Optimizing Positivity Thresholds for a Risk-Adapted Screening Strategy in Colorectal Cancer Screening.

INTRODUCTION: Risk-adapted screening combining the Asia-Pacific Colorectal Screening score, fecal immunochemical test (FIT), and colonoscopy improved the yield of colorectal cancer screening than FIT. However, the optimal positivity thresholds of risk scoring and FIT of such a strategy warrant further investigation. METHODS: We included 3,407 participants aged 50-74 years undergoing colonoscopy from a colorectal cancer screening trial. For the risk-adapted screening strategy, subjects were referred for subsequent colonoscopy or FIT according to their risk scores. Diagnostic performance was evaluated for FIT and the risk-adapted screening method with various positivity thresholds. Furthermore, a modeled screening cohort was established to compare the yield and cost using colonoscopy, FIT, and the risk-adapted screening method in a single round of screening. RESULTS: Risk-adapted screening method had higher sensitivity for advanced neoplasm (AN) (27.6%-76.3% vs 13.8%-17.3%) but lower specificity (46.6%-90.8% vs 97.4%-98.8%) than FIT did. In a modeled screening cohort, FIT-based screening would be slightly affected because the threshold varied with a reduction of 76.0%-80.9% in AN detection and 82.0%-84.4% in cost when compared with colonoscopy. By contrast, adjusting the threshold of Asia-Pacific Colorectal Screening score from 3 to 5 points for risk-adapted screening varied from an increase of 12.6%-14.1% to a decrease of 55.6%-60.1% in AN detection, with the reduction of cost from 4.2%-5.3% rising to 66.4%-68.5%. DISCUSSION: With an appropriate positivity threshold tailored to clinical practice, the risk-adapted screening could save colonoscopy resources and cost compared with the colonoscopy-only and FIT-only strategies.

Efficacy and cost-effectiveness of fecal immunochemical test versus colonoscopy in colorectal cancer screening: a systematic review and meta-analysis.

BACKGROUND AND AIMS: The fecal immunochemical test (FIT) and colonoscopy are the most commonly used strategies for colorectal cancer (CRC) screening worldwide. We aimed to compare their efficacy and cost-effectiveness in CRC screening in an average-risk population. METHODS: PubMed, Embase, and National Health Services Economic Evaluation Database were searched. Risk ratio (RR) was used to evaluate the differences in detection rates of colorectal neoplasia between FIT and colonoscopy groups. A random-effects model was used to pool RRs. Incremental cost-effectiveness ratios (ICERs) were calculated to evaluate the cost-effectiveness of FIT versus colonoscopy. RESULTS: Six randomized controlled trials and 17 cost-effectiveness studies were included. The participation rate in the FIT group was higher than that in the colonoscopy group (41.6% vs 21.9%). In the intention-to-treat analysis, FIT had a detection rate of CRC comparable with colonoscopy (RR, .73; 95% confidence interval, .37-1.42) and lower detection rates of any adenoma and advanced adenoma than 1-time colonoscopy. Most included cost-effectiveness studies showed that annual (13/15) or biennial (5/6) FIT was cost-saving (ICER < $0) or very cost-effective ($0 < ICER ≤ $25000/quality-adjusted life-year) compared with colonoscopy every 10 years. CONCLUSIONS: FIT may be similar to 1-time colonoscopy in the detection rate of CRC, although it has lower detection rates of any adenoma and advanced adenoma than 1-time colonoscopy. Furthermore, annual or biennial FIT appears to be very cost-effective or cost-saving compared with colonoscopy every 10 years. These findings indicate, at least partly, that FIT is noninferior to colonoscopy in CRC screening in an average-risk population. Our findings should be treated with caution and need to be further confirmed.

Cost-Effectiveness and National Effects of Initiating Colorectal Cancer Screening for Average-Risk Persons at Age 45 Years Instead of 50 Years.

BACKGROUND & AIMS: The American Cancer Society has recommended initiating colorectal cancer (CRC) screening at age 45 years instead of 50 years. We estimated the cost effectiveness and national effects of adopting this recommendation. METHODS: We compared screening strategies and alternative resource allocations in a validated Markov model. We based national projections on screening participation rates by age and census data. RESULTS: Screening colonoscopy initiation at age 45 years instead of 50 years in 1000 persons averted 4 CRCs and 2 CRC deaths, gained 14 quality-adjusted life-years (QALYs), cost $33,900/QALY gained, and required 758 additional colonoscopies. These 758 colonoscopies could instead be used to screen 231 currently unscreened 55-year-old persons or 342 currently unscreened 65-year-old persons, through age 75 years. These alternatives averted 13-14 CRC cases and 6-7 CRC deaths and gained 27-28 discounted QALYs while saving $163,700-$445,800. Improving colonoscopy completion rates after abnormal results from a fecal immunochemical test yielded greater benefits and savings. Initiation of fecal immunochemical testing at age 45 years instead of 50 years cost $7700/QALY gained. Shifting current age-specific screening rates to 5 years earlier could avert 29,400 CRC cases and 11,100 CRC deaths over the next 5 years but would require 10.7 million additional colonoscopies and cost an incremental $10.4 billion. Improving screening rates to 80% in persons who are 50-75 years old would avert nearly 3-fold more CRC deaths at one third the incremental cost. CONCLUSIONS: In a Markov model analysis, we found that starting CRC screening at age 45 years is likely to be cost effective. However, greater benefit, at lower cost, could be achieved by increasing participation rates for unscreened older and higher-risk persons.

Faecal immunochemical tests versus colonoscopy for post-polypectomy surveillance: an accuracy, acceptability and economic study.

BACKGROUND: In the UK, patients with one or two adenomas, of which at least one is ≥ 10 mm in size, or three or four small adenomas, are deemed to be at intermediate risk of colorectal cancer (CRC) and referred for surveillance colonoscopy 3 years post polypectomy. However, colonoscopy is costly, can cause discomfort and carries a small risk of complications. OBJECTIVES: To determine whether or not annual faecal immunochemical tests (FITs) are effective, acceptable and cost saving compared with colonoscopy surveillance for detecting CRC and advanced adenomas (AAs). DESIGN: Diagnostic accuracy study with health psychology assessment and economic evaluation. SETTING: Participants were recruited from 30 January 2012 to 30 December 2013 within the Bowel Cancer Screening Programme in England. PARTICIPANTS: Men and women, aged 60-72 years, deemed to be at intermediate risk of CRC following adenoma removal after a positive guaiac faecal occult blood test were invited to participate. Invitees who consented and returned an analysable FIT were included. INTERVENTION: We offered participants quantitative FITs at 1, 2 and 3 years post polypectomy. Participants testing positive with any FIT were referred for colonoscopy and not offered further FITs. Participants testing negative were offered colonoscopy at 3 years post polypectomy. Acceptibility of FIT was assessed using discussion groups, questionnaires and interviews. MAIN OUTCOME MEASURES: The primary outcome was 3-year sensitivity of an annual FIT versus colonoscopy at 3 years for detecting advanced colorectal neoplasia (ACN) (CRC and/or AA). Secondary outcomes included participants' surveillance preferences, and the incremental costs and cost-effectiveness of FIT versus colonoscopy surveillance. RESULTS: Of 8008 invitees, 5946 (74.3%) consented and returned a round 1 FIT. FIT uptake in rounds 2 and 3 was 97.2% and 96.9%, respectively. With a threshold of 40 µg of haemoglobin (Hb)/g faeces (hereafter referred to as µg/g), positivity was 5.8% in round 1, declining to 4.1% in round 3. Over three rounds, 69.2% (18/26) of participants with CRC, 34.3% (152/443) with AAs and 35.6% (165/463) with ACN tested positive at 40 µg/g. Sensitivity for CRC and AAs increased, whereas specificity decreased, with lower thresholds and multiple rounds. At 40 µg/g, sensitivity and specificity of the first FIT for CRC were 30.8% and 93.9%, respectively. The programme sensitivity and specificity of three rounds at 10 µg/g were 84.6% and 70.8%, respectively. Participants' preferred surveillance strategy was 3-yearly colonoscopy plus annual FITs (57.9%), followed by annual FITs with colonoscopy in positive cases (31.5%). FIT with colonoscopy in positive cases was cheaper than 3-yearly colonoscopy (£2,633,382), varying from £485,236 (40 µg/g) to £956,602 (10 µg/g). Over 3 years, FIT surveillance could miss 291 AAs and eight CRCs using a threshold of 40 µg/g, or 189 AAs and four CRCs using a threshold of 10 µg/g. CONCLUSIONS: Annual low-threshold FIT with colonoscopy in positive cases achieved high sensitivity for CRC and would be cost saving compared with 3-yearly colonoscopy. However, at higher thresholds, this strategy could miss 15-30% of CRCs and 40-70% of AAs. Most participants preferred annual FITs plus 3-yearly colonoscopy. Further research is needed to define a clear role for FITs in surveillance. FUTURE WORK: Evaluate the impact of ACN missed by FITs on quality-adjusted life-years. TRIAL REGISTRATION: Current Controlled Trials ISRCTN18040196. FUNDING: National Institute for Health Research (NIHR) Health Technology Assessment programme, NIHR Imperial Biomedical Research Centre and the Bobby Moore Fund for Cancer Research UK. MAST Group Ltd provided FIT kits.

Cost-effectiveness of colorectal cancer screening programmes using sigmoidoscopy and immunochemical faecal occult blood test.

OBJECTIVE: Several European countries are implementing organized colorectal cancer (CRC) screening programmes using faecal immunochemical test (FIT) and/or flexible sigmoidoscopy (FS), but the cost-effectiveness of these programmes is not yet available. We aimed to assess cost-effectiveness, based on data from the established Piedmont screening programme. METHODS: Using the Piedmont programme data, a Markov model was constructed comparing three strategies in a simulated cohort of 100,000 subjects: single FS, biennial FIT, or sequential strategy (FS + FIT offered to FS non-responders). Estimates for CRC incidence and mortality prevention were derived from studies of organized screening. Cost analysis for FS and FIT was based on data from organized programmes. Incremental cost-effectiveness ratios (ICER) between the different strategies were calculated. Sensitivity and probabilistic analyses were performed. RESULTS: Direct costs for FS, and for FIT at first and subsequent rounds, were estimated as €160, €33, and €21, respectively. All the simulated strategies were effective (10-17% CRC incidence reduction) and cost-effective vs. no screening (ICER <€1000 per life-year saved). FS and FS + FIT were the only cost-saving strategies, with FS least expensive (€15 saving per person invited). FS + FIT and FS were the only non-dominated strategies. FS + FIT were more effective and cost-effective than FS (ICER €1217 per life-year saved). The residual marginal uncertainty was mainly related to parameters inherent to FIT effectiveness and adherence. CONCLUSIONS: Organized CRC screening programmes are highly cost-effective, irrespective of the test selected. A sequential approach with FS and FIT appears the most cost-effective option. A single FS is the least expensive, but convenient, approach.

[Evaluation of the capillary assay of C-reactive protein (CRP) through the lenght of consultation in pediatric emergencies and its economic impact]. / Évaluation du dosage capillaire de la protéine C-réactive (CRP) sur la durée de consultation aux urgences pédiatriques et impact économique.

Fever is a frequent reason for consultation in pediatric emergency departments and raises the question of biological and radiological examinations. Rapidly obtaining the result of C-reactive protein (CRP) level is essential in front of the steady increase of the number of visits. We carried out a prospective study within the pediatric emergency department of the University Hospital of Clermont-Ferrand from January to April 2017, in order to evaluate the interest of the capillary CRP in point of care (POCT). In two periods, 68 patients (28 controls without and 40 cases with capillary CRP assayed on a Afinion® AS100) with naked fever greater than 48 hours were included. After a study of the analytical performances of Afinion® and a verification of the homogeneity and the comparability of the two groups on clinical criteria (age, sex, duration of the fever, antibiotics treatment) and biological (values of CRP), the interest of the CRP in POCT was evaluated. In the POCT group, a significant drop in the median of the emergency room consultation time (60 (IQR 33-125) versus 180 (IQR 158-208) minutes), the number of biological acts by patient (1 (IQR 1-3) versus 7 (IQR 3-8)), the global cost of biological and radiological examinations per patient (5.4 (IQR 5.4-32.6) versus 153.8 (IQR 46.9-180.4) euros), and the cost of reagents spent by the laboratory per patient (5.2 (IQR 5.2-6.4) versus 33.2 (IQR 2.3-34.2) euros). Thus, in the context of a clinical-biological partnership, the use of CRP in POCT present a practical and an economic interest.

Cost Effectiveness of Screening Colonoscopy Depends on Adequate Bowel Preparation Rates - A Modeling Study.

BACKGROUND: Inadequate bowel preparation during screening colonoscopy necessitates repeating colonoscopy. Studies suggest inadequate bowel preparation rates of 20-60%. This increases the cost of colonoscopy for our society. AIM: The aim of this study is to determine the impact of inadequate bowel preparation rate on the cost effectiveness of colonoscopy compared to other screening strategies for colorectal cancer (CRC). METHODS: A microsimulation model of CRC screening strategies for the general population at average risk for CRC. The strategies include fecal immunochemistry test (FIT) every year, colonoscopy every ten years, sigmoidoscopy every five years, or stool DNA test every 3 years. The screening could be performed at private practice offices, outpatient hospitals, and ambulatory surgical centers. RESULTS: At the current assumed inadequate bowel preparation rate of 25%, the cost of colonoscopy as a screening strategy is above society's willingness to pay (<$50,000/QALY). Threshold analysis demonstrated that an inadequate bowel preparation rate of 13% or less is necessary before colonoscopy is considered more cost effective than FIT. At inadequate bowel preparation rates of 25%, colonoscopy is still more cost effective compared to sigmoidoscopy and stool DNA test. Sensitivity analysis of all inputs adjusted by ±10% showed incremental cost effectiveness ratio values were influenced most by the specificity, adherence, and sensitivity of FIT and colonoscopy. CONCLUSIONS: Screening colonoscopy is not a cost effective strategy when compared with fecal immunochemical test, as long as the inadequate bowel preparation rate is greater than 13%.

The cost-effectiveness of immunochemical tests for colorectal cancer screening.

BACKGROUND: The optimal immunochemical test to use for generalised mass screening is still under debate in France. AIM: To compare the cost and effectiveness in biennial screening for colorectal cancer of fifteen strategies consisting of the three-stool sample un-rehydrated guaiac faecal occult blood test and three immunochemical tests: Magstream, FOB-Gold and OC-Sensor, at different positivity cut-off levels and stool-sample collection. METHODS: A Markov model was used to compare these strategies in a general population of 100,000 individuals aged 50-74 over a 20-year period. RESULTS: Immunochemical tests were efficient strategies compared with guaiac faecal occult blood test. When all 15 strategies were compared with each other, only five of them remained efficient: the one- and two-stool sample Magstream, the one- and two-stool sample FOB-Gold with the 176 ng/mL cut-off, and the two-stool sample OC-Sensor with the 150 ng/mL cut-off. Sensitivity analyses showed that, at an identical price, the one-stool sample OC-Sensor was the most efficient strategy, and outperformed FOB-Gold. CONCLUSION: One-stool immunochemical testing can be considered a promising alternative to the guaiac faecal occult blood test for colorectal cancer mass screening in the general population. Competition between manufacturers should now be introduced to reduce purchase price differences.

A novel method for detection of apoptosis.

There are two different Angiotensin II (ANG II) peptides in nature: Human type (ANG II) and Bovine type (ANG II). These eight amino acid peptides differ only at position 5 where Valine is replaced by Isoleucine in the Bovine type. They are present in all species studied so far. These amino acids are different by only one atom of carbon. This difference is so small, that it will allow any of ANG II, Bovine or Human antibodies to interact with all species and create a universal method for apoptosis detection. ANG II concentrations are found at substantially higher levels in apoptotic, compared to non-apoptotic, tissues. ANG II accumulation can lead to DNA damage, mutations, carcinogenesis and cell death. We demonstrate that Bovine antiserum can be used for universal detection of apoptosis. In 2010, the worldwide market for apoptosis detection reached the $20 billion mark and significantly increases each year. Most commercially available methods are related to Annexin V and TUNNEL. Our new method based on ANG II is more widely known to physicians and scientists compared to previously used methods. Our approach offers a novel alternative for assessing apoptosis activity with enhanced sensitivity, at a lower cost and ease of use.

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 analysis of a quantitative immunochemical test for colorectal cancer screening.

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.

Cost-effectiveness analysis for determining optimal cut-off of immunochemical faecal occult blood test for population-based colorectal cancer screening (KCIS 16).

OBJECTIVES: We aimed to determine the optimal cut-off of the immunochemical faecal occult blood test (iFOBT) by using cost-effectiveness analysis. METHODS: A total of 22,672 subjects aged 50 years or older were invited to have an uptake of iFOBT. We collected data from screen-detected cases for the cut-off above 100 ng/mL and obtained interval cancers from a nationwide cancer registry for a cut-off below 100 ng/mL. We found a total of 65 colorectal cancer (CRC) cases, including 43 detected by screen and 22 diagnosed between screens (interval cases). The optimal cut-off was first determined by receiver operating characteristics (ROC) curve analysis. Formal economic evaluation was further applied to identifying the optimal cut-off by assessing the minimum incremental cost-effectiveness ratio (ICER), an indicator for cost per life year gained (effectiveness), given a series of cut-offs of iFOBT, ranging from 30 to 200 ng/mL compared with no screening. RESULTS: ROC curve analysis found the optimal cut-off of iFOBT to be 100 ng/mL at which the sensitivity, false-positive and odds of being affected given a positive result were 81.5% (70.2%-89.2%), 5.7% (5.4%-6.0%) and 1.24 (1.19-1.32), respectively. The area under ROC curve was 0.87 (0.81-0.93). In economic appraisal, the screening programme irrespective of any cut-off dominated (less cost and more effectiveness) over the control group. The optimal cut-off (the lowest ICER) was 110 ng/mL at which an average of 0.054 life year was gained and that of 950 ($US) was saved. CONCLUSIONS: We used cost-effectiveness to identify 110 ng/mL as the optimal cut-off of iFOBT in a Taiwanese population-based screening for CRC. Our model provides a useful approach for health policy-makers in designing population-based screening for CRC to determine the optimal cut-off of iFOBT when cost and effectiveness need to be taken into account.

Proposal for relative units of value (RUV) for use in allergy examinations.

Health resources are limited and consequently real cost generators must be identified to optimize resources. In the present article, we describe the structure of the Homogeneous Functional Groups (HFG) for Diagnostic Techniques in the Allergy Department of the Virgen de la Arrixaca University Hospital in Murcia (Spain) and the healthcare products generated. Based on the 2005 budget, variable costing was used to calculate the costs of the healthcare products generated (skin tests, investigation of drug allergies, etc.) by one of the three HFG (the HFG for complementary investigations). On the basis of these costs, and taking as the unit the cost of one skin prick test, we assigned relative units of value (RUV) to each of the products in our services portfolio. The following conclusions can be drawn: 1) the current system of variable costing provides information, which should be useful to health professionals; 2) the real cost generators in the microcosm of daily clinical practice should be identified to allow resource reallocation; 3) the costing system used enables modifications to be made that allow decision making on optimal use of the budget; 4) to take the decisions required to optimize resources, clinical management and complementary tests should go hand-in-hand.

A comparison of three stool tests for colorectal cancer screening.

The annual guaiac or immunochemical fecal occult blood test (FOBT) is one of the five colorectal cancer (CRC) screening regimens recommended by the American Cancer Society (Smith, Cokkinides, & Eyre, 2005). Stool-based deoxyribonucleic acid (DNA) testing for CRC is considered a promising technology (Smith, Cokkinides, & Eyre, 2003). Numerous features of three noninvasive stool tests for CRC are compared.

From guaiac to immune fecal occult blood tests: the emergence of technology in colorectal cancer screening.

Colorectal cancer is the second leading cause of cancer deaths in the United States for both men and women. Colorectal cancer screening is an important means for reducing morbidity and mortality. The American Cancer Society recommends five different screening regimens for adults of average risk, age 50 years and older. The optimal effectiveness of a screening program is dependent on the accuracy of the screening test used. An accurate screening test would have high sensitivity (positive) when an adenomatous polyp or cancer is present and high specificity (negative) in their absence. In April 2002, the American Cancer Society Colorectal Cancer Advisory Group concluded that the immunochemical fecal occult blood test has some advantages that merit revision of their guideline statement for fecal occult blood testing, to include the immunochemical fecal occult blood test. The advantages cited were the possibility of improved sensitivity and specificity and the lack of required dietary restrictions, which make it a more patient-friendly test. Several types of immunochemical fecal occult blood tests are discussed in this article, including their advantages and disadvantages compared with those of the traditional guaiac fecal occult blood testing.