Original article. Prevention of colorectal cancer: A cost-effectiveness approach to a screening model employing sigmoidoscopy. J.

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1 Annals of Oncology 9: Kluwer Academic Publishers. Primed in the Netherlands Original article Prevention of colorectal cancer: A cost-effectiveness approach to a screening model employing sigmoidoscopy J. Norum Department of Oncology, University Hospital of Tromso, Tromso, Norway Summary Background: Today, only carcinoma of the bronchus kills more people than colorectal cancer (CRC). However, CRC is both preventable and curable. In Norway, projects aiming to detect adenomas and early cancers by the screening of a population aged about 60 years employing sigmoidoscopy have been discussed. Materials and methods: In this study, a mathematical model was used to estimate the cost-effectiveness of a screening programme for colorectal polyps followed by polypectomy. A once-only sigmoidoscopy at age 60 followed by coloscopy in selected risk groups was suggested. Data from the Englishlanguage literature, the National Cancer Registry of Norway, and Statistics Norway were included. Norwegian cost data from the National Health Administration were also used. Costs of screening and those related to earlier diagnosis, and savings on health care and averted loss in production due to prevented CRCs were calculated. Results: The basic cost per patient invited and screened (70% compliance) in the suggested programme was estimated at 81.7 and 116.7, respectively. When gains due to prevented CRCs were included, thefiguresbecame 34.5 and The cost per life-year saved was calculated as 2,889. This strongly indicates that screening for the early detection and prevention of CRC is one of the most cost-effective programmes in cancer. Conclusions: CRC screening according to the suggested programme appears to be cost-effective. Clear evidence that screening can reduce mortality from CRC should convince health-care policy makers that the time has come to encourage screening for colorectal cancer. Key words: colorectal cancer, screening, health economy, cost-effectiveness Introduction Except for carcinoma of the bronchus, colorectal cancer (CRC) kills more people than any other malignancy in the Western world [1]. Currently, Norway has the highest incidence of rectal cancer in the Nordic countries. According to the Cancer Registry of Norway, about 3,000 cases (2,000 of colon cancer and 1,000 of rectal cancer) and more than 1,500 deaths from CRC are reported every year [2]. The spread of the disease at presentation determines the prognosis. The five-year survival figures vary from 80%-90% to less than 5%, depending on Dukes' stage (A-D) [3]. The majority (60%) of patients still present with lymph node (Dukes' C) or distant metastases (Dukes' D). The prognosis in this malignancy (50% five-year survival) has remained virtually unchanged for more than two decades. However, during the last decade a steadily increasing number of investigators world-wide have focused on colorectal cancer prevention by endoscopic screening. There is now significant evidence that endoscopic polypectomy is a very effective means of preventing this malignancy and probably the most promising potential method for improving prognosis by detection of asymptomatic early-stage disease [4]. The great majority of colorectal tumours are asymptomatic at diagnosis and most cancers develop from adenomatous polyps [5]. Recently, a consortium consisting of the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, the American College of Gastroenterology, the Society of American Gastroenterology and Surgeons and the American Society for Colorectal Surgeons developed new guidelines for colorectal cancer screening based on recent data [6]. The 16- member multi-diciplinary panel examined the data from 350 papers selected from a pool of 3,500 papers reported in the literature on colorectal cancer screening, biology and natural history. The panel concluded that the evidence for colorectal screening effectiveness was strong and that screening for colorectal cancer and adenomatous polyps should be offered to all men and women without risk factors, beginning at age 50. Colorectal cancer is both preventable and curable, but national screening has not yet been instituted in either the United States or Norway [7]. It is likely, however, that government-sponsored colorectal cancer screening will be a reality within the next several years. In Norway, a screening project for detection of adenomas and early cancers by the screening of a certain population has been suggested [5]. This may lead to both

2 614 Table 1. The table shows a model for colorectal cancer prevention employing sigmoidoscopy and faecal occult blood test. All citizens aged 60 are offered screening Screening method Sigmoidoscopy Faecal occult blood test (FOBT) Indication for colonoscopy Adenoma < 10 mm revealed Polyp 2= 10 mm Risk of hereditary non-polyposis CRC (HNPCC) 1 10% are referred to regional departments of genetics Suggested compliance 70% Sigmoidoscopy is performed in 70% i Number of adenomas revealed by sigmoidoscopy (20%) a reduction in mortality from CRC and a decrease in its incidence. However, the incidence of CRC and the cost of screening suggest that the financial burden on health care systems will be significant. The resources spent on this intervention may have been applied in the other health care programmes which might alternatively have been performed. If the national health care authorities aim to provide as much health benefit as possible with available resources, it is crucial that both the health effects and the treatment costs be calculated. This economic study is undertaken to indicate the cost-effectiveness of a national screening programme. Materials and methods Study design In Norway, the Norwegian Gastrointestinal Cancer Group (NGICG) has issued a call for applications to develop a protocol for colorectal cancer screening based on recent data [5]. The preparation of a screening programme has been supported by the Cancer Registry of Norway and the Norwegian Cancer Association. In this study, a rationale for a national screening strategy and the cost estimates for offering Norwegians screening for CRC and colorectal polyps is presented. The screening model is summarised in Table 1. The model is based on a once-only screening of Norwegians aged 60 years employing flexible sigmoidoscopy and faecal occult blood test (FOBT). Sigmoidoscopy is recommended on the basis of experience in the Telemark Polyp Study(TPS-l)[8]. Efficacy of screening Several factors will affect the efficacy of a screening project. Among them are the expected rates of prevalent and incident cancers, the likelihood of identifying and removing adenomatous polyps, and compliance. High compliance is considered essential for a screening programme to be successful. In Australia, particularly in country areas, community screening programmes achieved a compliance of over 80% [9]. Compliance with the faecal occult blood test (FOBT) during controlled trials has ranged from 53% to 78% [10-13]. Atkin et al. [14] calculated a compliance rate of 65% in a screening programme including sigmoidoscopy. Whereas these studies show quite satisfactory compliance rates, some gastroenterologists doubt these figures are achievable in national systematic screening programmes. In this model, I have estimated a compliance rate of 70% based on the experience from the Telemark polyp study (TPS-1) [8]. TheTPS-1 study achieved a compliance rate of 81% employing flexible sigmoidoscopy. However, several factors (public interest, publicity, etc) may influence the recruitment of patients. Therefore, variations in compliance is added in a sensitivity analysis. The publicity and public interest may also influence the study by increasing "self-testing'outside the time of screening. Recommended colonoscopy due to a 1 st degree relative with CRC (5%) Total number of colonoscopies (25%) Figure 1 The stipulated number of sigmoidoscopies and colonoscopies employing the suggested screening model. CRC prevention projects employing endoscopic screening and polypectomy will have an influence on the incidence of CRC as well as the mortality of the disease. Prevalent cancers can not be prevented, but could be detected at an early stage. Atkins and coworkers indicated a 45% reduction in colorectal cancer mortality in this setting [14]. The reported reduction in the incidence of this malignancy is significant. Screening projects have indicated a screening benefit of at least 50% in CRC [14, 15]. Evidence from the National Polyp Study in the US [15], suggests that if patients with polyps are identified and all of the polyps are removed, the subsequent risk of colon cancer is reduced by 76%- 90% over a six-year follow-up period. According to the Cancer Registry of Norway (CRN), the incidence rate of CRC among Norwegians aged years during the next five years will be 1% [2]. In this model, the figures of the CRN and the prevention rate of 50% employing flexible sigmoidoscopy, as proposed by Lieberman [10] and Geul et al. [4], were employed. Costs of screening Health care costs Cost is a prominent issue because of the central place of cost-containment in modern medical care. The direct cost of various screening tests varies enormously. The estimated percentage of colonoscopy and sigmoidoscopy is shown in Figure 1. The cost of each examination in the screening model can be calculated according to the tariff of the Norwegian Medical Association (NMA) [16] and the National Insurance Administration (NIA) [17]. The costs are shown in Table 2. However, in a national screening situation, there is the possibility of a minor reduction in these costs. Screening may bring forward costs by earlier diagnosis and treatment of a CRC that otherwise would have been revealed only several months later. The advance in months is to my knowledge not indicated in the literature In this study, twelve months was calculated. Non-health care costs Screening for CRC causes production losses. For simplicity, the usual assumption was made of taking gross income as a proxy for the value of their employment. The human capital was calculated employing the mean income of Norwegian workers (1996) of 21,373 (data from Statistics Norway). The mean annual income rose by 4% in Thus, the amount of 22,228 was used in this analysis. According to Statistics Norway, about 60%-70% of the population aged 60 years are employed. Based on this fact, it was assumed that screening causes 50% of invited persons to be absent from work an average of one third of one day. A brief absence is difficult to replace in the labour market. The real production gain was therefore assumed to equal human capital. How-

3 615 Table 2. The single cost of each examination in the suggested programme according to the tariff of the Norwegian Medical Association (NMA) and/or the National Insurance Administration (NIA) [16. 17]. Examination Visit to gastroenterologist Consultation when adenoma is revealed (20%) Sigmoidoscopy Consumption when sigmoidoscopy Colonoscopy Consumption when colonoscopy Faecal occult blood test (FOBT) Pathologist Cost ( ) a 22.5 No/ invited ,000 70,000 70,000 17,500 17,500 a b a Included in the visit tax. b Number of specimen (not patients). Cost per person screened: 8,167,000/70,000 = Cost per person invited: 1,143,200/100,000 = Total cost ( ) 861,000 77,000 4,137, ,000 1,750, ,062,000 ever, when prolonged absence from work occurs, the indirect benefits should be estimated as a fraction of the patients' income [18], Savings of screening There is a consensus that most colorectal cancers originate as adenomatous polyps and it is unusual for cancer to arise denovo [15]. The American National Polyp Study [19] indicated a 76%-90% reduction in the incidence of cancer, which justifies polypectomy to prevent colorectal cancer. In this model it was indicated that the screening programme will reduce the incidence of CRC by 50% However, transformation from benign adenoma to cancer is likely to take years, almost certainly more than five and perhaps as long as 10 years [20, 21]. According to these data, the averted cancers were assumed to occur a median of seven years following screening. The incidence rate of CRC in Norway among patients aged years is 180 CRCs per 100,000 'person-years'. Calculating a 50% reduction in CRC by screening, about 900 cases (100,000 x 180/100,000 x 0.5 x 10) per 100,000 invited can be prevented within a ten-year period. During ten years of follow-up, a 9.8% mortality rate (Statistics Norway) entails a total of 812 patients saved. The benefit of prevented CRCs can be calculated by the Diagnosis Related Groups (DRG) [22]. This was introduced in Norway in The Health Care Financing Administration (HCFA) version 12 is employed. According to the national database, the cost of surgery in colon and rectal cancer (without complications) in Norway is 7,005 (DRG 149) and 7,747 (DRG 147). Prevention of CRCs would not only save the cost of surgery, but the money spent on adjuvant chemotherapy (ACT) and follow-up as well. In Norway, patients with Dukes' C colon carcinoma are offered six months of ACT consisting of 5-rluorouracil (500 mg/m 2 ) and leukovorin (100 mg) for two consecutive days every second week. Colon cancer Dukes' stage C comprises 35% of all colon cancers and colon cancer consitutes 2/3 of all CRCs in Norway [2], According to prior experience [23], it was assumed that 63% of the patients would go through ACT. A mean body surface of 1.7 m was calculated, according to the suggestion of Zalcberg et al. [24], The cost of chemotherapy and chemotherapy administration was calculated according to the price list at the Pharmacy, University Hospital of Tromso in December 1997 and the tariff of the NMA [16] and NIA [17]. The cost of followup was calculated according to the national recommended five-year follow-up program [25]. It was calculated that one-half of the patients survive five years after diagnosis. Saved life-years due to prevented CRCs may cause production gains. However, the great majority of life-years saved will be after the age of 65. The usual retirement age in Norway is between 62 and 65 years. Thus, the gain in production will be minimal, especially when calculating a real benefit of 1% of human capital, as was shown in a previous study in Hodgkin"s disease [18]. Against that background, production gain was not included in this survey. Screening will save life-years occurring five to 10 years later, and they have to be discounted. A Danish study reported an 18% reduction in death from colorectal cancer in a comparison with control groups [26]. The US Office of Technology Assessment (OTA) calculated, in a screening model employing annual FOBT from the age of 65. approximately 23,000 cases of CRC prevented and 45,000 added years of life [27]. Khullar and associates indicate that the entire screening population would gain between one week and one month [28]. Fletcher [29] indicated that sigmoidoscopy every five years in 100,000 people entering a screening program for CRC at age 50 years and remaining in it until age 85 or death will save 8,328 life-years and prevent 967 cancer deaths. Whereas screening prevents cancer deaths, other causes (i.e., cardiovascular disease) become more important and may to some degree balance the benefit of screening. The mean life expectancy of a 60-year-old cohort of Norwegians is 21.2 years (Statistics, Norway). Upon contracting a CRC, half of the patients will survive five years Based on all these publications and the knowledge that screening will prevent cancers five to 10 years later, a reasonable and moderate estimate would be two years saved per CRC prevented. This figure was employed in this analysis Statistics The Microsoft Excel version 7.0 for personal computers was employed for the database and calculations. Costs and benefit occurring in the future have to be discounted. In this analysis, a 5% discount rate was employed according to the recommendations of Luce and Elixhauser [30]. All costs were converted to British pounds at the rate of 1 = N.O.K Results Costs In this study, the basic cost of CRC screening employing the tariff of the Norwegian Medical Association (NMA) [16] and the National Insurance Administration (NIA) [17] on a simple once-only sigmoidoscopy model at age 60 was estimated at per person screened and 81.7 per individual invited. The calculations are shown in Table 2. Sigmoidosopy constituted half of this amount. Screening may lead to an earlier diagnosis of CRC and thereby bring the costs of surgery forward. This effect was calculated as 65,271 per 100,000 invited ((120 x 7, x 7,747) x 0.05). The figure is included in Table 3. The loss in production due to the fact that people have to be absent from the work place to undergo sigmoidoscopy was estimated as 710,484 (( 22,228 x 70,000 x 0.5 x l)/3 x 365). Savings Prevention of CRCs saves money due to the fact that surgery, ACT and follow-up are not needed. Surgical interventions avoided will save 4,556,906 ((541 x 7, x 7,747) x ) in a cohort of 100,000 persons invited. The corresponding savings in ACT and followup were 201,894 ((541 x 3,688 x 0.63 x23%/100%) x ) and 734,066 ((541 x 1,943) x ), respectively. No production gain was included.

4 616 Table 3. The cost per life-year gained in an endoscopic screening model for colorectal polyps and polypectomy is shown. The figures are for a cohort of 100,000 persons invited. Costs/savings Cost of screening (per person screened; see Table 2) Cost of early diagnosis. 25 CRCs (eight rectal, 17 colon) one year forward 65,271" Cost due to loss in production (1 / 3rd day off in half of the population) 710,484 Saving due to prevented CRCs (541 colon and 271 rectal cancers) a median time of seven years following screening Prevented costs of CRC surgery 4,556, 906 a Prevented costs of adjuvant chemotherapy (six months FLv in Dukes' C) 201,894 a Averted follow-up costs 734,066" Non-health-care savings. Gain in production due to prevented CRCs 0 Life years (LY) gained occurring seven years in the future LY = 812 cases per two years = 1,624 years = 1,194 years a Cost per life-year saved; (costs - savings)/ly = (8,942,755-5,492,866)/1,194 = 2,889" Net cost per person invited; (8,942,755-5, )/100,000 = 34.5 Net cost per person screened (70% compliance); (8,942,755-5,492,866)/70,000 = 49.3 a Five percent discount rate is employed. Cost-effectiveness The net costs of CRC screening per patient screened and invited were 49.3 and 34.5, respectively. Discounting (seven years) the 1,624 life-years gained, the cost per lifeyear saved can be seen as 2,889. This strongly indicates that this project is worth its costs. Although I would argue that the current study has followed a sound methodology for cost-effectiveness analysis, the compliance (70%) and life-years (LY) saved (two years/prevented cancer) are based on prior national and international reports and contain uncertainties. To clarify limits, a sensitivity analysis was performed. When assuming a linear correlation between compliance and CRCs detected and/or prevented, the cost per life-year saved will remain almost constant. However, the number of years gained per prevented CRC is the major factor influencing cost-effectiveness. If life-years gained per prevented CRC are reduced from two to one year, the cost per year saved doubles. Using two cut-off points employed in the literature ( 12,000 and 24,000) [27, 28], between three and six months need to be gained per case of CRC prevented to render the procedure cost-effective. This benefit should be a focus of future studies. Discussion Evidence of effectiveness remains an essential in the choice among alternative screening strategies. It is difficult to attach monetary value to human life, but most health authorities use some monetary comparison. Despite limitations of cost-effective analysis, sums of less than 12,100 (USS 20,000) per added year of life are usually considered worth paying [28]. According to Khullar et al. [29], costs within the benchmark figure of USS 40,000 ( 24,100) per year of life saved is considered by the US government to be cost-effective. In this setting, the 2,889 in this model strongly indicates that screening for CRC should be encouraged. My calculations are based on several assumptions. I have tried to present the effect of CRC screening as accurately as possible on the basis of the available literature data. It could be argued that a cost-effectiveness analysis of CRC screening should be based on a randomised prospective study. However, the use of models has advantages. Different events and data obtained from a large number of studies can be structured in a logical and chronologically correct manner. On the other hand, prospective collected data may look more reliable. But, even with unlimited funding, the logistics of collecting and analysing the data necessary for meaningful comparisons of the most promising screening strategies are probably beyond the human resources that can be devoted to the problem. Thus, rather than engage in the prospective collection of vast quantities of data to determine the most cost-effective screening programme, mathematical modelling can be applied to project the cost effectiveness using available data. When interpreting the results of cost-effectiveness analysis, two problems with the perspective must be borne in mind. First, the cost of the screening project itself, apart from its effectiveness, does matter in the short term to those who must pay for it in the present. Second, in general the risk and costs of CRC screening occur long before the benefits. Each country must weigh the costs against the economic and social burden of treating patients with late-stage CRC. National screening programmes will require a commitment of resources that some nations may not choose to expend. In the United States, the Preventive Task Force has recommended screening with annual FOBTor sigmoidoscopy every five years in average-risk persons aged over 50. It is estimated that routine FOBT and sigmoidoscopic screening of the 62 million persons over the age of 50 in the United States would cost more than SI billion per year in direct charges [31]. To my knowledge, it is not known whether healthinsurance providers or the US government will prove willing to pay for screening based on this recommendation. The costs in this analysis are calculated solely from the viewpoint of the health care system and do not take into account the amount paid by patients or their families (i.e., travelling costs). However, since the Norwegian tax system includes all Norwegians as compulsory members of the NIA, only minor amounts have to be paid by the patients and their families. The high compliance rate in thetps study [8] indicates that patients and their families are prepared to bear these costs. Another extra cost may be incurred by detection and

5 617 Table 4. Medical cost per life-year saved for selected types if lifesaving interventions from Tengs et al. [32]. Intervention Colorectal screening Cholesterol screening Cervical cancer screening Antihypertensive drugs Osteoporosis screening Coronary artery bypass surgery Automobile seat belts and air bags Renal dialysis Heart transplant Median cost per life-year saved (S) 3,000 6, ,000 18, ,000 46,000 54,000 treatment of some cancers that would have remained silent throughout a person's life in the absence of the screening program. However, the number of such cases was considered low and difficult to estimate and was not included in the analysis. Had it been included, only a minor change in the cost would have been noted. In this study, the real production loss was calculated equal human capital and the human capital was based on the mean income of Norwegian workers. It could be argued that it should be estimated on a fraction of income. Due to the fact that everyone in the work force could be replaced in the labour market by the unemployed, the real production loss may be reduced. In a prior study in Hodgkin's disease, the real production gain was calculated as 10% [18]. But, whereas replacement make sense when a person remains absent from work for days or months, this is not obvious in a I /3rdday-off situation. I will therefore argue that in this situation replacement is difficult and the real production loss calculated should be raised. What cohort should be offered CRC screening? In this model, persons aged 60 were included. The elderly population is most likely to be afflicted by CRC. The incidence of the disease is relatively low in the young adult population. An important attribute of CRC is that the incidence is minimal until age 50, but rises steadily thereafter. The great majority of screening strategies include individuals aged 50 years or more. In this setting, this model seems reasonable. Including younger adults will significantly reduce cost-effectiveness. Today several screening programmes are suggested in cancer. The ones to be chosen should be decided by clinical studies evaluating health effects and treatment costs. In 1995 Tengs et al. [32] listed five-hundred lifesaving interventions. Some of them are listed in Table 4. Their study strongly indicates that screening programmes in CRC ought not to be displaced by breast cancer screening programmes. Several other reports have supported this view by demonstrating that most of the commonly suggested strategies for CRC screening are more cost-effective than breast cancer screening with mammography in women over 50 years of age [7, 33-35]. Based on these studies, national breast cancer screening programmes should not be given higher priority than colorectal cancer prevention projects employing endoscopic screening with polypectomy. Analyses have shown that the cost per added life-year in CRC screening does not even exceed the cost of other well-accepted treatments for mild hypertension, coronary artery bypass graft or chronic renal failure [28, 36]. At present, we are waiting for health-care policy makers to decide whether or not they believe the clear evidence that screening can reduce mortality from the second leading cancer killer in Europe and North America. When a cancer prevention program has been shown to make patients live longer or feel better, its use can be justified. While waiting, thousands of patients will need care for CRC every year. This suffering could be prevented in many patients with today's knowledge. In the absence of national recommendations for screening, significant amounts are used in 'wild-screening' programmes based on single patients and doctors' opinions. These resources should be allocated to standard programmes based on medical evidence, making it possible to achieve maximum value for money. As argued by Liebermann and Sleisenger [37], the time has come to encourage screening for colorectal cancer. Acknowledgements The author wish to thank Erik Nymoen at Statistics Norway for providing national statistical data on mortality and cost. I also want to thank Dr. Geir Hoffat the Department of Medicine, Telemark Central Hospital, Skien, Norway and the colleagues at the Department of Oncology, University Hospital of Tromse for their useful suggestions and comments. References 1. Hardcastle JD, Robinson MHE. Screening of colorectal cancer. Eur J Cancer 1992; 28A: Cancer in Norway The Cancer Registry of Norway, Institute for Epidemiological Cancer Research, Oslo Tveit KM, Dahl O, GernerT. Chemotherapy in colorectal cancer. J Nor Med Assoc 1996; 116: Geul KW, Bosman FT, van Blankenstein M et al. Prevention of colorectal cancer. Costs and effectiveness of sigmoidoscopy. Scand J Gastroenterol 1997; 32 (Suppl 223): Hoff G. Solheim K. Screening for colorectal cancer? J Nor Med Assoc 1997; 117: Winawer SJ, Fletcher RH, Muller L et al. Colorectal screening. Clinical guidelines and rationale. Gastroenterology 1997; 112: Gelfand Dw. Colorectal cancer. Screening strategies. Radiol Clin North Am 1997; 35: HofTG, Sauar J, Vatn MH et al. Polypectomy of adenomas in the prevention of colorectal cancer. 10 years' follow-up of the Telemark Polyp Study I. Scand J Gastroenterol 1996; 31: Bolin TD, Munday A, Brand NE A community based screening program for colorectal neoplasia Gastroenterology 1989; 96: A Lieberman DA. Cost-effectiveness model for colon cancer screening. Gastroenterology 1995: 109: Mandel JS, Bond JH, Church TR et al. Reducing mortality from

6 618 colorectal cancer by screening for fecalt occult blood. N Engl J Med 1993; 328: Winawer SJ, Schottenfeld D, Flehinger BJ Colorectal cancer screening. J Natl Cancer Inst 1991; 83: Kewenter J, Brevinge H, Engaras B et al. Results of screening, rescreening and follow-up in a prospective randomized study for detection of colorectal cancer by faecal occult blood testing. Results for subjects. Scand J Gastroenterol 1994; 29: Atkin WS, Cuzick J, Northover JMA. Whynes DK. Prevention of colorectal cancer by once-only flexible sigmoidoscopy. Lancet 1993; 341: Winawer SJ, Zauber AG, Ho MN et al. Prevention of colorectal cancer by colonoscopic polypectomy. N Engl J Med 1993; 329: The tariff for medical specialists Oslo: The Norwegian Medical Association The tariff of public out-patient treatment valid from July 1 st. Oslo: The National Insurance Administration Norum J, Angelsen V, Wist E, Olsen JA. Treatment costs in Hodgkin's disease. A cost-utility analysis. Eur J Cancer 1996; 32A: Bolin TD. Cost benefit of early diagnosis of colorectal cancer. Scand J Gastroenterol Suppl 1996; 220: Slryker SJ, Wolff BG, Culp CE et al. Natural history of untreated colonic polyps. Gastroenterology 1987; 93: Rex DK, Lehman GA, Utbrigt TM et al. The yield of a second screening flexible sigmoidoscopy in average risk persons after one negative examination. Gastroenterology 1994; 106: The National Institute of Health. DRG price list 1997 and codes. HCFA-12. Oslo: The National Institute of Health Norum J, Vonen B, Olsen JA, Revhaug A. Adjuvant chemotherapy (5-fluorouracil and levamisole) in Dukes' B and C colorectal carcinoma. A cost-effectiveness analysis. Ann Oncol 1997; 8: Zalcberg JR, Siderov J, Simes J. The role of 5-fluorouracil dose in the adjuvant therapy of colorectal cancer. Ann Oncol 1996; Norum J. A cost-effectiveness approach to the Norwegian followup programme in colorectal cancer. Ann Oncol 1997; 8: Kronborg O, Fenger C. Olsen J. Interim report on a randomised trial of screening for colorectal cancer with Haemoccult-II. In Miller AB, Chamberlain J (eds): Cancer Screening. Cambridge: Cambridge University Press 1991; Office of Technology Assessment, US Congress. Cost and Effectiveness of colorectal cancer screening in the elderly. Background paper. Washington DC: US Government Printing Office Fletcher RH. Screening for colorectal cancer. Weighing the alternatives. In Perry MC, Whippen D (eds): American Society of Clinical Oncology Educational Book. 33rd Annual Meeting. Alexandria, VA: American Society of Clinical Oncology 1997; Khullar SK, DiSario JA. Colon cancer screening. Sigmoidoscopy or colonoscopy. Gastrointest Endosc Clin N Am 1997; 7: Luce BR, Elixhasuer A. Standards for the Socioeconomic Evaluation of Health Care Services. Berlin: Springer-Verlag dayman CB. Mass screening for colorectal cancer. Are we ready? JAMA 1989; Tengs TO, Adams M, Pliskin J et al. Five hundred life-saving interventions and their cost-effectiveness. Risk Anal 1995; 15' Brown ML. Screening for colorectal cancer. N Engl J Med 1993; 329: Atkin WS, Cuzick J, Northover JMA, Whynes DK. Prevention of colorectal cancer by once-only sigmoidoscopy. Lancet 1993; 341: Ransohoff DF, Lang CA. Cost-effectiveness of one-time colonoscopy screening to reduce colorectal cancer mortality. Gastroenterology 1994; 106 (Suppl): A24 (Abstr) 36. Wagner JL, Tunis S, Brown M et al. Cost-effectiveness of colorectal cancer screening in average-risk adults. In Young GP, Rozen A, Levin B (eds): Prevention and Early Detection of Colorectal Cancer. London: WB Saunders 1996; Lieberman D, Sleisenger MH. Is it time to recommend screening for colorectal cancer? Lancet 1996, 348: Received 5 January 1998; accepted 10 March Correspondence to: J. Norum, MD Department of Oncology P.O. Box 13 University Hospital of Tromso 9038 Tromso Norway ' jnnor(a}online.no

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