Wilschut, J.A.

Health Effects and Costs of Colorectal Cancer Screening (Doctoral Thesis)

2012-04-18T00:00:00Z

Colorectal cancer (CRC) is a major public health problem, with over a million newly diagnosed cases per year worldwide. CRC occurs especially frequently in established market economies like Europe, the United States (US), Canada, Australia and Japan. The lifetime incidence in average risk individuals in these regions is approximately 5%. CRC incidence steeply increases with age, and it is higher in men than in women. At young ages, CRC is rare, and often associated with a genetic predisposition. In the US, the CRC incidence has been decreasing and is now lower than in the Netherlands. In the Netherlands, the number of newly diagnosed CRC cases has increased to 12,000 per year, accounting for 5,000 deaths per year. This makes CRC the second leading cause of cancer death for men and the third for women in the Netherlands.

Fecal occult blood testing when colonoscopy capacity is limited (Article)

2011-12-07T00:00:00Z

Background Fecal occult blood testing (FOBT) can be adapted to a limited colonoscopy capacity by narrowing the age range or extending the screening interval, by using a more specific test or hemoglobin cutoff level for referral to colonoscopy, and by restricting surveillance colonoscopy. Which of these options is most clinically effective and cost-effective has yet to be established. Methods We used the validated MISCAN-Colon microsimulation model to estimate the number of colonoscopies, costs, and health effects of different screening strategies using guaiac FOBT or fecal immunochemical test (FIT) at various hemoglobin cutoff levels between 50 and 200 ng hemoglobin per mL, different surveillance strategies, and various age ranges. We optimized the allocation of a limited number of colonoscopies on the basis of incremental cost-effectiveness. Results When colonoscopy capacity was unlimited, the optimal screening strategy was to administer an annual FIT with a 50 ng/mL hemoglobin cutoff level in individuals aged 45-80 years and to offer colonoscopy surveillance to all individuals with adenomas. When colonoscopy capacity was decreasing, the optimal screening adaptation was to first increase the FIT hemoglobin cutoff value to 200 ng hemoglobin per mL and narrow the age range to 50-75 years, to restrict colonoscopy surveillance, and finally to further decrease the number of screening rounds. FIT screening was always more cost-effective compared with guaiac FOBT. Doubling colonoscopy capacity increased the benefits of FIT screening up to 100%. Conclusions FIT should be used at higher hemoglobin cutoff levels when colonoscopy capacity is limited compared with unlimited and is more effective in terms of health outcomes and cost compared with guaiac FOBT at all colonoscopy capacity levels. Increasing the colonoscopy capacity substantially increases the health benefits of FIT screening.

Cost-effectiveness analysis of a quantitative immunochemical test for colorectal cancer screening (Article)

2011-11-01T00:00:00Z

Background & Aims: Two European randomized trials (N = 30,000) compared guaiac fecal occult blood testing with quantitative fecal immunochemical testing (FIT) and showed better attendance rates and test characteristics for FIT. We aimed to identify the most cost-effective FIT cutoff level for referral to colonoscopy based on data from these trials and allowing for differences in screening ages. Methods: We used the validated MIcrosimulation SCreening ANalysis (MISCAN)-Colon microsimulation model to estimate costs and effects of different screening strategies for FIT cutoff levels of 50, 75, 100, 150, and 200 ng/mL hemoglobin. For each cutoff level, screening strategies were assessed with various age ranges and screening intervals. We assumed sufficient colonoscopy capacity for all strategies. Results: At all cost levels, FIT screening was most effective with the 50 ng/mL cutoff level. The incremental cost-effectiveness ratio of biennial screening between ages 55 and 75 years using FIT at 50 ng/mL, for example, was 3900 euro per life year gained. Annual screening had an incremental cost-effectiveness ratio of 14,900 euro per life year gained, in combination with a wider age range (between ages 45 and 80 years). In the sensitivity analysis, 50 ng/mL remained the preferred cutoff level. Conclusions: FIT screening is more cost-effective at a cutoff level of 50 ng/mL than at higher cutoff levels. This supports the recommendation to use FIT at a cutoff level of 50 ng/mL, which is considerably lower than the values used in current practice.

How much colonoscopy screening should be recommended to individuals with various degrees of family history of colorectal cancer? (Article)

2011-09-15T00:00:00Z

BACKGROUND: Individuals with a family history of colorectal cancer (CRC) are at increased risk for CRC. Current screening recommendations for these individuals are based on expert opinion. The authors investigated optimal screening strategies for individuals with various degrees of family history of CRC based on a cost-effectiveness analysis. METHODS: The MISCAN-Colon microsimulation model was used to estimate costs and effects of CRC screening strategies, varying by the age at which screening was started and stopped and by screening interval. The authors defined 4 risk groups, characterized by the number of affected first-degree relatives and their age at CRC diagnosis. For all risk groups, the optimal screening strategy had an incremental cost-effectiveness ratio of approximately $50,000 per life-year gained. RESULTS: The optimal screening strategy for individuals with 1 first-degree relative diagnosed after age 50 years was 6 colonoscopies every 5 years starting at age 50 years, compared with 4 colonoscopies every 7 years starting at age 50 years for average risk individuals. The optimal strategy had 10 colonoscopies every 4 years for individuals with 1 first-degree relative diagnosed before age 50 years, 13 colonoscopies every 3 years for individuals with 2 or more first-degree relatives diagnosed after age 50 years, and 15 colonoscopies every 3 years for individuals with 2 or more first-degree relatives of whom at least 1 was diagnosed before age 50 years. CONCLUSIONS: The optimal screening strategy varies considerably with the number of affected first-degree relatives and their age of diagnosis. Shorter screening intervals than the currently recommended 5 years may be appropriate for the highest risk individuals.

Advance notification letters increase adherence in colorectal cancer screening: A population-based randomized trial (Article)

2011-06-01T00:00:00Z

Objective: The population benefit of screening depends not only on the effectiveness of the test, but also on adherence, which, for colorectal cancer (CRC) screening remains low. An advance notification letter may increase adherence, however, no population-based randomized trials have been conducted to provide evidence of this. Method: In 2008, a representative sample of the Dutch population (aged 50-74. years) was randomized. All 2493 invitees in group A were sent an advance notification letter, followed two weeks later by a standard invitation. The 2507 invitees in group B only received the standard invitation. Non-respondents in both groups were sent a reminder 6. weeks after the invitation. Results: The advance notification letters resulted in a significantly higher adherence (64.4% versus 61.1%, p-value 0.019). Multivariate logistic regression analysis showed no significant interactions between group and age, sex, or socio-economic status. Cost analysis showed that the incremental cost per additional detected advanced neoplasia due to sending an advance notification letter was €957. Conclusion: This population-based randomized trial demonstrates that sending an advance notification letter significantly increases adherence by 3.3%. The incremental cost per additional detected advanced neoplasia is acceptable. We therefore recommend that such letters are incorporated within the standard CRC-screening invitation process.

Diagnostic Yield Improves With Collection of 2 Samples in Fecal Immunochemical Test Screening Without Affecting Attendance (Article)

2011-04-01T00:00:00Z

Background & Aims: The fecal immunochemical test (FIT) is superior to the guaiac-based fecal occult blood test in detecting neoplasia. There are not much data on the optimal number of FITs to perform. We conducted a population-based trial to determine attendance and diagnostic yield of 1- and 2-sample FIT screening. Methods: The study included 2 randomly selected groups of subjects aged 50-74 years (1-sample FIT, n = 5007; 2-sample FIT, n = 3197). The 2-sample group was instructed to collect fecal samples on 2 consecutive days. Subjects were referred for colonoscopy when at least 1 sample tested positive (≥50 ng hemoglobin/mL). Results: Attendance was 61.5% in the 1-sample group (2979 of 4845; 95% confidence interval, 60.1%-62.9%) and 61.3% in the 2-sample group (1875 of 3061; 95% confidence interval, 59.6%-63.0%; P = .84). In the 1-sample group 8.1% tested positive, and in the 2-sample group 12.8% had at least 1 positive test outcome and 5.0% had 2 positive test outcomes (P < .05). When the mean from both test results in the 2-sample group was used, 10.1% had a positive test outcome (P < .05). The detection rates for advanced neoplasia were 3.1% in the 1-sample group, 4.1% in the 2-sample group with at least 1 positive test outcome, 2.5% when both test results were positive, and 3.7% among subjects with the mean from both test results being positive. Conclusions: There is no difference in attendance for subjects offered 1- or 2-sample FIT screening. The results allow for the development of efficient FIT screening strategies that can be adapted for local colonoscopy capacities, rather than varying the cut-off value in a 1-sample strategy.

Increased risk of adenomas in individuals with a family history of colorectal cancer: results of a meta-analysis (Article)

2010-12-01T00:00:00Z

Objective: It is unclear to what extent the increased risk of colorectal cancer in individuals with a family history of colorectal cancer and no known genetic disorders is associated with a higher adenoma prevalence. Our aim is to estimate the relative difference in adenoma prevalence and its age-pattern in individuals with a family history of colorectal cancer compared to those without. Methods: We performed a literature search to identify colonoscopy studies reporting the adenoma prevalence by age. Using multilevel logistic regression, we examined how the adenoma prevalence by age differed between individuals with and without a family history of colorectal cancer. We excluded members of families with a known genetic disorder. Results: Thirteen colonoscopy studies were identified. The adenoma prevalence was significantly higher in individuals with a family history than in those without (OR 1.7, 95% CI 1.4-3.5). The adenoma prevalence increased with age (OR per year of age 1.06, 95% CI 1.05-1.07). The age trend did not differ significantly between the two groups. Conclusion: Individuals with a family history of colorectal cancer have a considerably higher prevalence of adenomas compared to individuals without a family history. This is consistent with their increased risk of colorectal cancer.

A Decision-Analytic Evaluation of the Cost-Effectiveness of Family History-Based Colorectal Cancer Screening Programs (Article)

2010-08-01T00:00:00Z

OBJECTIVES:The aim of this study was to determine the cost-effectiveness of family history screening (FHS) for colorectal cancer (CRC) susceptibility at age 40 with early screening of those with increased risk.METHODS:The cost-effectiveness of several family history-based screening programs was estimated with a validated microsimulation model, using data from the SEER cancer registry, life tables, medicare records, and published data. Familial cancer syndromes were excluded. Screening programs evaluated included (i) colonoscopy screening every 10 years starting at age 50 (no family history assessment); (ii) colonoscopy every 10 years from age 40 for persons with a family history; (iii) colonoscopy every 5 years from age 50 for those with a family history; and (iv) colonoscopy every 5 years from age 40 for persons with a family history. In each FHS scenario, persons without a family history are screened with colonoscopy at age 50, then every 10 years to age 80.RESULTS:Compared with colonoscopy screening of all persons from age 50, the cost-effectiveness of the family history-based screening programs varied from $18,000-$51,000 per life year (LY) gained. Screening family history cases every 5 years from age 40 is more cost-effective than screening every 10 years from age 40. Reducing screening frequency for those without a family history lowers program expenditures substantially at a modest loss of LYs. The results are sensitive to the CRC risk difference between positive and negative family histories.CONCLUSIONS:The cost-effectiveness of CRC FHS guidelines varies widely. Economic issues should be considered before implementing family history-directed screening programs.Am J Gastroenterol advance online publication, 11 May 2010; doi:10.1038/ajg.2010.185.

Response to the letter to the editor by Hassan et al.: The diminutive lesion versus the advanced adenoma: Which is the real target of CT colonography screening? (Article)

2009-09-01T00:00:00Z

Individualizing colonoscopy screening by sex and race (Article)

2009-07-01T00:00:00Z

Background: There is increasing discussion whether colorectal cancer (CRC) screening guidelines should be individualized by sex and race. Objectives: To determine individualized colonoscopic screening guidelines by sex and race for the average-risk population and to compare the cost-effectiveness of this approach with that of uniform guidelines for all. Design: We used the MISCAN-Colon microsimulation model to estimate life expectancy and lifetime CRC screening and treatment costs in a U.S. cohort of black and white men and women at average risk for CRC. We compared the base-case strategy of no screening and 3 competing colonoscopy strategies: (1) the currently recommended "uniform 10-yearly colonoscopy from age 50 years," (2) a shorter interval "uniform 8-yearly colonoscopy from age 51 years," and (3) "individualized screening according to sex and race.". Results: The base-case strategy of no screening was the least expensive, yet least effective. The uniform 10-yearly colonoscopy strategy was dominated. The uniform 8-yearly colonoscopy and individualized strategies both increased life expectancy by 0.0433 to 0.0435 years per individual, at a cost of $15,565 to $15,837 per life-year gained. In the individualized strategy, blacks began screening 6 years earlier, with a 1-year shorter interval compared with whites. The individualized policies were essentially the same for men and women, because the higher CRC risk in men was offset by their shorter life expectancy. The results were robust for changes in model assumptions. Conclusions: The improvements in costs and effects of individualizing CRC screening on a population level were only marginal. Individualized guidelines, however, could contribute to decreasing disparities between blacks and whites. The acceptability and feasibility of individualized guidelines, therefore, should be explored.

Screening for colorectal cancer: Random comparison of guaiac and immunochemical faecal occult blood testing at different cut-off levels (Article)

2009-04-07T00:00:00Z

Immunochemical faecal occult blood testing (FIT) provides quantitative test results, which allows optimisation of the cut-off value for follow-up colonoscopy. We conducted a randomised population-based trial to determine test characteristics of FIT (OC-Sensor micro, Eiken, Japan) screening at different cut-off levels and compare these with guaiac-based faecal occult blood test (gFOBT) screening in an average risk population. A representative sample of the Dutch population (n10 011), aged 50-74 years, was 1: 1 randomised before invitation to gFOBT and FIT screening. Colonoscopy was offered to screenees with a positive gFOBT or FIT (cut-off 50 ng haemoglobin/ml). When varying the cut-off level between 50 and 200 ng ml 1, the positivity rate of FIT ranged between 8.1% (95% CI: 7.2-9.1%) and 3.5% (95% CI: 2.9-4.2%), the detection rate of advanced neoplasia ranged between 3.2% (95% CI: 2.6-3.9%) and 2.1% (95% CI: 1.6-2.6%), and the specificity ranged between 95.5% (95% CI: 94.5-96.3%) and 98.8% (95% CI: 98.4-99.0%). At a cut-off value of 75 ng ml 1, the detection rate was two times higher than with gFOBT screening (gFOBT: 1.2%; FIT: 2.5%; P0.001), whereas the number needed to scope (NNscope) to find one screenee with advanced neoplasia was similar (2.2 vs 1.9; P0.69). Immunochemical faecal occult blood testing is considerably more effective than gFOBT screening within the range of tested cut-off values. From our experience, a cut-off value of 75 ng ml 1 provided an adequate positivity rate and an acceptable trade-off between detection rate and NNscope.

At what costs will screening with CT colonography be competitive? A cost-effectiveness approach (Article)

2009-03-01T00:00:00Z

The costs of computed tomographic colonography (CTC) are not yet established for screening use. In our study, we estimated the threshold costs for which CTC screening would be a cost-effective alternative to colonoscopy for colorectal cancer (CRC) screening in the general population. We used the MISCAN-colon microsi-mulation model to estimate the costs and life-years gained of screening persons aged 50-80 years for 4 screening strategies: (i) optical colonoscopy; and CTC with referral to optical colonoscopy of (ii) any suspected polyp; (iii) a suspected polyp ≥6 mm and (iv) a suspected polyp ≥ 10 mm. For each of the 4 strategies, screen intervals of 5, 10, 15 and 20 years were considered. Subsequently, for each CTC strategy and interval, the threshold costs of CTC were calculated. We performed a sensitivity analysis to assess the effect of uncertain model parameters on the threshold costs. With equal costs ($662), optical colonoscopy dominated CTC screening. For CTC to gain similar life-years as colonoscopy screening every 10 years, it should be offered every 5 years with referral of polyps ≥6 mm. For this strategy to be as cost-effective as colonoscopy screening, the costs must not exceed $285 or 43% of colonoscopy costs (range in sensitivity analysis: 39-47%). With 25% higher adherence than colonoscopy, CTC threshold costs could be 71% of colonoscopy costs. Our estimate of 43% is considerably lower than previous estimates in literature, because previous studies only compared CTC screening to 10-yearly colonoscopy, where we compared to different intervals of colonoscopy screening.