Cost-effectiveness analysis of colorectal cancer screening with stool DNA testing in intermediate-incidence countries Wu G H, Wang Y W, Yen A M, Wong J M, Lai H C, Warwick J, Chen T H Record Status This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. Health technology The present study compared screening strategies for the early identification of colorectal cancer (CRC). Specifically, it compared 3-, 5- and 10-yearly stool deoxyribonucleic acid (DNA) testing (DNA3, DNA5 and DNA10), with annual faecal occult blood testing (FOBT1), 5-yearly flexible sigmoidoscopy (SIGM5), 10-yearly colonoscopy (COLO10) and no screening (NoS). Stool DNA testing analyses the DNA contained in stools, through natural exfoliation, and detects alterations. Type of intervention Screening. Economic study type Cost-effectiveness analysis. Study population The base-case population for the model consisted of a cohort of 100,000 asymptomatic adults aged 50 years who were at average risk of developing CRC. Setting The setting was primary and secondary care. The economic study was carried out in Taiwan. Dates to which data relate The studies providing the effectiveness evidence dated from 1987 to 2004. For the cost data, the date was 2004. The price year was 2004. Source of effectiveness data The effectiveness data were derived from published studies. Modelling A computer simulation state transition Markov model was used to simulate the natural history of CRC and to estimate the cost and effectiveness of screening strategies during a 25-year time horizon. In each annual cycle of the model, each person in the cohort was assumed to transit among the following health states: normal, small adenoma (adenoma smaller than 1 cm in size), Page: 1 / 6
large adenoma (adenoma larger than 1 cm in size), preclinical early CRC (preclinical Dukes' Stage A and B CRC), preclinical late CRC (preclinical Dukes' Stage C and D), clinical early CRC, clinical late CRC, CRC death, and other cause of death. The initial state could be normal, adenoma, or preclinical CRC with the corresponding prevalence rates at age 50 years. The assumptions of the model were well described. Outcomes assessed in the review The clinical parameters considered in the model were: the sensitivity and specificity of the screening tests; the prevalence of colorectal neoplasms at age 50 years; the annual transition rates between the health states by age; flexible sigmoidoscopy reach; compliance and referral rates; complications of colonoscopy including perforation rate, and death rate due to perforation. Study designs and other criteria for inclusion in the review No inclusion criteria were specified. The study designs included in the review were not described. Sources searched to identify primary studies Criteria used to ensure the validity of primary studies Methods used to judge relevance and validity, and for extracting data Number of primary studies included The authors reported that 27 primary studies were included in the review. Page: 2 / 6
Methods of combining primary studies A narrative method was used to combine the studies. Investigation of differences between primary studies Results of the review Base-case estimates were reported with the corresponding ranges used in the sensitivity analysis and bibliographic references. The outcomes were as follows. The prevalence of colorectal neoplasms at age 50 years was 9.28% for small adenoma, 3.82% for large adenoma, 0.12% for preclinical early CRC, and 0.08% for preclinical late CRC. The annual transition rate from normal to small adenoma was 0.00836 at age 50 years, 0.00990 at age 55 years, 0.01156 at age 60 years, 0.01333 at age 65 years, and 0.01521 at age 70 years. The annual transition rate was: from small adenoma to large adenoma, 0.0346; from large adenoma to preclinical early CRC, 0.0215; from preclinical early CRC to preclinical late CRC, 0.3697; from preclinical early CRC to clinical early CRC, 0.2382; from preclinical late CRC to clinical late CRC, 0.4852; from early CRC to CRC death, 0.0302; and from late CRC to CRC death, 0.2099. The flexible sigmoidoscopy reach was 50 cm. The sensitivity of stool DNA testing was 8% for small adenoma, 15% for large adenoma, and 52% for preclinical CRC. The sensitivity of FOBT was 5% for small adenoma, 10% for large adenoma, and 50% for preclinical CRC. The sensitivity of flexible sigmoidoscopy and colonoscopy was 78.5% for small adenoma, 85% for large adenoma, and 95% for preclinical CRC. Specificity was 94% for stool DNA testing, 97.5% for FOBT, 94% for flexible sigmoidoscopy, and 98% for colonoscopy. Complications of colonoscopy included a rate of 0.2% for perforation and a rate of 10 per 100,000 for deaths due to perforation. Compliance rates were assumed to be 60% for FOBT and stool DNA testing, and 40% for sigmoidoscopy and colonoscopy. The referral rate to diagnostic colonoscopy after positive findings with screening was assumed to be 85%. Page: 3 / 6
Measure of benefits used in the economic analysis The measure of benefits used was the additional life-years (LYs) gained as a result of screening. The LYs were discounted to the present value at an annual rate of 3%. Direct costs Health service direct costs were included in the analysis and were appropriately discounted at a rate of 3% per year. Such costs included the costs relating to the screening itself, treatment and diagnostic tests (adenoma and CRC only), complications from colonoscopy and surveillance (adenoma only). All estimates of cost, except for stool DNA testing, were based on Medicare Payments by the Bureau of National Health Insurance. The cost of stool DNA testing was estimated by experts after considering the cost of the required laboratory manpower and relevant materials in Taiwan. The lifetime costs for CRC encompassed the initial costs relating to surgery, chemotherapy and radiotherapy, the continuing costs of follow-up after potentially curative therapy, and the eventual cost of terminal care. For the purposes of this costing, expenditure on terminal care was only included for those who died from CRC (in the model). For early CRC, the initial cost included only surgery. Estimations of the quantities and total costs were derived using modelling. The resource quantities and the costs were not reported separately. The price year was 2004. Statistical analysis of costs The costs were treated deterministically and no statistical tests were carried out. Indirect Costs The authors' stated perspective was that of a third-party payer. Therefore, appropriately, no indirect costs were included in the study. Currency US dollars ($). The exchange rate was $1 = 34 New Taiwanese dollars in 2004. Sensitivity analysis Sensitivity analyses were performed to assess the robustness of the results. The parameters evaluated were the prevalence of colorectal neoplasms at age 50 years, the transition rates, the sensitivity and specificity of the screening tests, the cost per unit of stool DNA testing, compliance with screening, the referral rate to diagnostic colonoscopy, and the cost of treatment. One-way and threshold analyses were used. In addition, scenario analyses were conducted to assess the impact of the sensitivity of stool DNA testing strategy because of its variability. The ranges for the sensitivity analyses were reported and were taken from published sources. Estimated benefits used in the economic analysis The life expectancy (by strategy) was 15.7337 years for NoS, 15.7476 years for DNA3, 15.7434 years for DNA5, 15.7400 years for DNA10, 15.7584 years for FOBT1, 15.7477 years for SIGM5, and 15.7590 years for COLO10. The incremental LYs saved(by strategy) for a 100,000 persons cohort were 0 for NoS, 1,390 for DNA3, 970 for DNA5, 626 for DNA10, 2,464 for FOBT1, 1,383 for SIGM5, and 2,530 for COLO10. Cost results The total costs (by strategy) were $22,022 for NoS, $35,637 for DNA3, $31,077 for DNA5, $26,856 for DNA10, $19,824 for FOBT1, $24,909 for SIGM5, and $21,843 for COLO10. The incremental costs were $0 for NoS, $13,615 for DNA3, $9,054 for DNA5, $4,834 for DNA10, -$2,198 for FOBT1, $2,887 for SIGM5, and -$180 for COLO10. Page: 4 / 6
Synthesis of costs and benefits The authors calculated incremental cost-effectiveness ratios for each screening strategy compared with no screening. However, the important result was that FOBT1 and COLO10 dominated all the other screening strategies. This means that they were both more effective and less costly than the other strategies. Unfortunately, the authors did not calculate the incremental cost-effectiveness of COLO10 compared with FOBT1. None of the sensitivity analyses appear to have shown any change in the main results. Authors' conclusions The results suggested that stool deoxyribonucleic acid (DNA) testing was less cost-effective than other currently recommended strategies for the population-based screening of average risk individuals in a country with an intermediate incidence of CRC. CRD COMMENTARY - Selection of comparators The authors justified their choice of the comparators. They compared the most common screening methods with stool DNA testing, which had not often been considered in economic studies as a screening tool for use in the general population in countries with low or intermediate incidence of CRC. You should judge whether these screening methods are relevant in your own setting, or whether other comparators could also have been relevant. Validity of estimate of measure of effectiveness The authors used data only from published sources. The main sources of effectiveness evidence were randomised controlled trials and meta-analyses, which are adequate sources from which to estimate effectiveness. The authors conducted a review of the literature, but there was no indication that it was systematic. The methodology for selecting and reviewing the literature used was not reported. The authors used data from the primary studies selectively. The estimates were investigated using sensitivity analyses, and the justification for the ranges selected was also based on the medical literature. Validity of estimate of measure of benefit The measure of benefits used in the economic analysis was the LYs gained. It was derived from the model described previously. The choice of the measure of benefit seems reasonable given the disease in question. You should ask yourself if there are significant quality of life outcomes to consider as well. Validity of estimate of costs The authors reported that the costs were estimated from the perspective of a third-party payer. As such, all the relevant cost categories appear to have been included. The costs and the quantities were not reported separately, which would make it difficult to rework the analysis in other settings. The source of the cost data was appropriate for the perspective adopted. Sensitivity analyses of the costs were conducted to assess the robustness of the estimates used. Given that the time horizon of the model was longer than 2 years, discounting was appropriately carried out. The price year was reported, which will aid any future reflation exercises. Other issues The authors compared their findings with those from other studies which, in general, showed consistency. In addition, the model was validated against the observed incidence of CRC in Taiwan. However, the generalisability of the results to other settings was not addressed. The authors' conclusions reflected the scope of the analysis. Although the authors' primary concern was the cost-effectiveness of stool screening, it would have been useful had they calculated an incremental cost-effectiveness ratio comparing the two dominant strategies. The authors acknowledged, as a limitation to their study, that the proposed model assumed an adenoma to carcinoma sequence which accounted for the majority of CRCs; non-polypoid cases were not taken into account. However, as only a fraction of CRCs are non-polypoid and the cost-effectiveness analysis addressed the relative comparisons across screening strategies, the incorporation of the Page: 5 / 6
Powered by TCPDF (www.tcpdf.org) occurrence of non-polypoid tissue would be unlikely to substantially affect the results. Implications of the study Opting for colonoscopy as a screening tool for average-risk groups might be questionable given the shortage of medical endoscopic manpower and the risk of perforation associated with colonoscopy. Stool DNA testing would be preferable to the other screening strategies if the sensitivity for both adenoma and CRC were sufficiently high, as seen in the bestcase scenario of the sensitivity analysis, and if the cost of the test could be lowered through economies of scale. However, the interpretation of the finding in the best-case scenario should be treated with some caution since it was carried out using data derived from studies based on clinical series rather than asymptomatic individuals from an average-risk population. Source of funding None stated. Bibliographic details Wu G H, Wang Y W, Yen A M, Wong J M, Lai H C, Warwick J, Chen T H. Cost-effectiveness analysis of colorectal cancer screening with stool DNA testing in intermediate-incidence countries. BMC Cancer 2006; 6:136 Original Paper URL http://www.biomedcentral.com/content/pdf/1471-2407-6-136.pdf Other publications of related interest Because readers are likely to encounter and assess individual publications, NHS EED abstracts reflect the original publication as it is written, as a stand-alone paper. Where NHS EED abstractors are able to identify positively that a publication is significantly linked to or informed by other publications, these will be referenced in the text of the abstract and their bibliographic details recorded here for information Indexing Status Subject indexing assigned by NLM MeSH Colonoscopy /economics; Colorectal Neoplasms /diagnosis /economics /epidemiology /genetics; Cost-Benefit Analysis; DNA, Neoplasm /analysis; Feces /chemistry; Health Care Costs /statistics & numerical data; Humans; Incidence; Markov Chains; Mass Screening /economics /methods; Occult Blood; Quality-Adjusted Life Years; Sigmoidoscopy /economics AccessionNumber 22006001760 Date bibliographic record published 31/03/2007 Date abstract record published 31/03/2007 Page: 6 / 6