Interval cancers in a national colorectal screening programme based on faecal immunochemical testing: Implications for faecal haemoglobin concentration threshold and sex inequality.

OBJECTIVE: To compare interval cancer proportions (ICP) in the faecal immunochemical test (FIT)-based Scottish Bowel Screening Programme (SBoSP) with the former guaiac faecal occult blood test (gFOBT)-based SBoSP and investigate associations between interval cancer (IC) and faecal haemoglobin concentration (f-Hb) threshold, sex, age, deprivation, site, and stage. METHODS: The ICP data from first year of the FIT-based SBoSP and the penultimate year of the gFOBT-based SBoSP were compared in a prospective cohort design. RESULTS: With FIT, 801 colorectal cancers (CRCs) were screen detected (SDC), 802 were in non-participants, 548 were ICs, 39 were colonoscopy missed and 72 were diagnosed after incomplete screening; with gFOBT: 540, 904, 556, 45, and 13, respectively. FIT had a significantly higher proportion of SDC compared to IC than gFOBT. For FIT and gFOBT, ICP was significantly higher in women than men. As f-Hb threshold increased, ICP increased and, for any f-Hb threshold for men, a lower threshold was required for comparable ICP in women. In Scotland, the current threshold of ≥80 µg Hb/g faeces would have to be lowered to ≥40 µg Hb/g faeces for women to achieve sex equality for ICP. In the FIT-based SBoSP, there were four times as many stage I SDC than IC. This was reversed in advanced stages, with twice as many stage IV CRC diagnosed as IC versus SDC. CONCLUSIONS: Reducing the numbers of IC requires lowering the f-Hb threshold. Using different f-Hb thresholds for women and men could eliminate the sex disparity, but with additional colonoscopy.

Stool DNA testing for early detection of colorectal cancer: systematic review using the HTA Core Model® for Rapid Relative Effectiveness Assessment.

Background: Stool DNA testing for early detection of colorectal cancer (CRC) is a non-invasive technology with the potential to supplement established CRC screening tests. The aim of this health technology assessment was to evaluate effectiveness and safety of currently CE-marked stool DNA tests, compared to other CRC tests in CRC screening strategies in an asymptomatic screening population. Methods: The assessment was carried out following the guidelines of the European Network for Health Technology Assessment (EUnetHTA). This included a systematic literature search in MED-LINE, Cochrane and EMBASE in 2018. Manufacturers were asked to provide additional data. Five patient interviews helped assessing potential ethical or social aspects and patients' experiences and preferences. We assessed the risk of bias using QUADAS-2, and the quality of the body of evidence using GRADE. Results: We identified three test accuracy studies, two of which investigated a multitarget stool DNA test (Cologuard®, compared fecal immunochemical test (FIT)) and one a combined DNA stool assay (ColoAlert®, compared to guaiac-based fecal occult blood test (gFOBT), Pyruvate Kinase Isoenzyme Type M2 (M2-PK) and combined gFOBT/M2-PK). We found five published surveys on patient satisfaction. No primary study investigating screening effects on CRC incidence or on overall mortality was found. Both stool DNA tests showed in direct comparison higher sensitivity for the detection of CRC and (advanced) adenoma compared to FIT, or gFOBT, respectively, but had lower specificity. However, these comparative results may depend on the exact type of FIT used. The reported test failure rates were higher for stool DNA testing than for FIT. The certainty of evidence was moderate to high for Cologuard® studies, and low to very low for the ColoAlert® study which refers to a former version of the product and yielded no direct evidence on the test accuracy for ad-vanced versus non-advanced adenoma. Conclusions: ColoAlert® is the only stool DNA test currently sold in Europe and is available at a lower price than Cologuard®, but reliable evidence is lacking. A screening study including the current product version of ColoAlert® and suitable comparators would, therefore, help evaluate the effectiveness of this screening option in a European context.

Healthcare costs, resource utilization, and productivity loss associated with colorectal cancer screening.

OBJECTIVES: To evaluate healthcare costs, resource utilization, associated costs, and lost productivity for colorectal cancer (CRC) screening in an average-risk population. METHODS: This retrospective cohort study identified average-risk individuals (50-75 years) with claims in the Optum Research Database for CRC screening test between 1 January 2014 to 31 December 2018. Index date was defined as the first date of a claim for colonoscopy, fecal immunochemical test (FIT), guaiac-based fecal occult blood test (FOBT) or multi-target stool DNA test (mt-sDNA). Screening costs were evaluated with descriptive statistics and multivariable analyses, adjusting for patient characteristics and index screening costs. RESULTS: In total, 903,831 individuals were identified by test groups: mt-sDNA (n = 29,614), FIT (n = 254,002), guaiac-based FOBT (n = 112,757) and colonoscopy (n = 507,458). Adjusted costs for index screening were, colonoscopy ($3,029), mt-sDNA ($752), FIT ($45), and (FOBT ($153). Adjusted costs across the six months following the index screening were $146 for colonoscopy, $329 for mt-sDNA, $306 for FIT, and $412 for FOBT. Colonoscopy had the highest costs for lost productivity. CONCLUSIONS: Screening colonoscopy had the highest productivity loss and healthcare costs up-front, suggesting potential cost benefits for noninvasive screening modalities. The more frequent screening interval required for FIT and FOBT resulted in a higher yearly cost than colonoscopy or mt-sDNA.

Colorectal cancer (CRC) is a prominent healthcare concern the United States, which accounted for 149,500 new cases and 52,980 deaths in 2021. Screening is effective for diagnosing the condition at earlier more treatable stages, and reducing deaths. However, screening is largely underutilized in part due to perceived cost barriers. This observational study used insurance claims data to calculate healthcare costs, resource use, and lost productivity for CRC screening in an average-risk population aged 50­75 years. A total of 903,831 individuals were identified by test groups: multi-target stool DNA test (mt-sDNA test; 29,614 individuals), fecal immunochemical test (FIT; 254,002 individuals), guaiac-based fecal occult blood test (FOBT; 112,757 individuals) and colonoscopy (507,458 individuals). Adjusted costs for initial screening were $3,029 for colonoscopy, $752 for mt-sDNA, $45 for FIT, and $153 for FOBT. Adjusted colonoscopy-related costs combined across the six months following the initial screening were $146 for the colonoscopy cohort, $329 for mt-sDNA, $306 for FIT, and $412 for FOBT. Colonoscopy had the highest costs for lost productivity. Overall, screening colonoscopy was accompanied by the highest productivity loss and up-front costs, suggesting potential cost benefits for noninvasive screening modalities ­ mt-sDNA, FIT, and FOBT; however, the more frequent screening interval required by FIT and FOBT resulted in a higher estimated average yearly screening cost.

Incident colorectal cancer screening and associated healthcare resource utilization and Medicare cost among Medicare beneficiaries aged 66-75 years in 2016-2018.

BACKGROUND: While prevalence of up-to-date screening status is the usual reported statistic, annual screening incidence may better reflect current clinical practices and is more actionable. Our main purpose was to examine incident colorectal cancer (CRC) screening rates in Medicare beneficiaries and to explore characteristics associated with CRC screening. METHODS: Using 20% Medicare random sample data, the study population included 2016-2018 Medicare fee-for-service beneficiaries covered by Parts A and B aged 66-75 years at average CRC risk. For each study year, we excluded individuals who had a Medicare claim for a colonoscopy within 9 years, flexible sigmoidoscopy within 4 years, and multitarget stool DNA test (mt-sDNA) within 2 years prior; therefore, any observed screening during study year was considered an "incident screening". Incident screening rates were calculated as number of incident screenings per 1000 Medicare beneficiaries. Overall rates were normalized to 2018 Medicare population distributions of age, sex, and race. RESULTS: Each year, > 1.4 million individuals met the inclusion/exclusion criteria from > 6.5 million Medicare beneficiaries. The overall adjusted incident CRC screening rate per 1000 Medicare beneficiaries increased from 85.2 in 2016 to 94.3 in 2018. Incident screening rates decreased 11.4% (22.9 to 20.3) for colonoscopy and 2.4% (58.3 to 56.9) for fecal immunochemical test/guaiac-based fecal occult blood test; they increased 201.5% (6.5 to 19.6) for mt-sDNA. The 2018 unadjusted rate was 76.0 for men and 110.4 for women. By race/ethnicity, the highest 2018 rate was for Asian individuals and the lowest rate was for Black individuals (113.4 and 72.8, respectively). CONCLUSIONS: The 2016-2018 observed incident CRC screening rate in average-risk Medicare beneficiaries, while increasing, was still low. Our findings suggest more work is needed to improve CRC screening overall and, especially, among male and Black Medicare beneficiaries.

Optimizing the Design of a Repeated Fecal Immunochemical Test Bowel Cancer Screening Programme With a Limited Endoscopy Capacity From a Health Economic Perspective.

OBJECTIVES: In 2016, it was announced that the fecal immunochemical test (FIT) would replace the guaiac fecal occult blood test in the UK Bowel Cancer Screening Programme. England has limited endoscopy capacity. This study informed decision making by determining the most cost-effective FIT screening strategy (age range, frequency, and FIT threshold) under a constrained endoscopy capacity. METHODS: An economic model with a colorectal cancer natural history component was used to model 60 221 screening strategies with first screening at age 50 to 60 years, screening interval of 1 to 6 years, 3+ screening episodes, and FIT integer threshold of 20 to 180 µg hemoglobin/g feces. Screening strategies requiring the same endoscopy capacity were compared to determine the characteristics of the most cost-effective strategies. RESULTS: With 50 000 annual screening referral colonoscopies, the 20 most cost-effective strategies had a starting age of 50 to 53 years, 2-yearly screening, 7 or 8 rounds of screening, and FIT threshold of 127 to 166. Compared with a 2-yearly screening interval, screening less frequently (3-, 4-, 5-, or 6-yearly) with a more sensitive FIT was less cost-effective. CONCLUSIONS: The UK Bowel Cancer Screening Programme should use a 2-yearly FIT screening interval. When endoscopy capacity increases, the screening starting age should be reduced first followed by reducing the FIT threshold. These findings are relevant for other colorectal cancer screening programs with constrained endoscopy capacity.

Utility of fecal immunochemical test vs guaiac fecal occult blood test for assessment of gastrointestinal bleed in hospitalized patients.

BACKGROUND: Guaiac fecal occult blood testing (gFOBT) is often used "off-label" for gastrointestinal (GI) bleeding. Fecal Immunochemical Test (FIT) is increasingly replacing gFOBT in colorectal cancer screening and may play a role in assessment for significant bowel disease. We examined the concordance of FIT with gFOBT (Hemoccult Sensa II) among inpatients and between day 1 and day 3 gFOBT results. METHODS: FIT was performed alongside gFOBT on all inpatient stool sent for occult blood to the Winnipeg Health Sciences Centre laboratory over 1 y. gFOBT was performed on days 1 and 3 post stool collection, while FIT was performed on day 1 only. RESULTS: Positivity rates were highest for Day 1 gFOBT (27.7%), and lowest for FIT (18.3%). Concordance between FIT and Days 1 and 3 gFOBT for negative test results (96.4% and 94.1%) was significantly higher than that expected by chance alone (58.7% and 61.3%, P < .001). Similarly, concordance for positive test results (55.8% and 55.6%) was significantly higher as well as for days 1 and 3 gFOBT results. CONCLUSIONS: We found no benefit in delayed testing for 3 days post collection. FIT provides equivalent results to gFOBT in hospitalized patients.

Effectiveness, benefit harm and cost effectiveness of colorectal cancer screening in Austria.

BACKGROUND: Clear evidence on the benefit-harm balance and cost effectiveness of population-based screening for colorectal cancer (CRC) is missing. We aim to systematically evaluate the long-term effectiveness, harms and cost effectiveness of different organized CRC screening strategies in Austria. METHODS: A decision-analytic cohort simulation model for colorectal adenoma and cancer with a lifelong time horizon was developed, calibrated to the Austrian epidemiological setting and validated against observed data. We compared four strategies: 1) No Screening, 2) FIT: annual immunochemical fecal occult blood test age 40-75 years, 3) gFOBT: annual guaiac-based fecal occult blood test age 40-75 years, and 4) COL: 10-yearly colonoscopy age 50-70 years. Predicted outcomes included: benefits expressed as life-years gained [LYG], CRC-related deaths avoided and CRC cases avoided; harms as additional complications due to colonoscopy (physical harm) and positive test results (psychological harm); and lifetime costs. Tradeoffs were expressed as incremental harm-benefit ratios (IHBR, incremental positive test results per LYG) and incremental cost-effectiveness ratios [ICER]. The perspective of the Austrian public health care system was adopted. Comprehensive sensitivity analyses were performed to assess uncertainty. RESULTS: The most effective strategies were FIT and COL. gFOBT was less effective and more costly than FIT. Moving from COL to FIT results in an incremental unintended psychological harm of 16 additional positive test results to gain one life-year. COL was cost saving compared to No Screening. Moving from COL to FIT has an ICER of 15,000 EUR per LYG. CONCLUSIONS: Organized CRC-screening with annual FIT or 10-yearly colonoscopy is most effective. The choice between these two options depends on the individual preferences and benefit-harm tradeoffs of screening candidates.

Cost-effectiveness of the faecal immunochemical test at a range of positivity thresholds compared with the guaiac faecal occult blood test in the NHS Bowel Cancer Screening Programme in England.

OBJECTIVES: Through the National Health Service (NHS) Bowel Cancer Screening Programme (BCSP), men and women in England aged between 60 and 74 years are invited for colorectal cancer (CRC) screening every 2 years using the guaiac faecal occult blood test (gFOBT). The aim of this analysis was to estimate the cost-utility of the faecal immunochemical test for haemoglobin (FIT) compared with gFOBT for a cohort beginning screening aged 60 years at a range of FIT positivity thresholds. DESIGN: We constructed a cohort-based Markov state transition model of CRC disease progression and screening. Screening uptake, detection, adverse event, mortality and cost data were taken from BCSP data and national sources, including a recent large pilot study of FIT screening in the BCSP. RESULTS: Our results suggest that FIT is cost-effective compared with gFOBT at all thresholds, resulting in cost savings and quality-adjusted life years (QALYs) gained over a lifetime time horizon. FIT was cost-saving (p<0.001) and resulted in QALY gains of 0.014 (95% CI 0.012 to 0.017) at the base case threshold of 180 µg Hb/g faeces. Greater health gains and cost savings were achieved as the FIT threshold was decreased due to savings in cancer management costs. However, at lower thresholds, FIT was also associated with more colonoscopies (increasing from 32 additional colonoscopies per 1000 people invited for screening for FIT 180 µg Hb/g faeces to 421 additional colonoscopies per 1000 people invited for screening for FIT 20 µg Hb/g faeces over a 40-year time horizon). Parameter uncertainty had limited impact on the conclusions. CONCLUSIONS: This is the first published economic analysis of FIT screening in England using data directly comparing FIT with gFOBT in the NHS BSCP. These results for a cohort starting screening aged 60 years suggest that FIT is highly cost-effective at all thresholds considered. Further modelling is needed to estimate economic outcomes for screening across all age cohorts simultaneously.

Harms, benefits and costs of fecal immunochemical testing versus guaiac fecal occult blood testing for colorectal cancer screening.

BACKGROUND: The ColonCancerCheck screening program for colorectal cancer (CRC) in Ontario, Canada, is considering switching from biennial guaiac fecal occult blood test (gFOBT) screening between age 50-74 years to the more sensitive, but also less specific fecal immunochemical test (FIT). The aim of this study is to estimate whether the additional benefits of FIT screening compared to gFOBT outweigh the additional costs and harms. METHODS: We used microsimulation modeling to estimate quality adjusted life years (QALYs) gained and costs of gFOBT and FIT, compared to no screening, in a cohort of screening participants. We compared strategies with various age ranges, screening intervals, and cut-off levels for FIT. Cost-efficient strategies were determined for various levels of available colonoscopy capacity. RESULTS: Compared to no screening, biennial gFOBT screening between age 50-74 years provided 20 QALYs at a cost of CAN$200,900 per 1,000 participants, and required 17 colonoscopies per 1,000 participants per year. FIT screening was more effective and less costly. For the same level of colonoscopy requirement, biennial FIT (with a high cut-off level of 200 ng Hb/ml) between age 50-74 years provided 11 extra QALYs gained while saving CAN$333,300 per 1000 participants, compared to gFOBT. Without restrictions in colonoscopy capacity, FIT (with a low cut-off level of 50 ng Hb/ml) every year between age 45-80 years was the most cost-effective strategy providing 27 extra QALYs gained per 1000 participants, while saving CAN$448,300. INTERPRETATION: Compared to gFOBT screening, switching to FIT at a high cut-off level could increase the health benefits of a CRC screening program without considerably increasing colonoscopy demand.

Cost-effectiveness simulation and analysis of colorectal cancer screening in Hong Kong Chinese population: comparison amongst colonoscopy, guaiac and immunologic fecal occult blood testing.

BACKGROUND: The aim of this study was to evaluate the cost-effectiveness of CRC screening strategies from the healthcare service provider perspective based on Chinese population. METHODS: A Markov model was constructed to compare the cost-effectiveness of recommended screening strategies including annual/biennial guaiac fecal occult blood testing (G-FOBT), annual/biennial immunologic FOBT (I-FOBT), and colonoscopy every 10 years in Chinese aged 50 year over a 25-year period. External validity of model was tested against data retrieved from published randomized controlled trials of G-FOBT. Recourse use data collected from Chinese subjects among staging of colorectal neoplasm were combined with published unit cost data ($USD in 2009 price values) to estimate a stage-specific cost per patient. Quality-adjusted life-years (QALYs) were quantified based on the stage duration and SF-6D preference-based value of each stage. The cost-effectiveness outcome was the incremental cost-effectiveness ratio (ICER) represented by costs per life-years (LY) and costs per QALYs gained. RESULTS: In base-case scenario, the non-dominated strategies were annual and biennial I-FOBT. Compared with no screening, the ICER presented $20,542/LYs and $3155/QALYs gained for annual I-FOBT, and $19,838/LYs gained and $2976/QALYs gained for biennial I-FOBT. The optimal screening strategy was annual I-FOBT that attained the highest ICER at the threshold of $50,000 per LYs or QALYs gained. CONCLUSION: The Markov model informed the health policymakers that I-FOBT every year may be the most effective and cost-effective CRC screening strategy among recommended screening strategies, depending on the willingness-to-pay of mass screening for Chinese population. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02038283.

Guaiac faecal occult blood test performance at initial and repeat screens in the English Bowel Cancer Screening Programme.

BACKGROUND: In many countries, screening for colorectal cancer (CRC) relies on repeat testing using the guaiac faecal occult blood test (gFOBT). This study aimed to compare gFOBT performance measures between initial and repeat screens. METHODS: Data on screening uptake and outcomes from the English Bowel Cancer Screening Programme (BCSP) for the years 2008 and 2011 were used. An existing CRC natural history model was used to estimate gFOBT sensitivity and specificity, and the cost-effectiveness of different screening strategies. RESULTS: The gFOBT sensitivity for CRC was estimated to decrease from 27.35% at the initial screen to 20.22% at the repeat screen. Decreases were also observed for the positive predictive value (8.4-7.2%) and detection rate for CRC (0.19-0.14%). Assuming equal performance measures for both the initial and repeat screens led to an overestimate of the cost effectiveness of gFOBT screening compared with the other screening modalities. CONCLUSIONS: Performance measures for gFOBT screening were generally lower in the repeat screen compared with the initial screen. Screening for CRC using gFOBT is likely to be cost-effective; however, the use of different screening modalities may result in additional benefits. Future economic evaluations of gFOBT should not assume equal sensitivities between screening rounds.

Mild alkali-pretreatment effectively extracts guaiacyl-rich lignin for high lignocellulose digestibility coupled with largely diminishing yeast fermentation inhibitors in Miscanthus.

In this study, various alkali-pretreated lignocellulose enzymatic hydrolyses were evaluated by using three standard pairs of Miscanthus accessions that showed three distinct monolignol (G, S, H) compositions. Mfl26 samples with elevated G-levels exhibited significantly increased hexose yields of up to 1.61-fold compared to paired samples derived from enzymatic hydrolysis, whereas Msa29 samples with high H-levels displayed increased hexose yields of only up to 1.32-fold. In contrast, Mfl30 samples with elevated S-levels showed reduced hexose yields compared to the paired sample of 0.89-0.98 folds at p<0.01. Notably, only the G-rich biomass samples exhibited complete enzymatic hydrolysis under 4% NaOH pretreatment. Furthermore, the G-rich samples showed more effective extraction of lignin-hemicellulose complexes than the S- and H-rich samples upon NaOH pretreatment, resulting in large removal of lignin inhibitors to yeast fermentation. Therefore, this study proposes an optimal approach for minor genetic lignin modification towards cost-effective biomass process in Miscanthus.

Nursing assessment of guaiac-positive and occult blood in preterm infant stools.

Guaiac testing the stool of very low birth weight (VLBW; <1,500 g) preterm infants has been a standard of care for many neonatal intensive care units (NICUs) and considered a diagnostic tool that could potentially provide early warning of gastrointestinal disturbances, feeding intolerance (FI), or necrotizing enterocolitis (NEC). Evidence to either support or eliminate testing stool for occult blood from standard care practices is lacking. Support to eliminate testing is often based on the knowledge that neonatal treatment interventions-such as gastric tube placement, intubation, and/or suctioning- may often result in occult blood in stools. However, there is also reasonable concern that occult blood may indicate a cascade of pathophysiological events, which may lead to FI and NEC, is in progress.Feeding intolerance remains one of the most consistent reasons VLBW preterm infants experience poor weight gain and extended hospital stays. Every nursing assessment is strategic to the early identification of contributing factors to either the development of FI or NEC. Including low-cost, noninvasive diagnostic tools to augment the findings of the nursing assessment can only help guide health care providers in appropriate decision making related to the feeding plan.

The economic evaluation of screening for colorectal cancer: Case of Iran.

BACKGROUND: Given increasing rates of colorectal cancer (CRC) in countries with intermediate incidence rates, the decision to implement population-based screening must consider the trade-off between high costs and a relatively low yield. We estimated the incremental cost-effectiveness ratio of 10 strategies for colorectal cancer screening, as well as no screening, incorporating quality of life, noncompliance, and data on the costs and benefits of chemotherapy in Iran. METHODS: We used a Markov model to measure the costs and quality-adjusted life expectancy of 50-year-old average-risk Iranian without screening and with screening by each test. In this study, we populated the model with data from the ministry of health and published literature. We considered costs from the perspective of a health insurance organization, with inflation to the 2011 Iranian Rial converted to US dollars. We focused on three tests of the 10 strategies considered, currently being used for population screening in some Iranian provinces (Mazandaran Kerman, Golestan, Ardabil, and Tehran): low-sensitivity guaiac fecal occult blood test, performed annually; fecal immunochemical test, performed annually; and colonoscopy, performed every 10 years. RESULTS: These strategies reduced the incidence of colorectal cancer by 39%, 60%, and 76% and mortality by 50%, 69%, and 78%, respectively, compared with no screening. These strategies generated ICER (incremental cost-effectiveness ratios) of $9067, $654, and $8700 per QALY (quality-adjusted life year), respectively. Sensitivity analyses were performed to evaluate the influence of various parameters on the cost-effectiveness of screening. The results were robust to probabilistic sensitivity analysis. Colonoscopy every 10 years yielded the greatest net health benefit. CONCLUSIONS: Screening for colorectal cancer is cost-effective over conventional levels of WTP (Willingness to Pay). Annual high-sensitivity fecal occult blood testing, such as a fecal immunochemical test, or colonoscopy every 10 years offer the best value for the money in Iran.

Screening for colorectal cancer with immunochemical faecal occult blood tests.

Population-based studies have shown that guaiac faecal occult blood testing followed by colonoscopy in case of positivity can reduce colorectal cancer mortality. However these tests have been criticised for their fairly low sensitivity. For this reason attention has been given to alternative tests. The aim of this paper is to review the evidence for screening for colorectal cancer using qualitative immunochemical faecal occult blood tests. For the complete range of tested cut-off values, immunochemical faecal occult blood tests lead to higher diagnostic yield, improved sensitivity and greater participation. The optimal number of samples and the optimal cut-off value has to suit local resources and the acceptability of missed cancers. All economic evaluations, despite some differences between studies, add further arguments to support the opinion that the immunochemical faecal occult blood test is currently the most cost-effective screening test for average-risk populations. These economic evaluations provide strong arguments in favour of the 1-sample strategy. With decreasing the cut-off value similar performances can be achieved with one-compared to two day sampling. Too few data are currently available to accurately compare existing qualitative tests.

Cost-effectiveness of population-based screening for colorectal cancer: a comparison of guaiac-based faecal occult blood testing, faecal immunochemical testing and flexible sigmoidoscopy.

BACKGROUND: Several colorectal cancer-screening tests are available, but it is uncertain which provides the best balance of risks and benefits within a screening programme. We evaluated cost-effectiveness of a population-based screening programme in Ireland based on (i) biennial guaiac-based faecal occult blood testing (gFOBT) at ages 55-74, with reflex faecal immunochemical testing (FIT); (ii) biennial FIT at ages 55-74; and (iii) once-only flexible sigmoidoscopy (FSIG) at age 60. METHODS: A state-transition model was used to estimate costs and outcomes for each screening scenario vs no screening. A third party payer perspective was adopted. Probabilistic sensitivity analyses were undertaken. RESULTS: All scenarios would be considered highly cost-effective compared with no screening. The lowest incremental cost-effectiveness ratio (ICER vs no screening euro 589 per quality-adjusted life-year (QALY) gained) was found for FSIG, followed by FIT euro 1696) and gFOBT (euro 4428); gFOBT was dominated. Compared with FSIG, FIT was associated with greater gains in QALYs and reductions in lifetime cancer incidence and mortality, but was more costly, required considerably more colonoscopies and resulted in more complications. Results were robust to variations in parameter estimates. CONCLUSION: Population-based screening based on FIT is expected to result in greater health gains than a policy of gFOBT (with reflex FIT) or once-only FSIG, but would require significantly more colonoscopy resources and result in more individuals experiencing adverse effects. Weighing these advantages and disadvantages presents a considerable challenge to policy makers.

Fecal occult blood testing when colonoscopy capacity is limited.

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 of mass screening for colorectal cancer: choice of fecal occult blood test and screening strategy.

BACKGROUND: Colorectal cancer is a major cause of mortality. This gives high public health priority to mass screening using a noninvasive, fecal occult blood test of asymptomatic individuals. A positive test selects those who should undergo colonoscopy to ensure early detection of colorectal cancer. Guaiac fecal occult blood test has low sensitivity. Automated immunochemical tests that measure the fecal human hemoglobin concentration are more sensitive and can be simplified as a 1- to 3-sample format with optimum cutoff points. OBJECTIVE: The aim was to improve the sensitivity of the test by choosing an accurate format (1- to 3-sample and optimum hemoglobin concentration) while maintaining acceptable specificity and avoiding alteration of the screening program in terms of quality of life and economic outputs. METHODS: We used a Markov model to estimate the cost-effectiveness of a screening program for a population of 100,000 asymptomatic individuals by use of immunological fecal tests with different cutoffs, leading to different sensitivity/specificity ratios, and to compare its incremental cost-effectiveness ratio compared with the guaiac fecal test program. RESULTS: The results suggest that a 3-sample immunological test with 50 ng/mL as a positive cutoff is cost-effective. It provides more asymptomatic cancer detection without significantly increasing normal colonoscopies. CONCLUSION: This format should be prospectively evaluated in mass screening.

Colorectal cancer screening comparing no screening, immunochemical and guaiac fecal occult blood tests: a cost-effectiveness analysis.

Comparability of cost-effectiveness of colorectal cancer (CRC) screening strategies is limited if heterogeneous study data are combined. We analyzed prospective empirical data from a randomized-controlled trial to compare cost-effectiveness of screening with either one round of immunochemical fecal occult blood testing (I-FOBT; OC-Sensor®), one round of guaiac FOBT (G-FOBT; Hemoccult-II®) or no screening in Dutch aged 50 to 75 years, completed with cancer registry and literature data, from a third-party payer perspective in a Markov model with first- and second-order Monte Carlo simulation. Costs were measured in Euros (€), effects in life-years gained, and both were discounted with 3%. Uncertainty surrounding important parameters was analyzed. I-FOBT dominated the alternatives: after one round of I-FOBT screening, a hypothetical person would on average gain 0.003 life-years and save the health care system €27 compared with G-FOBT and 0.003 life years and €72 compared with no screening. Overall, in 4,460,265 Dutch aged 50-75 years, after one round I-FOBT screening, 13,400 life-years and €320 million would have been saved compared with no screening. I-FOBT also dominated in sensitivity analyses, varying uncertainty surrounding important effect and cost parameters. CRC screening with I-FOBT dominated G-FOBT and no screening with or without accounting for uncertainty.