802 8 994 000 Switzerland 1471 199 6.6 22 294 7 391 000 UK 5634 94 5.0 112 719 59 778 000 Europe 56 664 125 6.4 841 105 453 280 000 United States 62 321 212 4.7 [18] 1 325 988 293 655 000 Canada 5013 157 6.7 [6] 74 818 31 946 000 Japan 19 750 155 9.3 [20] 212 370 127 687 000 Australia 2199 109 5.2 [15] 42 298 20 111 000 New Zealand 413 102 6.6 6261 4 061 000 South Africa ND ND ND 12 586 42 769 000 PPP, purchasing power parity; OECD, Organisation for Economic Co-operation and Development; ND, no data. iii10 Volume 18 Supplement 3 April 2007

hospitalisation costs based on a classification of patients in different disease categories. In other cases, drugs are used in hospital outpatient departments and reimbursed separately. Additionally, cancer drugs such as antiemetics drugs (used to combat the nausea and sickness that can be brought on by cancer treatment) are prescribed by the physicians, delivered through the pharmacy and paid for through the national reimbursement system for prescription drugs. In this case, costs could be reported with or without costs for distribution by wholesalers and pharmacies. In some cases, taxes may also be added. Table 4 indicates the costs for cancer drugs in the different countries in 2004. It is important to acknowledge, however, that reliable data are difficult to obtain. We present two Table 3. Cancer health care costs as a proportion of total costs and distribution of direct costs of cancer on inpatient care, ambulatory care and drugs [6, 8, 12, 14, 15, 21 25] Inpatient care Ambulatory care Drugs Germany (2002) 67% + 9% other 16% 8% Sweden (2002) 75% (hospital) 15% (including home care) 10% France (1998) 83% 7% + 6% transport costs 4% The Netherlands (1994) 60% + 11% nonhospital institutional care 18% 11% Canada (1998) 75% 17% (physician care + additional direct costs) 9% United States (1990) 65% 31% 4% Australia (1993/1994) 71% (including nursing home) 26% 3% Spain (1998, one region) 77% 7% 16% Table 4. Cost for cancer drugs in different countries 2004 (costs are PPP adjusted, total drug expenditure for Belgium, Portugal, UK and New Zealand are calculated based on estimates of the percentage of drug expenditure to total expenditure estimates from 2000) Total drug expenditure per capita ( ) Costs for cancer drugs ( million) Costs for cancer drugs per capita ( ) Costs for cancer drugs ( million) Costs for cancer drugs per capita ( ) Based on an assumed proportion of total drug cost (5%) Based on the sale of 67 cancer drugs Austria 301 123 15 161 20 13 Belgium 255 133 13 198 19 13 Czech Republic 222 113 11 135 13 26 Denmark 200 54 10 62 11 8 Finland 270 71 14 81 15 14 France 442 1330 22 1364 22 18 Germany 325 1340 16 1291 16 11 Greece 278 154 14 Hungary 270 136 14 186 18 38 Ireland 238 48 12 Italy 379 1091 19 1004 17 15 The Netherlands 259 211 13 190 12 13 Norway 279 64 14 42 9 5 Poland 176 336 9 247 6 22 Portugal 311 163 16 Spain 353 754 18 716 16 16 Sweden 257 116 13 125 14 9 Switzerland 314 116 16 107 14 7 UK 298 891 15 638 11 5 Europe 320 7252 16 6670 15 12 United States 751 11 027 38 9244 31 15 Canada 560 894 28 410 13 8 Japan 425 2713 21 2838 22 14 Australia 408 410 20 246 12 11 New Zealand 300 61 15 26 6 6 South Africa ND ND ND 87 2 PPP, purchasing power parity; ND, no data. Cancer drugs cost as proportion of total direct cancer costs Volume 18 Supplement 3 April 2007 doi:10.1093/annonc/mdm097 iii11

estimates of the drug costs. The first numbers presented are estimates based on an assumption regarding the share of drug costs spent on cancer drugs. We have estimated that cancer drugs account for 5% of the costs of all drugs, in line with how drug costs are usually reported in the OECD health statistics. The second number presented is the total sale of 67 cancer drugs in 2004. These drugs are likely to constitute the majority of cancer drugs used in 2004 and may therefore be a fairly valid estimate of the total cancer costs. The data are from IMS and it should be noted that estimates for a few of the countries may be incomplete due to a lack of data. The sale is PPP adjusted to be comparable with the first estimate based on OECD data. There are also other estimates reported in the literature which may give other percentages but there are a number of explanations why different estimates for the cost of cancer drugs can be found from different sources. Higher estimates may be due to (i) the definition of oncology drugsõ, (ii) inclusion of sales of some oncology drugs for other indications (such as rheumatoid arthritis and hepatitis) and (iii) the price level in which drug costs are reported (including or excluding distribution costs for wholesales and pharmacies). It may also depend on which definition of drug costs that is used (hospital/prescription/over the counter) and if taxes are included or not. Based on an assumed proportion of total drug expenditure, the total cancer drug cost per inhabitant in the EU countries is estimated at 16, which amounts to 13% of total per capita health care expenditure for cancer. The total cost of cancer drugs in Europe would then be 7.3 billion. In the United States, the corresponding cost would be 11 billion. Comparing these estimates with the sale of the 67 cancer drugs show slightly different results, the sale of these drugs constitute on average 4.2% of the total drug cost, ranging from 2.0% to 7.5%. As can be noted using both estimates of cancer drug cost, the per capita cost is considerably higher in the United States than in the other countries. Comparing the sale of 67 cancer drugs with the total direct health care cost for cancer, indicates that drug costs constitute on average 12% of total direct cancer costs. The proportion was estimated at between 5% and 9% in Norway, UK, New Zealand, Switzerland, Denmark and Canada, between 9% and 14% in Sweden, Germany, Australia, Belgium, The Netherlands, Austria and Finland, between 14% and 20% in Japan, Italy, United States, Spain and France and >20% in Czech Republic, Hungary and Poland. indirect costs of cancer Detailed information about the indirect cost for cancer is scarce. Indirect cost may be divided into cost of mortality and cost of morbidity (sick leave and early retirement). The indirect cost of individual cancer types depends on the age distribution of the patients, since patients above retirement age do not incur cost of production loss. Data from Germany [10] show that, in 2002, 431 000 working life-years were lost due to cancer in the working population, representing 8% of the all life-years lost in the general German population. There are great differences in the distribution of the indirect costs between different types of cancer, with breast and lung cancer being the most important in terms of working years lost in Germany. These two cancer types are followed by leukaemia, which often occurs in children and therefore leads to many working years lost, while prostate cancer, which mainly occurs in elderly men, is not as important in terms of lost working years. Multiplying the gross average 2002 German wage of 34 000 (including social insurance contributions) by the number of the working years lost, the total amount lost is 14.7 billion. This is 20% 25% more than the total direct cost for cancer in Germany. However, costs due to morbidity should be added to this total to gain a better understanding of the indirect costs of cancer. The National Institute of Health in the USA estimated the total indirect cost of cancer in 2002 to $171.7 billion, $60.9 billion (35%) of which is direct costs, $15.5 (9%) indirect cost of morbidity and $95.2 (55%) indirect mortality cost [26]. Another USA study, from 1990, estimates the direct, morbidity and mortality costs at $27 billion (29%), $10 billion (10%) and $59 billion (61%), respectively [8]. A third US study compared medical cost and cost of morbidity in patients diagnosed with seven types of cancer in 1999 2000 with matched controls. The monthly incremental direct cost was estimated at $3600 and the morbidity costs at $1000 (i.e. 25% of the direct cost, which is close to the estimate by the National Institutes of Health in 2002) [27]. Data from Sweden, presented in Table 5, show that the indirect cost for cancer constitutes 50% of the total cost, and that the majority of the indirect cost is due to cost of mortality (78% of the indirect cost) [28]. The estimated costs in Table 5 are slightly higher than previous estimates for Sweden presented above, which partly may be explained by different definition of the resources included in cost calculation. The figures in Table 5 are also not PPP adjusted. Similar data from the other countries included in this study are not available. However, it is important to ensure the Table 5. Direct and indirect cost of cancer year 2000 and 2004 in Sweden [28] (in million ) 2000 2004 Direct costs Health care costs 1153 1572 Drug cost 112 218 Secondary prevention 16 22 Sum direct cost 1281 1812 Indirect costs Mortality 1334 1412 Sick leave 168 178 Early retirement 197 209 Sum indirect cost 1699 1799 Sum total cost 2981 3611 iii12 Volume 18 Supplement 3 April 2007

Figure 1. (A) Female incidence of cancer in selected countries (Canada, Czech Republic, Denmark, Finland, New Zealand, Norway and Sweden) given as age-standardised rate per 100 000 inhabitants. (B) Male incidence of cancer in selected countries (Canada, Czech Republic, Denmark, Finland, New Zealand and Sweden) given as age-standardised rate per 100 000 inhabitants. indirect costs are not forgotten when considering the overall picture of the costs of cancer to society. Despite the fact that most cancers occur in older persons, indirect costs of cancer are still greater than the direct costs and constitute a major part of total costs for all diseases. conclusions This section of the report highlights cancer as a common and major health care issue in terms of mortality, morbidity and indirect and direct costs, yet the share of health care expenditure allocated to cancer (4% 7%) is significantly Volume 18 Supplement 3 April 2007 doi:10.1093/annonc/mdm097 iii13

Figure 2. (A) Female mortality of cancer in Australia, Austria, Belgium, Canada, Czech Republic, Denmark, Finland and France, given as age-standardised rate per 100 000. (B) Male mortality of cancer in Australia, Austria, Belgium, Canada, Czech Republic, Denmark, Finland and France, given as agestandardised rate per 100 000 inhabitants. There are remarkable differences between, for example, Finland which has the lowest rate (125/100 000) and Czech Republic which has the highest rate (200/100 000). lower than the share of the burden of the disease (accounting for 17% of all DALYs in EU 25 and 13% in the United States and Canada). Indirect costs constitute the majority of the total cost of cancer, although the available data indicate that the direct health care cost cancer constitutes a growing share of the total costs. Health care costs for cancer are dominated by costs for inpatient care, with drug costs accounting for 10% 15% of total health care expenditure for cancer. Of concern is that the introduction of new innovative cancer drugs will result in an increase in the costs of cancer iii14 Volume 18 Supplement 3 April 2007

Figure 3. (A) Female mortality of cancer in Germany, Greece, Hungary, Ireland, Italy, Japan, The Netherlands and New Zealand, given as age-standardised rate per 100 000 inhabitants. Greece and Japan have the lowest mortality while Hungary by far has the highest mortality. (B) Male mortality of cancer in Germany, Greece, Hungary, Ireland, Italy, Japan, The Netherlands and New Zealand, given as age-standardised rate per 100 000 inhabitants. Hungary has by far the highest mortality. drugs, both in absolute terms and as a share of total health care costs. disclosures Drs Jönsson and Wilking have reported that the publication of this supplement was sponsored by an unrestricted educational grant from Roche Pharmaceuticals. references 1. Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol 2006; 24(14): 2137 2150. 2. Boyle P, Ferlay J. Cancer incidence and mortality in Europe, 2004. Ann Oncol 2005; 16(3): 481 488. Volume 18 Supplement 3 April 2007 doi:10.1093/annonc/mdm097 iii15

Figure 4. (A) Female mortality of cancer in Norway, Poland, Portugal, Spain, Sweden, Switzerland, UK and the USA, given as age-standardised rate per 100 000 inhabitants. (B) Male mortality of cancer in Norway, Poland, Spain, Sweden, Switzerland, UK and the USA, given as age-standardised rate per 100 000 inhabitants. Sweden and Switzerland have the lowest mortality, while Poland has the highest. 3. International Agency for Research on Cancer. CANCERMondial. 2005 http:// www-dep.iarc.fr/. 4. World Health Organization. Priority medicines for Europe and the world. WHO/EDM/PAR/2004.7.2004; http://whqlibdoc.who.int/hq/2004/ WHO_EDM_PAR_2004.7.pdf. 5. WHO Death and DALY estimates for 2002 by cause for WHO Member States. http://www.who.int/healthinfo/statistics/bodgbddeathdalyestimates.xls. 6. Economic Burden of Illness in Canada, 1998. Health Canada 2002; www.phac-aspc.gc.ca/publicat/ebic-femc98/pdf/ebic1998.pdf. 7. Disease-specific Estimates of Direct and Indirect Costs of Illness and NIH Support. National Institutes of Health 2000. 8. Brown M, Lipscomb J, Snyder C. The burden of illness of cancer: economic cost and quality of life. Annu Rev Public Health 2001; 22: 91 113. iii16 Volume 18 Supplement 3 April 2007

Figure 5. Female incidence of breast cancer in selected countries (Canada, Czech Republic, Denmark, Finland, New Zealand, Norway and Sweden), given as age-standardised rate per 100 000 inhabitants. The incidence has gone up by a factor of two to three over the last 50 years. Figure 6. Female mortality of breast cancer in Australia, Austria, Belgium, Canada, Czech Republic, Denmark, Finland and France, given as agestandardised rate per 100 000 inhabitants. Belgium and Denmark have a higher rate (25/100 000) compared with the rest (15 20/100 000). 9. Jönsson B, Karlsson G. Economic evaluation of cancer treatments. In Domello of L (ed): Drug Delivery in Cancer Treatment III. Berlin-Heidelberg, Germany: Springer-Verlag 1990. 10. Gesundheit Krankheitskosten 2002. Wiesbaden, Germany: Statistisches Bundesamt 2004. 11. Santé-Solidarités. Publications de la DREES. 2002 http://www.sante.gouv.fr/ htm/publication/. 12. National Institute for Public Health and the Environment (RIVM). Cost of illness in the Netherlands. 2004; http://www.rivm.nl/kostenvanziekten/site_en/ index.htm. Volume 18 Supplement 3 April 2007 doi:10.1093/annonc/mdm097 iii17

Figure 7. Female mortality of breast cancer in Germany, Greece, Hungary, Ireland, Italy, Japan, The Netherlands and New Zealand, given as agestandardised rate per 100 000 inhabitants. Japan has the lowest mortality (8/100 000). The other countries vary between 15 20/100 000. Figure 8. Female mortality of breast cancer in Norway, Poland, Portugal, Spain, Sweden, Switzerland, UK and the USA, given as age-standardised rate per 100 000 inhabitants. UK has, in spite of a sharp decline over the last two decades, the highest mortality (20/100 000). The other countries have a similar mortality rate (15/100 000). 13. Meerding WJ et al. Demographic and epidemiological determinants of healthcare costs in Netherlands: cost of illness study. BMJ 1998; 317(7151): 111 115. 14. Koopmanschap MA et al. Current and future costs of cancer. Eur J Cancer 1994; 30A(1): 60 65. 15. Polder JJ et al. A cross-national perspective on cost of illness: a comparison of studies from The Netherlands, Australia, Canada, Germany, United Kingdom, Sweden. Eur J Health Econ 2005; 6(3): 223 232. 16. Bosanquet N, Sikora K. The economics of cancer care in the UK. Lancet Oncol 2004; 5(9): 568 574. iii18 Volume 18 Supplement 3 April 2007

Figure 9. (A) Female incidence of lung cancer in selected countries (Canada, Czech Republic, Denmark, Finland, New Zealand, Norway and Sweden), given as age-standardised rate per 100 000 inhabitants. Canada and Denmark have the highest incidence (30/100 000) and Finland the lowest (10/100 000). (B) Male incidence of lung cancer in selected countries (Canada, Czech Republic, Denmark, Finland, New Zealand, Norway and Sweden), given as age-standardised rate per 100 000 inhabitants. Canada, Czech Republic and Denmark have the highest incidence (50 70/100 000) and Sweden the lowest (20/100 000). 17. Bosanquet N, Attridge J, Sikora K. Can the new EU members catch up in cancer care? EuroHealth 2005; 11(1). 18. Cancer Trends Progress Report 2005 Update. Bethesda, MD: National Cancer Institute, NIH, DHHS 2005. 19. Mathers C et al. Health system costs of cancer in Australia 1993 94. Canberra, Australia: The Australian Institute of Health and Welfare and the National Cancer Control Initiative of the Commonwealth Department of Health and Family Services 1998. 20. Cancer Statistics in Japan 05, National medical care expenditure trends in Japan. (1977 2002) www.ncc.go.jp/en/statistics/2005/ index.html. Volume 18 Supplement 3 April 2007 doi:10.1093/annonc/mdm097 iii19

Figure 10. (A) Female mortality of lung cancer in Australia, Austria, Belgium, Canada, Czech Republic, Denmark, Finland and France, given as agestandardised rate per 100 000 inhabitants. Canada and Denmark have the highest mortality (30/100 000) while Finland and France have the lowest (10/100 000). (B) Male mortality of lung cancer in Australia, Austria, Belgium, Canada, Czech Republic, Denmark, Finland and France, given as age-standardised rate per 100 000 inhabitants. Belgium and Czech Republic have the highest mortality (60/100 000) while Australia and Finland have the lowest (30/100 000). 21. Center for Medical Technology Assessment. Cost of illness in the county of Östergötland in 2002. CMT report. 22. Ragnarson Tennvall G, Karlsson G. Cancer treatment in Sweden costs of drugs, inpatient and outpatient care from 1985 to 1996 and cost effectiveness of new drugs. Acta Oncol 1998; 37(5): 447 453. 23. Organisation for Economic Co-operation and Development. OECD Health Data 2005: Statistics and Indicators for 30 Countries. 2005; http://www.oecd.org/ document/3002340,en_2469_201185_12968734_1_1_1_1,00.html. 24. Swedish Council on Technology Assessment in Health Care. SBU Yellow Report. Chemotherapy for cancer. Report no. 155/2. 2001; http://www.sbu.se/www/index.asp. iii20 Volume 18 Supplement 3 April 2007

Figure 11. (A) Female mortality of lung cancer in Germany, Greece, Hungary, Ireland, Italy, Japan, The Netherlands and New Zealand given as agestandardised rate per 100 000 inhabitants. Greece, Italy and Japan have the lowest mortality (10/100 000). (B) Male mortality of lung cancer in Germany, Greece, Hungary, Ireland, Italy, Japan, The Netherlands and New Zealand given as age-standardised rate per 100 000 inhabitants. Japan has the lowest mortality (30/100 000) while Hungary has the highest (80/100 000). 25. Lopez-Bastida J, SerranoAguilar P, Duque-Gonzalez B. Los costes socieeconomicos de las enfermedades cardiovasculares y del cancer en las Islas Canarias en 1998. Gac Sanit 2003; 17(3): 210 217. 26. Cancer facts and figures. American Cancer Society 2003. 27. Chang S et al. Estimating the cost of cancer: results on the basis of claims data analyses for cancer patients diagnosed with seven types of cancer during 1999 to 2000. J Clin Oncol 2004; 22(17): 3524 3530. 28. Cancerfondsraporten 2006. Swedish Cancer Society. www.cancerfonden.se. Volume 18 Supplement 3 April 2007 doi:10.1093/annonc/mdm097 iii21

Figure 12. (A) Female mortality of lung cancer in Norway, Poland, Portugal, Spain, Sweden, Switzerland, UK and the USA given as age-standardised rate per 100 000 inhabitants. UK and the USA have the higest mortality (20 30/100 000) while Portugal and Spain have the lowest (5/100 000) mortality. (B) Male mortality of lung cancer in Norway, Poland, Portugal, Spain, Sweden, Switzerland, UK and the USA given as age-standardised rate per 100 000 inhabitants. Poland has the higest mortality (70/100 000) while Sweden has the lowest (20/100 000) mortality. iii22 Volume 18 Supplement 3 April 2007