Cost-effectiveness Model for Colon Cancer Screening

Transcription

1 GASTROENTEROLOGY 1995;109: Cost-effectiveness Model for Colon Cancer Screening DAVID A. LIEBERMAN Division of Gastroenterology, Department of Medicine, Oregon Health Sciences University, and Portland Veterans Affairs Medical Center, Portland, Oregon Background & Aims: The relative efficacy and effectiveness of different colon screening programs has not been assessed. The purpose of this analysis was to provide a model for comparing several colon screening programs and to determine the key variables that impact program effectiveness. Methods: Five screening programs were compared: annual fecal occult blood test (FOBT) alone, flexible sigmoidoscopy, flexible sigmoidoscopy and FOBT combined, one-time colonoscopy, and air-contrast barium enema. Key variables were adjusted for sensitivity analyses. Cost-effectiveness was defined as the cost per cancer death prevented. Results: FOBT alone prevents fewer cancer deaths than the other programs. The addition of flexible sigmoidoscopy to the FOBT increases the rate of cancer prevention. One-time colonoscopy has the greatest impact on colorectal cancer mortality, largely because of assumptions that cancer would be prevented in most patients who undergo polypectomy. FOBT alone is the most cost-effective of the programs, but the cost is sensitive to several key variables. Conclusions: The model shows key variables that impact the cost-effectiveness of colon screening programs, Compliance is an important determinant of effectiveness of all of the screening programs. Future study should be focused on methods of patient education that improve patient compliance with screening. S everal studies have shown that screening asymptomatic populations for colon neoplasia can reduce colon cancer mortality) -3 No prior study has attempted to compare the effectiveness of different screening tests. To do so would be costly, and large numbers of subjects would be required. Nevertheless, if colon screening is to be advocated for the general population, we need to know which method of screening is most effective in clinical practice. Previous studies have estimated the costs of colon screening programs, 4-9 although some have failed to account for the complexity of a colon screening program. Colon screening is really a complex series of decisions that only begin with the screening test. When a test result is negative, subsequent retesting is generally recommended at some interval. When a test result is positive, further evaluation of the colon is usually pursued. Once neoplasia is identified, surveillance is generally performed for several years. Program effectiveness must account for each of these steps and likely patient compliance. These "downstream" costs are part of a screening program and must be incorporated into any cost analysis. Screening program costs also include the cost of cancer care and complications resulting from screening tests or evaluation of positive screening test results. Using available data, a cost-effectiveness model was developed to estimate and compare the efficacy and effectiveness of different screening programs. Five colon screening programs were evaluated in the model, based on recent literature suggesting effectiveness. Selby et al. 2 and Newcomb et al. 3 used a case-control study design to show that screening with sigmoidoscopy was associated with a reduction in fatal cancers. The benefit was limited to the region of the colon examined using sigmoidoscopy. Mandel et al) found that annual fecal occult blood tests (FOBTs) could reduce mortality by 33% over the 13-year period of observation compared with no screening. FOBT is being evaluated in several randomized control studies in Europe, which are near completion. At least one of these studies is likely to show a reduction in colon cancer mortality (O. Kronborg, personal communication, June 1994). The American Cancer Society has long recommended screening of asymptomatic individuals older than 50 years of age with both FOBT and sigmoidoscopy) Only one study has attempted to evaluate this combination of screening tests.la In this study, follow-up was irregular and compliance poor. Nevertheless, patients screened with both FOBT and sigmoidoscopy had better long-term survival after detection of cancer than controls) 1 Several investigators have suggested that screening with colonoscopy one time during the sixth decade may Abbreviations used in this paper: FOBT, fecal occult blood test; FS, flexible sigmoidoscopy by the American Gastroenterological Association /95/$3.00

2 1782 DAVID A. LIEBERMAN GASTROENTEROLOGY Vol. 109, No. 6 be more effective than the FOBT or sigmoidoscopy, s J2 Evidence from the National Polyp Study suggests that if patients with polyps are identified and if all polyps are removed at colonoscopy, the subsequent risk of colon cancer is reduced by 76%-90% over a 6-year followup. 13 Finally, Eddy 6 has suggested that screening with barium enema may be a cost-effective approach to population screening compared with the American Cancer Society recommendations. The primary goal of the present analysis was to provide a simple model for comparing the efficacy and effectiveness of potential screening programs and determine the key variables that impact program effectiveness. This model was designed to provide only an approximation of costs to easily assess the impact of key variables. Once identified, the key variables can be subjected to further testing in a precise age-adjusted model such as that developed by the Office of Technology Assessment. 4 Materials and Methods The cost-effectiveness model evaluated five possible screening programs. The assumptions used for each of the colon screening programs are summarized in Table 1. These assumptions are based on a 10-year screening period at age years. All positive test results using FOBT, sigmoidoscopy, and barium enema are evaluated with colonoscopy. When patients are found to have neoplasia, they are entered into colonoscopy surveillance. When patients have negative screening test results, the tests are repeated at the prescribed interval. Efficacy of Screening Programs Assumptions used to determine the efficacy of each program are summarized in Tables 2 and 3. The expected rates of prevalent and incident cancers (Table 2) are based on studies using screening colonoscopy 12't4-17 and the FOBT study from Minnesota. I For each screening program, the rate of cancer prevention was based on the likelihood of identifying and removing adenomatous polyps. The model assumes that ifpol- Table 1. Methods for Screening Programs Screening Frequency of program screening Method FOBT Annual screening Rehydrated FOBT slides FS Baseline examination; 55-cm examination if negative, repeat in 5 yr FS/FOBT Annual FOBT; FS 2 over 10 yr Colonoscopy One-time screening Polypectomy at time of colonoscopy Barium enema Baseline examination; Air-contrast technique if negative, repeat in 5 yr Table 2, Efficacy Assumptions Rate of cancers over 10 yr 1 Prevalent cancers (not preventable) 12'14-16 Incident cancers Mortality from cancer Undetected cancers Detected cancers 1 Prevalence of polyps Serious complications of colonoscopy 2% 0.5% 1.5% 50% 30% 35% 0.2% NOTE. Age of screenees, years; screening period, 10 years. yps are detected and removed, most cancers will be prevented.13 Prevalent cancers cannot be prevented but could be detected at an early stage. Therefore, the actual rate of cancer prevention is based on the percentage of incident cancers that could be prevented by the program (Table 3). Optimistic assumptions were used to show the maximal possible benefit for each screening program. These assumptions were later tested in the sensitivity analysis. Cost of Screening Programs The cost assumptions used in the model are summarized in Table 4. The cost assumptions are based on fee-forservice charges for all tests and are adjusted in the sensitivity analysis. The costs for colonoscopy include costs for the procedure room, nurse time and endoscopy equipment, medications, physician time, procedure monitoring, and postprocedure observation. Ifpolypectomy is performed, there is additional cost because of use of polypectomy equipment and pathology services. The model assumes that all patients with adenomas undergo two surveillance examinations during the 10 years after the baseline colonoscopy. One third of patients will have recurrent polyps at the first surveillance, requiring polypectomy. is At the second surveillance examination, the model assumes that 16% require polypectomy. Analysis The analysis was simplified by considering a 10-year screening period and calculating maximal impact of a program on colorectal cancer mortality. Cost-effectiveness was defined as the cost of preventing one death caused by colorectal cancer. Data were entered into a computer database (.IMP; SAS Institute Inc., Cary, NC) using an algebraic formula (see Appendix). Sensitivity analyses were performed to examine the impact of a range of values for the following key variables on program effectiveness and cost: patient compliance, cost of normal colonoscopy, cost of polypectomy, cost and frequency of surveillance colonoscopy, cost of cancer care, cancer detection rate, and cancer prevention rate. Results Efficacy of Screening Tests The model shows the likely maximal impact of screening on a population ofasymptomatic screenees (Ta-

3 December 1995 COLON SCREENING MODEL 1783 Table 3. Efficacy Assumptions for Screening Programs Results during lo-yr screening period FOBT alone FS alone FS/FOBT Colonoscopy Barium enema (+) Screening test Rate of colonoscopy No neoplasia Neoplasia found Rate of surveillance after polypectomy Cancer detection rate Cancer prevention rate (based on polyp detection rate) Anticipated cancers per 1000 screenees 30% 20% 40% 35% 27.5% 30% 20% 40% 100% 27.5% 20% 0% 15% 65% 10% 10% 20% 25% 35% 17.5% 10% 20% 25% 35% 17.5% 80% 60% 80% 95% 80% 30% 50% 67% 90% 50% ble 5 and Figure 1). If compliance is 100% for all tests, one-time colonoscopy achieves the greatest reduction in cancers and cancer deaths. FOBT alone prevents the fewest cancers but achieves cancer mortality reduction largely as a result of early cancer detection. The addition of flexible sigmoidoscopy (FS) to the FOBT increases the rate of cancer prevention by 2.2-fold. Barium enema has an intermediate level of efficacy. Using the model, an arbitrary rate of death reduction can be targeted, and the necessary compliance for each test can be calculated (Figure 2). For example, based on the Minnesota FOBT study, 1 maximal compliance for annual FOBT will be 75%, with an expected reduction in mortality of 35%. Compliance required for other tests needed to achieve this mortality reduction is shown in Figure 2. Cost Analysis The first cost analysis was performed assuming equal rates of compliance for all tests (Table 6). Using fee-for-service cost assumptions, the FOBT alone has a lower cost per death prevented than other programs. Figure 3 shows the proportion of costs for each phase of the screening program. The cost of cancer care represents a large proportion of the FOBT-alone program due to low rates of cancer prevention. Surveillance after polypectomy represents a large proportion of the programs using FS Table 4, Cost Assumptions $ per test FOBT 10 FS 150 Colonoscopy Normal 1000 Polypectomy 1500 Surveillance colonoscopy per 10 yr 2265 Barium enema 300 Cost of serious complication 20,000 Cost of cancer care 25,000 or colonoscopy because of enhanced polyp detection. Colonoscopy has the greatest initial cost for screening. Sensitivity Analyses The model suggests that FOBT alone is the most cost-effective program when compliance is 100% and fee-for-service charges are used. Key variables were adjusted to determine factors that impact the cost-effectiveness of each program. Cost of colonoscopy and frequency of surveillance. Figure 4 shows the impact of lower cost of colonoscopy and the effect of a reduced frequency of surveil- Table 5. Efficacy of Screening Programs Compliance % cancers % deaths (%) prevented prevented FOBT alone FSalone FOBT/FS Colonoscopy Barium enema

4 1784 DAVID A. LIEBERMAN GASTROENTEROLOGY Vol. 109, No. 6 A 100 "~ 80 "O B 100 t~ r.) 20 i 0 100% 75% 50% 0 Compliance.,. i. i. t [. 100% 75% 50% Figure 1. Efficacy of screening programs. The maximum potential benefit on (A) cancer deaths prevented and (B) cancer prevention using colonoscopy (A), FS/FOBT (1~), barium enema (&), FS (0), and FOBT (0) plotted against compliance. lance during the follow-up period for most patients. The proposed reduced frequency of surveillance (1.1 per 10 years) was calculated by assuming that 10% of patients undergoing a baseline colonoscopy examination will have polyps of 1 cm or have villous histology or carcinoma in situ. These patients would have two surveillance examinations in the 10 years after the baseline examination, and patients with small tubular adenomas would have one surveillance examination during the same period. The reduction in cost for colonoscopy and frequency of surveillance has the greatest impact on one-time screening with colonoscopy. When the cost of normal colonoscopy decreases below ~750, colonoscopy becomes costeffective relative to the other screening programs. Compliance. Figure 5 shows the impact of compliance on effectiveness. The FOBT alone is most sensitive to compliance. At 50% compliance, the cost per death prevented is similar for FOBT, FS/FOBT, and colonoscopy. The combined impact of compliance and colonoscopy cost is shown in Figure 5B. If colonoscopy costs are less than $750, one-time colonoscopy is more cost-effective than other programs at every level of compliance. Cost of cancer care. The cost of cancer care represents a large proportion of the cost of the FOBT-alone program because few cancers are actually prevented with this approach compared with the other screening tests (Figure 3). Therefore, the higher the cost of cancer care, the less cost-effective FOBT alone will be. In Figure 6, the cost of cancer care is adjusted as the key variable. As this analysis shows, when the cost of cancer care exceeds $45,000, the cost per death prevented is similar for FOBT, FS/FOBT, and colonoscopy. As the cost of cancer care increases from $25,000 to $50,000, the cost per death prevented increases by 58% for the FOBT and by only 7% for colonoscopy. FOBT cancer detection rate. The impact of modifying underlying assumptions can be assessed. For example, the assumptions used for the sensitivity of FOBT for cancer detection were based largely on one published randomized controlled trial, which used rehydrated FOBT slides. 1 In Figure 7, the impact of lower rates of cancer detection is shown. If the actual cancer detection rate is <55%, the FOBT is less cost-effective than other screening programs. If a new FOBT is developed with % Compliance Needed to Achieve Mortality Reduction , I 25 I 30 I 35 I 40 % Mortality Reduction Figure 2. Compliance and morality reduction Compliance needed to achieve a targeted level of mortality reduction for FOBT (0), FS ( ), barium enema (&), FS/FOBT ([q), and colonoscopy (A). Table 6. Cost-effectiveness % deaths Cost/ Cost/death Test prevented ($) screenee ($) prevented ($) 100% compliance FOBT ,000 FS alone ,000 FS/FOBT ,000 Colonoscopy ,000 Barium enema ,000 50% compliance FOBT ,000 FS alone ,000 FS/FOBT ,000 Colonoscopy ,000 Barium enema ,000

5 December 1995 COLON SCREENING MODEL 1785 Proportion of Total Program Cost (%) FOBT FS FS/FOBT BaE Colonoscopy Figure 3. Screening program costs. The proportion of program costs for complications (11), cancer care (~), surveillance (Eg), evaluation (E~), and screening (El). *Additional cost of polypectomy. BaE, barium enema. improved sensitivity and specificity, cost-effectiveness will be enhanced. Evaluation of positive FOBT result. The model assumed that all patients with a positive FOBT result would undergo colonoscopy. As the actual rate of compliance with evaluation of positive test results decreases, the cost-effectiveness of the FOBT is reduced (Figure 8). Cancer prevention rate. The model assumed that 90% of incident cancers could be prevented in patients undergoing colonoscopy as a result of polyp detection and removal. This assumption was based on the maximum benefit derived from polypectomy in the National Polyp Study. 13 As the cancer prevention rate attributed to polypectomy declines, each screening program becomes less cost-effective. The greatest impact is on onetime colonoscopy, which becomes more costly relative to the other screening programs. Discussion The cost-effectiveness model facilitates comparison of different colon cancer screening programs. The model can be used to assess the impact of the compliance, efficacy of tests, frequency of surveillance, and cost of procedures and cancer care on the effectiveness of each program. Based on the assumptions used in this analysis, which maximize the potential effectiveness of each test, FOBT alone is the most cost-effective method of colon cancer screening. Relatively few cancers are prevented with FOBT compared with the other screening methods. Therefore, the reduction in mortality depends on a high rate of early cancer detection. When the model is used to identify a targeted level of mortality reduction, the FOBT alone is the most cost-effective method for achieving the desired mortality reduction (Table 7). However, FOBT requires the highest level of compliance of all of the programs to achieve a targeted mortality reduction, which may limit the actual effectiveness in practice. The model shows the following key variables that have a negative impact on the cost-effectiveness of the FOBTalone program. Compliance. The model clearly shows the importance of compliance in any calculation of cost-effectiveness (Figure 3). The FOBT-alone program must have a compliance of 80% to equal the mortality reduction achieved with colonoscopy at 30% compliance and FS/ FOBT at 60% compliance. If compliance with annual FOBT is <30%, then this program is no longer superior in cost-effectiveness compared with FS/FOBT and colonoscopy. Compliance with FOBT during controlled trials has ranged from 53% to 78%. 1'19-22 However, in clinical practice, levels of compliance with one-time FOBT are much lower (13%-63%) Winawer et al. i9 noted that sustaining adherence to rescreening on an annual basis is difficult, even in a controlled trial. Therefore, achieving high compliance with annual FOBT will be difficult in clinical practice. Improved patient awareness about the benefits of screening may improve compliance. Sensitivity of FOBT for detection of colorectal cancer. The baseline assumptions for the model used data intended to maximize the efficacy of each test. The benefit of the FOBT is dependent largely on a high rate of early detected cancers. The cancer detection rate achieved in the Minnesota study may be higher than can be achieved in clinical practice or with nonrehydrated ~ 240 ~ 220 N 200 ~ 180 ~ 160 r..) 14o Normal Colon Polypectomy # Surveillance exams $1000 $1000 $750 $750 $500 $500 $1500 $1000 $1000 $1000 $1000 $ Figure 4. Cost of colonoscopy and frequency of surveillance, The impact of reduced costs for colonoscopy and/or reduced frequency of surveillance examination during a lo-year period after polypectomy for barium enema (A), colonoscopy (A), FS/FOBT (IZ), FS ( ), and FOBT (Q).

6 1786 DAVID A. LIEBERMAN GASTROENTEROLOGY Vol. 109, No. 6 A B 38 f 350 [ O i % i. i. =. I 75% 56% Compliance % 75% 50% Rgure 5. Cost-effectiveness and compliance. The impact of compliance on cost-effectiveness using two different cost assumptions. (A) In full charges, the base assumptions of the model were used. (B) In reduced cost, the following assumptions are used: normal colonoscopy, $750; polypectomy, $1000; frequency of surveillance during the 10 years after polypectomy, one examination for patient with tubular adenomas of <1 cm and two examinations for patients with large adenomas (>1 cm), villous adenomas, or carcinoma in situ. &, Barium enema; A, colonoscopy; E~, FS/FOBT,, FS; O, FOBT. FOBT slides. Other published data 26'27 suggest that the sensitivity of the FOBT for cancer detection may be 33%-50%. If the cancer detection rate is only 50%, then the model shows that colonoscopy would be more cost-effective than FOBT alone or FS/FOBT (Figure 7). Colonoscopy follow-up for positive test results. The model assumes that 100% of patients with a positive FOBT result will undergo colonoscopy. In the Minnesota FOBT study, 1 the actual rate of colonoscopy was 81%. Any reduction in the rate of colonoscopy has a significantly negative impact on the efficacy of the FOBT alone. Cost of cancer care. The FOBT alone prevents few cancers and will result in the highest rate of cancer care of all of the screening programs (Figure 3). Therefore, the cost-effectiveness of FOBT alone is quite sensitive to the cost of cancer care. In 1991, the Office of Technology Assessment conservatively estimated the cost of treating early cancer to be $20,000 and late cancer to be $30,000. Therefore, it is likely that current true costs exceed $25,000 per cancer case, which was used in the baseline assumptions for model. If the cost of cancer care exceeds $45,000, FS/FOBT and colonoscopy are more cost-effective than FOBT alone. Cost of colonoscopy. If the cost of normal colonoscopy is $750, as in the reduced cost model, one-time colonoscopy is a more cost-effective screening program than FOBT alone at equal levels of compliance. The American Cancer Society has long recommended combining the FOBT and FS for screening of asymptomatic subjects. The potential benefits and costs of the addition of FS to the FOBT can be assessed using the model. At every level of compliance, there is a marked increase in the number of deaths prevented (32% increase). The additional mortality reduction is achieved primarily through cancer prevention (i.e., polyp detection and removal). The addition of FS to FOBT results in a 2.2- fold increase in cancers prevented (22.5% vs. 50%). Despite the superior efficacy, the FS/FOBT method is more costly per death prevented. Several factors enhance the cost-effectiveness of the FS/FOBT relative to FOBT alone. If compliance for the FOBT is <50%, or the cost of cancer care exceeds $45,000, or the cost of colonoscopy is less than $750, the combined FS/FOBT becomes more cost-effective than FOBT alone. Sigmoidoscopy alone has a similar level of cost-effectiveness as combined screening with FS/FOBT and prevents fewer deaths. The model suggests that if used as a single test, a sigmoidoscopy program would prevent more cancer deaths than FOBT alone but at a higher cost. The model finds that barium enema would not be cost-effective relative to the other screening programs. Despite high rates of cancer detection, the relatively poor rate of polyp detection and the need to evaluate falsepositive test results with colonoscopy increases the program costs.

7 December 1995 COLON SCREENING MODEL ~ 320 N 300 O ~ 280 e~ > 3OO ~ 240 o r..) 220 ~ 220, I i I I 25j)00 30,000 40,000 50, Cost of Cancer Care ($) Compliance with Colonoscopic Evaluation after (+) FOBT Figure 6. Cost of cancer care. The impact of variable cost of cancer care on the cost-effectiveness of barium enema (A), colonoscopy (A), FS/FOBT (F1), FS ( ), and FOBT (0). Figure 8. Evaluation of positive FOBT result. The impact of variable rates of colonoscopic follow-up to evaluate a positive FOBT result for cotonoscopy (~), FS/FOBT (C]), and FOBT (0). Some experts believe that screening with colonoscopy will be the most effective way to reduce colon cancer mortality. The model shows that the efficacy of colonoscopy is sensitive to assumptions regarding the cancer prevention rate associated with polyp detection and removal. The model assumed that colonoscopy could prevent 90% of incident cancers in patients who undergo this examination. If the actual cancer prevention rate is lower, colonoscopy becomes less cost-effective relative to other screening programs. However, all screening programs would have a decline in cost-effectiveness as the benefits attributed to polypectomy decline. The model shows that one-time colonoscopy has the greatest impact on colorectal cancer mortality and would be cost-effective if the cost of normal colonoscopy is less ~. 300 g,~ 280 " 260 #: N 240 O ~ 220 O r.) &, &,,,t" -- &, A, %U ' ' 65%' ' ' 5k%u FOBT Cancer Detection Rate Figure 7. FOBT cancer detection rate. The impact of variable levels of FOBT sensitivity for cancer detection on the cost-effectiveness of barium enema (A), colonoscopy (A), FS/FOBT ([3), FS ( ), and FOBT (O). than $750. Colonoscopy screening is very sensitive to the cost of colonoscopy compared with the other tests (Figure 4). If health care planners can devise ways to reduce the true costs of colonoscopy and convince patients to undergo one-time screening, then this approach will indeed be the most effective. This will require careful analysis of colonoscopy costs and public education. One argument against screening with colonoscopy is concern that compliance would be unacceptably low. Onetime screening with colonoscopy requires 44% compliance to reach the 35% mortality reduction level. However, it may be argued that compliance with a one-time test like colonoscopy may be more readily achieved that sustained compliance with an annual test like FOBT. Compliance with screening colonoscopy was very low when offered to asymptomatic subjects in a mailing. 12 If physicians offer colonoscopy screening as part of a comprehensive preventive health strategy, compliance may be improved, although this has never been evaluated in a study. When physicians counsel patients to undergo colonoscopy after Table 7. Cost of Achieving Targeted Mortality Reduction Compliance and cost to achieve 35% mortality reduction 25% mortality reduction Cost/death Cost/death % of prevented % of prevented compliance ($) compliance ($) FOBT , ,000 FSalone , ,000 FS/FOBT , ,000 Colonoscopy , ,000 Barium enema , ,000

8 1788 DAVID A. LIEBERMAN GASTROENTEROLOGY Vol. 109, No. 6 Appendix: Cost Formula Assumptions 20 cancers/lo00 screenees over 10 years Prevalent cancers = 5 Incident (i.e., preventable) cancers = 15 No. of deaths with no screening = 10 (50%) Efficacy of screening Prevalent cancers (n = 5) 5 x % compliance = c 5 - c = d (undetected cancers) 0.5 (mortality) c x (% detected cancers) = e (detected cancers) x 0.3 (mortality) c x (% cancers not detected) = f (undetected cancers) x 0.5 (mortality) Incident cancers (n = 15) 15 x % complicance = k 15 - k = m (undetected cancers) x 0.5 (mortality) k x (% prevented cancers) = C (cancers prevented) k - I = o (incident cancers in screened patients) o x (% cancers detected) = p x 0.3 (mortality) o x (% cancers undetected) = r x 0.5 (mortality) No. of deaths=g+h +i+n + q +s No. of cancers = 20 - C Deaths =g =h =i =n =q =S Cost of screening S/test Total $ for 1000 eligible screenees (-) screening test 1000 x compliance x % (-) test (+) screening test 1000 x compliance x % (+) test (w) Normal colonoscopy vv x (% with no polyps) = w Polypectomy vv x (% with polyps) = y Surveillance #1 w X (% with recurrent polyps) = ww w x (% with no recurrent polyps) = yy Surveillance #2 = zz No. of colonoscopies w+y+ww +yy+zz=aa Complications AA X = No. of cancers 20 - C = Total cost per 1000 screenees ii +jj+ kk+ II + mm + nn +oo + pp x aa x bb x cc x dd x dd X cc x gg (cost of complication) hh (cost of cancer care) = ii =jj = kk = II = mm = nn = O0 = pp = qq Cost-effectiveness Cost per eligible screenee = qq/lo00 Cost per death prevented = qq/(lo - no. of deaths) Cost per cancer prevented = qq/c a positive FOBT result, patient compliance has been as high as 81%.1 Therefore, the impact of physician recommendations cannot be underestimated. The model permits analysis of cost-effectiveness based on anticipated compliance in a clinical setting. An ongoing Veterans Affairs Cooperative Study will evaluate compliance with screening colonoscopy in VA general medicine clinics. 28 This model shows the trade-offs that must be made by managed health care systems that are considering offering some form of colon cancer screening to their enrollees. In some cases, choosing the less costly option will result in higher rates of cancer and higher mortality from colon cancer among subscribers. The analysis also points out an interesting paradox. If colonoscopy can be performed for $750, then colonoscopy screening has the lowest cost per death prevented of all of the programs. However, the per-screenee cost for colonoscopy is higher than for FOBT alone ($1388 vs. $834). Therefore, man-

9 December 1995 COLON SCREENING MODEL 1789 agers may prefer to use the test with lower per-screenee cost, which results in short-term savings, although it is less cost-effective in terms of cost per death prevented. The model can also be used to determine the relative cost impact of the initial screening test, the evaluation of positive results, repetition of tests in patients with negative screening, surveillance, and complications (Figure 3). This information may prove useful to health care planners trying to identify ways to reduce the cost of screening with minimal impact on efficacy. Surveillance accounts for 19%-34% of screening costs when performed twice during the follow-up period. This is reduced to 11%-20% if surveillance can be reduced to one examination for the patients with polyps that are < 1 cm. The model can be used to determine important areas for investigation (i.e., frequency of surveillance) that will have an impact on cost-effectiveness. Finally, the assumptions used in the model can also be applied to calculate the cost of no screening at all. The model assumes that without screening, there will be 20 cancers and 10 cancer deaths/1000 potential screenees during a period of 10 years. If the average cost of cancer care is $25,000, then the cost of providing care to 1000 patients (age, years) during a period of 10 years without any screening will be $677 per potential screenee. If the cost of cancer care is $50,000 because of late cancer detection, then the 10-year cost per person of no screening exceeds $1000. For managed health care systems, this may represent an incentive to consider screening their enrollees. In conclusion, this model for analyzing the cost of colon screening programs can identify key variables that impact the cost-effectiveness of the program. Based on assumptions that maximize the effectiveness of each program, the FOBT-alone program is more cost-effective than other programs. However, the FOBT program is very sensitive to key variables, including the FOBT cancer detection rate, cost of cancer care, cost of colonoscopy, and compliance with colon evaluation of a positive FOBT result. Perhaps the most important variable in any program will be patient compliance. Despite evidence that screening can substantially reduce the risk of death from colon cancer, compliance with screening in the United States is poor. Future study should be focused on methods of patient education that will improve patient compliance with screening. References 1. Mandel JS, Bond JH, Church TR, Snover DC, Bradley GM, Schuman LM, Ederer F. Reducing mortality from colorectal cancer by screening for fecal occult blood. N Engl J Med 1993;328: Selby JV, Friedman GD, Quesenberry CP Jr, Weiss NS. A casecontrol study of screening sigmoidoscopy and mortality from colorectal cancer. N Engl J Med 1992;326: Newcomb PA, Norfleet RG, Storer BE, Surawicz TS, Marcus PM. Screening sigmoidoscopy and colorectal cancer mortality. J Natl Cancer Inst 1992;84: Wagner JL, Herdman RC, Wadhwa S. Cost effectiveness of colorectal cancer screening in the elderly. Ann Intern Med 1991; 115: Ransohoff DF, Lang CA, Kuo HS. Colonoscopic surveillance after polypectomy: considerations of cost effectiveness. Ann Intern Med 1991; 114: Eddy DM. Screening for colorectal cancer. Ann Intern Med 1990; 113: Barry M J, Mulley AG, Richter JM. Effect of workup strategy on the cost-effectiveness of fecal occult blood screening for colorectal cancer. Gastroenterology 1987; 93: Lieberman D. Cost-effectiveness of colon cancer screening. Am J Gastroenterol 1991;86: Byers T, Gersky R. Estimates of costs and effects of screening for colorectal cancer in the United States. Cancer 1992;70: Levin B, Murphy GP. Revision in American Cancer Society recommendations for the early detection of colorectal cancer. CA Cancer J Clin 1992;42: Winawer S J, Flehinger B J, Schottenfeld D, Miller DG. Screening for colorectal cancer with fecal occult blood testing and sigmoidoscopy. J Natl Cancer Inst 1993;85: Rex DK, Lehman GA, UlbrightTM, Smith J J, Pound DC, Hawes RH, Helper D J, Wiersema M J, Langefeld CD Li W. Colonic neoplasia in asymptomatic persons with negative fecal occult blood tests: influence of age, gender, and family history. Am J Gastroenterol 1993;88: Winawer S J, Zauber AG, Ho MN, O'Brien M J, Got/lieb LS, Sternberg SS, Waye JD, Schapiro M, Bond JH, Panish JF, Ackroyd F, Shike M, Kurtz RC, Hornsby-Lewis L, Gerdes H, Stewart ET. Prevention of colorectal cancer by colonoscopic polypectomy. N Engl J Med 1993;329: Foutch PG, Mai H, Pardy K, Disario J, Manne RK, Kerr D. Flexible sigmoidoscopy may be ineffective for secondary prevention of colorectal cancer in asymptomatic, average-risk men. Dig Dis Sci 1991;36: Johnson DA, Gurney MS, Volpe R J, Jones DM, Van Ness MM, Chobarian S J, Avalos JC, Buck JL, Kooyman G, Cattan EL. A prospective study of the prevalence of colonic neoplasms in asymptomatic patients with an age-related risk. Am J Gastroenterol 1990;85: Lieberman DA, Smith FW. Screening for colon malignancy with colonoscopy. Am J Gastroenterol 1991;86: Guillem JG, Forde KA, Treat MR, Neugut AI, O'Toole KM, Diamond BE. Cotonoscopic screening for neoplasms in asymptomatic firstdegree relatives of colon cancer patients. Dis Colon Rectum 1992; 35: Winawer S J, Zauber AG, O'Brien M J, Ho MN, Gottlieb L, Sternberg SS, Waye JD, Bond J, Schapiro M, Stewart ET, Panish J, Ackroyd F, Kurtz RC, Shike M. Randomized comparison of surveillance intervals after colonoscopic removal of newly diagnosed adenomatous polyps. N Engl J Med 1993;328: Winawer S J, Schottenfeld D, Flehinger BJ. Colorectal cancer screening. J Natl Cancer Inst 1991;83: Kewenter J, Brevinge H, Engaras B, Haglind E, Ahren C. Results of screening, rescreening, and follow-up in a prospective randomized study for detection of colorectal cancer by fecal occult blood testing. Results for 68,308 subjects. Scand J Gastroenterol 1994; 29: Hardcastle JD, Chamberlain J, Sheffield J, Balfour TW, Armitage

10 1790 DAVID A. LIEBERMAN GASTROENTEROLOGY Vol. 109, No. 6 NC, Thomas WM, Pye G, James PD, Amar SS, Moss SM. Randomised, controlled trial of faecal occult blood screening for colorectal cancer. Results for first 107,349 subjects. Lancet 1989; 1: Kronborg O, Fenger C, OIsen J, Bech K, Sondergaard O. Repeated screening for colorectal cancer with fecal occult blood test. A prospective randomized study at Funen, Denmark. Scand J Gastroenterol 1989;24: Bralow SP, Kopel J. Hemoccuit screening for colorectal cancer: an impact study in Sarasota, Florida. J Fia Med Assoc 1979;66: McGarrity T J, Long PA, Peiffer LP. Results of a repeat televisionadvertised mass screening program for colorectal cancer using fecal occult blood tests. Am J Gastroentero11990;85: Sontag S, Durczak C, Aranha G, Chejfec G, Frederick W, Greenlee H. Fecal occult blood screening for colorectal cancer in a Veterans Administration hospital. Am J Surg 1983; 145: Allison JE, Feldman R, Tekawa IS. Hemoccult screening in detecting colorectal neoplasm: sensitivity, specificity, and predictive value. Long-term follow-up in a large group practice setting. Ann intern Med 1990;112: Ahlquist DA, Wieand HS, Moertel CG, McGill DB, Loprinzi CL, O'Connell M J, Mailliard JA, Gerstner JB, Pandya K, Ellefson RD. Accuracy of fecal occuld blood screening for colorectal neoplasia. A prospective study using Hemoccult and HemoQuant tests. JAMA 1993; 269: Lieberman D. Prospective evaluation of risk factors for large (->1 cm) colonic adenomas in asymptomatic subjects. V.A. Cooperative Studies Program Update, December 1994-May Received June 2, Accepted August 16, Address requests for reprints to: David A. Lieberman, M.D., Gastroenterology Section, Portland Veterans Affairs Medical Center 111A, P.O. Box 1034, Portland, Oregon Fax: (503)