Cost-Effectiveness of Risk-Stratified Colorectal Cancer Screening Based on Polygenic Risk: Current Status and Future Potential.

BACKGROUND: Although uniform colonoscopy screening reduces colorectal cancer (CRC) mortality, risk-based screening may be more efficient. We investigated whether CRC screening based on polygenic risk is a cost-effective alternative to current uniform screening, and if not, under what conditions it would be. METHODS: The MISCAN-Colon model was used to simulate a hypothetical cohort of US 40-year-olds. Uniform screening was modeled as colonoscopy screening at ages 50, 60, and 70 years. For risk-stratified screening, individuals underwent polygenic testing with current and potential future discriminatory performance (area under the receiver-operating curve [AUC] of 0.60 and 0.65-0.80, respectively). Polygenic testing results were used to create risk groups, for which colonoscopy screening was optimized by varying the start age (40-60 years), end age (70-85 years), and interval (1-20 years). RESULTS: With current discriminatory performance, optimal screening ranged from once-only colonoscopy at age 60 years for the lowest-risk group to six colonoscopies at ages 40-80 years for the highest-risk group. While maintaining the same health benefits, risk-stratified screening increased costs by $59 per person. Risk-stratified screening could become cost-effective if the AUC value would increase beyond 0.65, the price per polygenic test would drop to less than $141, or risk-stratified screening would lead to a 5% increase in screening participation. CONCLUSIONS: Currently, CRC screening based on polygenic risk is unlikely to be cost-effective compared with uniform screening. This is expected to change with a greater than 0.05 increase in AUC value, a greater than 30% reduction in polygenic testing costs, or a greater than 5% increase in adherence with screening.

Colorectal Cancer: Cost-effectiveness of Colonoscopy versus CT Colonography Screening with Participation Rates and Costs.

Purpose To compare the cost-effectiveness of computed tomographic (CT) colonography and colonoscopy screening by using data on unit costs and participation rates from a randomized controlled screening trial in a dedicated screening setting. Materials and Methods Observed participation rates and screening costs from the Colonoscopy or Colonography for Screening, or COCOS, trial were used in a microsimulation model to estimate costs and quality-adjusted life-years (QALYs) gained with colonoscopy and CT colonography screening. For both tests, the authors determined optimal age range and screening interval combinations assuming a 100% participation rate. Assuming observed participation for these combinations, the cost-effectiveness of both tests was compared. Extracolonic findings were not included because long-term follow-up data are lacking. Results The participation rates for colonoscopy and CT colonography were 21.5% (1276 of 5924 invitees) and 33.6% (982 of 2920 invitees), respectively. Colonoscopy was more cost-effective in the screening strategies with one or two lifetime screenings, whereas CT colonography was more cost-effective in strategies with more lifetime screenings. CT colonography was the preferred test for willingness-to-pay-thresholds of €3200 per QALY gained and higher, which is lower than the Dutch willingness-to-pay threshold of €20 000. With equal participation, colonoscopy was the preferred test independent of willingness-to-pay thresholds. The findings were robust for most of the sensitivity analyses, except with regard to relative screening costs and subsequent participation. Conclusion Because of the higher participation rates, CT colonography screening for colorectal cancer is more cost-effective than colonoscopy screening. The implementation of CT colonography screening requires previous satisfactory resolution to the question as to how best to deal with extracolonic findings. © RSNA, 2018 Online supplemental material is available for this article.

Quality of life assumptions determine which cervical cancer screening strategies are cost-effective.

Quality-adjusted life years are used in cost-effectiveness analyses (CEAs). To calculate QALYs, a "utility" (0-1) is used for each health state induced or prevented by the intervention. We aimed to estimate the impact of quality of life (QoL) assumptions (utilities and durations of health states) on CEAs of cervical cancer screening. To do so, 12 alternative sets of utility assumptions were retrieved from published cervical cancer screening CEAs. Two additional sets were based on empirical QoL data that were integrally obtained through two different measures (SF-6D and EQ-5D) from eight groups of women (total n = 3,087), from invitation for screening to diagnosis with cervical cancer. Per utility set we calculated the number of quality-adjusted days lost (QADL) for each relevant health state in cervical cancer screening, by multiplying the study-specific assumed disutilities (i.e., 1-utility) with study-specific durations of the loss in QoL, resulting in 14 "QADL-sets." With microsimulation model MISCAN we calculated cost-effectiveness of 342 alternative screening programs (varying in primary screening test [Human Papillomavirus (HPV) vs. cytology], starting ages, and screening interval) for each of the 14 QADL-sets. Utilities used in CEAs appeared to differ largely. We found that ten QADL-sets from the literature resulted in HPV and two in cytology as preferred primary test. The SF-6D empirical QADL-set resulted in cytology and the EQ-5D one in HPV as preferred primary test. In conclusion, assumed utilities and health state durations determine cost-effectiveness of cervical cancer screening. Also, the measure used to empirically assess utilities can be crucial for CEA conclusions.

Cost-effectiveness of High-performance Biomarker Tests vs Fecal Immunochemical Test for Noninvasive Colorectal Cancer Screening.

BACKGROUND & AIMS: Biomarker assays could increase the accuracy of noninvasive detection of colorectal cancer (CRC); fecal immunochemical tests (FITs) are estimated to miss 27%-47% of CRCs and 70%-80% of advanced adenomas per round of screening. We investigated the conditions under which biomarker screens would be cost-effective compared with FIT screens of average-risk individuals. METHODS: We used the MISCAN-Colon microsimulation model to estimate the effects of various CRC screening test characteristics on life-years gained (LYG) and; age-specific all-cause mortality was based on the 2010 Dutch life tables. Simulated CRC incidence rate and CRC stage distribution were calibrated to observed data in The Netherlands from 1999 through 2003 (before opportunities for screening). Survival rates after diagnosis of CRC at an age younger than 75 years were based on CRC relative survival data from 1985 through 2004; survival for individuals diagnosed at an age of 75 years or older was adjusted to fit the observed age-increasing mortality/incidence ratio. We modeled FIT along with hypothetical biomarker tests with different test performance levels. For each biomarker test we calculated the maximum unit cost for the test to be cost-effective compared with FIT, assuming a willingness-to-pay threshold of €50,000 ($56,000) per LYG. RESULTS: Biennial FIT screening of subjects 55-75 years old provided 84.9 LYG at a cost of €122,000 ($137,000) per 1000 participants. Considering a unit cost of €7 ($8) for FIT (including kit and analysis only, excluding organizational costs), a biomarker test that detects CRC with higher levels of specificity and sensitivity (100%) and advanced adenomas at a proportionally higher level of sensitivity (53%) should never exceed a cost of €51 ($57). The threshold cost could increase to more than €200 ($224) for high-performing biomarker tests in cases of limited colonoscopy capacity or higher uptake of this test. CONCLUSIONS: By using the MISCAN-Colon microsimulation model to estimate effects of CRC screening tests, we found that for a biomarker test with increased overall performance to be cost-effective, it should not exceed 7-fold the unit cost of FIT. This maximum would increase substantially if colonoscopy becomes more expensive or scarce, or if the new test has higher screening uptake. These values could be used to estimate the added value of new biomarkers compared with current FIT screening.

Cost Effectiveness of Age-Specific Screening Intervals for People With Family Histories of Colorectal Cancer.

BACKGROUND & AIMS: Relative risk of colorectal cancer (CRC) decreases with age among individuals with a family history of CRC. However, no screening recommendations specify less frequent screening with increasing age. We aimed to determine whether such a refinement would be cost effective. METHODS: We determined the relative risk for CRC for individuals based on age and number of affected first-degree relatives (FDRs) using data from publications. For each number of affected FDRs, we used the Microsimulation Screening Analysis model to estimate costs and effects of colonoscopy screening strategies with different age ranges and intervals. Screening was then optimized sequentially, starting with the youngest age group, and allowing the interval of screening to change at certain ages. Strategies with an incremental cost effectiveness ratio below $100,000 per quality-adjusted life year were considered cost effective. RESULTS: For people with 1 affected FDR (92% of those with a family history), screening every 3 years beginning at an age of 40 years is most cost effective. If no adenomas are found, the screening interval can gradually be extended to 5 and 7 years, at ages 45 and 55 years, respectively. From a cost-effectiveness perspective, individuals with more affected FDRs should start screening earlier and at shorter intervals. However, frequency can be reduced if no abnormalities are found. CONCLUSIONS: Using a microsimulation model, we found that for individuals with a family history of CRC, it is cost effective to gradually increase the screening interval if several subsequent screening colonoscopies have negative results and no new cases of CRC are found in family members.

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.

Cervical Cancer Screening in Partly HPV Vaccinated Cohorts - A Cost-Effectiveness Analysis.

BACKGROUND: Vaccination against the oncogenic human papillomavirus (HPV) types 16 and 18 will reduce the prevalence of these types, thereby also reducing cervical cancer risk in unvaccinated women. This (measurable) herd effect will be limited at first, but is expected to increase over time. At a certain herd immunity level, tailoring screening to vaccination status may no longer be worth the additional effort. Moreover, uniform screening may be the only viable option. We therefore investigated at what level of herd immunity it is cost-effective to also reduce screening intensity in unvaccinated women. METHODS: We used the MISCAN-Cervix model to determine the optimal screening strategy for a pre-vaccination population and for vaccinated women (~80% decreased risk), assuming a willingness-to-pay of €50,000 per quality-adjusted life year gained. We considered HPV testing, cytology testing and co-testing and varied the start age of screening, the screening interval and the number of lifetime screens. We then calculated the incremental cost-effectiveness ratio (ICER) of screening unvaccinated women with the strategy optimized to the pre-vaccination population as compared to with the strategy optimized to vaccinated women, assuming different herd immunity levels. RESULTS: Primary HPV screening with cytology triage was the optimal strategy, with 8 lifetime screens for the pre-vaccination population and 3 for vaccinated women. The ICER of screening unvaccinated women 8 times instead of 3 was €28,085 in the absence of herd immunity. At around 50% herd immunity, the ICER reached €50,000. CONCLUSION: From a herd immunity level of 50% onwards, screening intensity based on the pre-vaccination risk level becomes cost-ineffective for unvaccinated women. Reducing the screening intensity of uniform screening may then be considered.

Personalizing colonoscopy screening for elderly individuals based on screening history, cancer risk, and comorbidity status could increase cost effectiveness.

BACKGROUND & AIMS: Colorectal cancer (CRC) screening decisions for elderly individuals are often made primarily on the basis of age, whereas other factors that influence the effectiveness and cost effectiveness of screening are often not considered. We investigated the relative importance of factors that could be used to identify elderly individuals most likely to benefit from CRC screening and determined the maximum ages at which screening remains cost effective based on these factors. METHODS: We used a microsimulation model (Microsimulation Screening Analysis-Colon) calibrated to the incidence of CRC in the United States and the prevalence of adenomas reported in autopsy studies to determine the appropriate age at which to stop colonoscopy screening in 19,200 cohorts (of 10 million individuals), defined by sex, race, screening history, background risk for CRC, and comorbidity status. We applied a willingness-to-pay threshold of $100,000 per quality-adjusted life-year (QALY) gained. RESULTS: Less intensive screening history, higher background risk for CRC, and fewer comorbidities were associated with cost-effective screening at older ages. Sex and race had only a small effect on the appropriate age to stop screening. For some individuals likely to be screened in current practice (for example, 74-year-old white women with moderate comorbidities, half the average background risk for CRC, and negative findings from a screening colonoscopy 10 years previously), screening resulted in a loss of QALYs, rather than a gain. For some individuals unlikely to be screened in current practice (for example, 81-year-old black men with no comorbidities, an average background risk for CRC, and no previous screening), screening was highly cost effective. Although screening some previously screened, low-risk individuals was not cost effective even when they were 66 years old, screening some healthy, high-risk individuals remained cost effective until they reached the age of 88 years old. CONCLUSIONS: The current approach to CRC screening in elderly individuals, in which decisions are often based primarily on age, is inefficient, resulting in underuse of screening for some and overuse of screening for others. CRC screening could be more effective and cost effective if individual factors for each patient are considered.

Variation in Adenoma Detection Rate and the Lifetime Benefits and Cost of Colorectal Cancer Screening: A Microsimulation Model.

IMPORTANCE: Colonoscopy is the most commonly used colorectal cancer screening test in the United States. Its quality, as measured by adenoma detection rates (ADRs), varies widely among physicians, with unknown consequences for the cost and benefits of screening programs. OBJECTIVE: To estimate the lifetime benefits, complications, and costs of an initial colonoscopy screening program at different levels of adenoma detection. DESIGN, SETTING, AND PARTICIPANTS: Microsimulation modeling with data from a community-based health care system on ADR variation and cancer risk among 57,588 patients examined by 136 physicians from 1998 through 2010. EXPOSURES: Using modeling, no screening was compared with screening initiation with colonoscopy according to ADR quintiles (averages 15.3%, quintile 1; 21.3%, quintile 2; 25.6%, quintile 3; 30.9%, quintile 4; and 38.7%, quintile 5) at ages 50, 60, and 70 years with appropriate surveillance of patients with adenoma. MAIN OUTCOMES AND MEASURES: Estimated lifetime colorectal cancer incidence and mortality, number of colonoscopies, complications, and costs per 1000 patients, all discounted at 3% per year and including 95% confidence intervals from multiway probabilistic sensitivity analysis. RESULTS: In simulation modeling, among unscreened patients the lifetime risk of colorectal cancer incidence was 34.2 per 1000 (95% CI, 25.9-43.6) and risk of mortality was 13.4 per 1000 (95% CI, 10.0-17.6). Among screened patients, simulated lifetime incidence decreased with lower to higher ADRs (26.6; 95% CI, 20.0-34.3 for quintile 1 vs 12.5; 95% CI, 9.3-16.5 for quintile 5) as did mortality (5.7; 95% CI, 4.2-7.7 for quintile 1 vs 2.3; 95% CI, 1.7-3.1 for quintile 5). Compared with quintile 1, simulated lifetime incidence was on average 11.4% (95% CI, 10.3%-11.9%) lower for every 5 percentage-point increase of ADRs and for mortality, 12.8% (95% CI, 11.1%-13.7%) lower. Complications increased from 6.0 (95% CI, 4.0-8.5) of 2777 colonoscopies (95% CI, 2626-2943) in quintile 1 to 8.9 (95% CI, 6.1-12.0) complications of 3376 (95% CI, 3081-3681) colonoscopies in quintile 5. Estimated net screening costs were lower from quintile 1 (US $2.1 million, 95% CI, $1.8-$2.4 million) to quintile 5 (US $1.8 million, 95% CI, $1.3-$2.3 million) due to averted cancer treatment costs. Results were stable across sensitivity analyses. CONCLUSIONS AND RELEVANCE: In this microsimulation modeling study, higher adenoma detection rates in screening colonoscopy were associated with lower lifetime risks of colorectal cancer and colorectal cancer mortality without being associated with higher overall costs. Future research is needed to assess whether increasing adenoma detection would be associated with improved patient outcomes.

Cost-Savings to Medicare From Pre-Medicare Colorectal Cancer Screening.

BACKGROUND: Many individuals have not received recommended colorectal cancer (CRC) screening before they become Medicare eligible at the age of 65. We aimed to estimate the long-term implications of increased CRC screening in the pre-Medicare population (50-64 y) on costs in the pre-Medicare and Medicare populations (65+ y). METHODS: We used 2 independently developed microsimulation models [Microsimulation Screening Analysis Colon (MISCAN) and Simulation Model of CRC (SimCRC)] to project CRC screening and treatment costs under 2 scenarios, starting in 2010: "current trends" (60% of the population up-to-date with screening recommendations) and "enhanced participation" (70% up-to-date). The population was scaled to the projected US population for each year between 2010 and 2060. Costs per year were derived by age group (50-64 and 65+ y). RESULTS: By 2060, the discounted cumulative total costs in the pre-Medicare population were $35.7 and $28.1 billion higher with enhanced screening participation, than in the current trends scenario ($252.1 billion with MISCAN and $239.5 billion with SimCRC, respectively). Because of CRC treatment savings with enhanced participation, cumulative costs in the Medicare population were $18.3 and $32.7 billion lower (current trends: $423.5 billion with MISCAN and $372.8 billion with SimCRC). Over the 50-year time horizon an estimated 60% (MISCAN) and 89% (SimCRC) of the increased screening costs could be offset by savings in Medicare CRC treatment costs. CONCLUSION: Increased CRC screening participation in the pre-Medicare population could reduce CRC incidence and mortality, whereas the additional screening costs can be largely offset by long-term Medicare treatment savings.

The value of models in informing resource allocation in colorectal cancer screening: the case of The Netherlands.

In May 2011, the Dutch government decided to implement a national programme for colorectal cancer (CRC) screening using biennial faecal immunochemical test screening between ages 55 and 75. Decision modelling played an important role in informing this decision, as well as in the planning and implementation of the programme afterwards. In this overview, we illustrate the value of models in informing resource allocation in CRC screening using the role that decision modelling has played in the Dutch CRC screening programme as an example.

Optimal colorectal cancer screening in states' low-income, uninsured populations­the case of South Carolina.

OBJECTIVE: To determine whether, given a limited budget, a state's low-income uninsured population would have greater benefit from a colorectal cancer (CRC) screening program using colonoscopy or fecal immunochemical testing (FIT). DATA SOURCES/STUDY SETTING: South Carolina's low-income, uninsured population. STUDY DESIGN: Comparative effectiveness analysis using microsimulation modeling to estimate the number of individuals screened, CRC cases prevented, CRC deaths prevented, and life-years gained from a screening program using colonoscopy versus a program using annual FIT in South Carolina's low-income, uninsured population. This analysis assumed an annual budget of $1 million and a budget availability of 2 years as a base case. PRINCIPAL FINDINGS: The annual FIT screening program resulted in nearly eight times more individuals being screened, and more important, approximately four times as many CRC deaths prevented and life-years gained than the colonoscopy screening program. Our results were robust for assumptions concerning economic perspective and the target population, and they may therefore be generalized to other states and populations. CONCLUSIONS: A FIT screening program will prevent more CRC deaths than a colonoscopy-based program when a state's budget for CRC screening supports screening of only a fraction of the target population.

The appropriateness of more intensive colonoscopy screening than recommended in Medicare beneficiaries: a modeling study.

IMPORTANCE: Many Medicare beneficiaries undergo more intensive colonoscopy screening than recommended. Whether this is favorable for beneficiaries and efficient from a societal perspective is uncertain. OBJECTIVE: To determine whether more intensive colonoscopy screening than recommended is favorable for Medicare beneficiaries (ie, whether it results in a net health benefit) and whether it is efficient from a societal perspective (ie, whether the net health benefit justifies the additional resources required). DESIGN, SETTING, AND PARTICIPANTS: Microsimulation modeling study of 65-year-old Medicare beneficiaries at average risk for colorectal cancer (CRC) and with an average life expectancy who underwent a screening colonoscopy at 55 years with negative results. INTERVENTIONS: Colonoscopy screening as recommended by guidelines (ie, at 65 and 75 years) vs scenarios with a shorter screening interval (5 or 3 instead of 10 years) or in which screening was continued to 85 or 95 years. MAIN OUTCOMES AND MEASURES: Quality-adjusted life-years (QALYs) gained (measure of net health benefit); additional colonoscopies required per additional QALY gained and additional costs per additional QALY gained (measures of efficiency). RESULTS: Screening previously screened Medicare beneficiaries more intensively than recommended resulted in only small increases in CRC deaths prevented and life-years gained. In comparison, the increases in colonoscopies performed and colonoscopy-related complications experienced were large. As a result, all scenarios of more intensive screening than recommended resulted in a loss of QALYs, rather than a gain (ie, a net harm). The only exception was shortening the screening interval from 10 to 5 years, which resulted in 0.7 QALYs gained per 1000 beneficiaries. However, this scenario was inefficient because it required no less than 909 additional colonoscopies and an additional $711 000 per additional QALY gained. Results in previously unscreened beneficiaries were slightly less unfavorable, but conclusions were identical. CONCLUSIONS AND RELEVANCE: Screening Medicare beneficiaries more intensively than recommended is not only inefficient from a societal perspective; often it is also unfavorable for those being screened. This study provides evidence and a clear rationale for clinicians and policy makers to actively discourage this practice.

Should colorectal cancer screening be considered in elderly persons without previous screening? A cost-effectiveness analysis.

BACKGROUND: The U.S. Preventive Services Task Force recommends against routine screening for colorectal cancer (CRC) in adequately screened persons older than 75 years but does not address the appropriateness of screening in elderly persons without previous screening. OBJECTIVE: To determine at what ages CRC screening should be considered in unscreened elderly persons and to determine which test is indicated at each age. DESIGN: Microsimulation modeling study. DATA SOURCES: Observational and experimental studies. TARGET POPULATION: Unscreened persons aged 76 to 90 years with no, moderate, and severe comorbid conditions. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION: One-time colonoscopy, sigmoidoscopy, or fecal immunochemical test (FIT) screening. OUTCOME MEASURES: Quality-adjusted life-years gained, costs, and costs per quality-adjusted life-year gained. RESULTS OF BASE-CASE ANALYSIS: In unscreened elderly persons with no comorbid conditions, CRC screening was cost-effective up to age 86 years. Screening with colonoscopy was indicated up to age 83 years, sigmoidoscopy was indicated at age 84 years, and FIT was indicated at ages 85 and 86 years. In unscreened persons with moderate comorbid conditions, screening was cost-effective up to age 83 years (colonoscopy indicated up to age 80 years, sigmoidoscopy at age 81 years, and FIT at ages 82 and 83 years). In unscreened persons with severe comorbid conditions, screening was cost-effective up to age 80 years (colonoscopy indicated up to age 77 years, sigmoidoscopy at age 78 years, and FIT at ages 79 and 80 years). RESULTS OF SENSITIVITY ANALYSES: Results were most sensitive to assuming a lower willingness to pay per quality-adjusted life-year gained. LIMITATION: Only persons at average risk for CRC were considered. CONCLUSION: In unscreened elderly persons CRC screening should be considered well beyond age 75 years. A colonoscopy is indicated at most ages. PRIMARY FUNDING SOURCE: National Cancer Institute.

Multicohort models in cost-effectiveness analysis: why aggregating estimates over multiple cohorts can hide useful information.

BACKGROUND: Models used in cost-effectiveness analysis (CEA) of screening programs may include 1 or many birth cohorts of patients. As many screening programs involve multiple screens over many years for each birth cohort, the actual implementation of screening often involves multiple concurrent recipient cohorts. Consequently, some advocate modeling all recipient cohorts rather than 1 birth cohort, arguing it more accurately represents actual implementation. However, reporting the cost-effectiveness estimates for multiple cohorts on aggregate rather than per cohort will fail to account for any heterogeneity in cost-effectiveness between cohorts. Such heterogeneity may be policy relevant where there is considerable variation in cost-effectiveness between cohorts, as in the case of cancer screening programs with multiple concurrent recipient birth cohorts, each at different stages of screening at any one point in time. OBJECTIVE: The purpose of this study is to illustrate the potential disadvantages of aggregating cost-effectiveness estimates over multiple cohorts, without first considering the disaggregate estimates. Analysis. We estimate the cost-effectiveness of 2 alternative cervical screening tests in a multicohort model and compare the aggregated and per-cohort estimates. We find instances in which the policy choices suggested by the aggregate and per-cohort results differ. We use this example to illustrate a series of potential disadvantages of aggregating CEA estimates over cohorts. CONCLUSIONS: Recent recommendations that CEAs should consider the cost-effectiveness of more than just a single cohort appear justified, but the aggregation of estimates across multiple cohorts into a single estimate does not.

Cost-effectiveness of one versus two sample faecal immunochemical testing for colorectal cancer screening.

OBJECTIVE: The sensitivity and specificity of a single faecal immunochemical test (FIT) are limited. The performance of FIT screening can be improved by increasing the screening frequency or by providing more than one sample in each screening round. This study aimed to evaluate if two-sample FIT screening is cost-effective compared with one-sample FIT. DESIGN: The MISCAN-colon microsimulation model was used to estimate costs and benefits of strategies with either one or two-sample FIT screening. The FIT cut-off level varied between 50 and 200 ng haemoglobin/ml, and the screening schedule was varied with respect to age range and interval. In addition, different definitions for positivity of the two-sample FIT were considered: at least one positive sample, two positive samples, or the mean of both samples being positive. RESULTS: Within an exemplary screening strategy, biennial FIT from the age of 55-75 years, one-sample FIT provided 76.0-97.0 life-years gained (LYG) per 1000 individuals, at a cost of € 259,000-264,000 (range reflects different FIT cut-off levels). Two-sample FIT screening with at least one sample being positive provided 7.3-12.4 additional LYG compared with one-sample FIT at an extra cost of € 50,000-59,000. However, when all screening intervals and age ranges were considered, intensifying screening with one-sample FIT provided equal or more LYG at lower costs compared with two-sample FIT. CONCLUSION: If attendance to screening does not differ between strategies it is recommended to increase the number of screening rounds with one-sample FIT screening, before considering increasing the number of FIT samples provided per screening round.

Liquid-based cervical cytology using ThinPrep technology: weighing the pros and cons in a cost-effectiveness analysis.

PURPOSE: Cervical cancer screening with liquid-based cytology (LBC) has been developed as an alternative to the conventional Papanicolaou (CP) smear. Cost-effectiveness is one of the issues when evaluating LBC. Based on the results of a Dutch randomised controlled trial, we conducted cost-effectiveness threshold analyses to investigate under what circumstances manually screened ThinPrep LBC is cost-effective for screening. METHODS: The MISCAN-Cervix microsimulation model and data from the Dutch NETHCON trial (including 89,784 women) were used to estimate the costs and (quality-adjusted) life years ((QA)LYs) gained for EU screening schedules, varying cost-effectiveness threshold values. Screening strategies were primary cytological screening with LBC or CP, and triage with human papillomavirus (HPV) testing. RESULTS: Threshold analyses showed that screening with LBC as a primary test can be cost-effective if LBC is less than 3.2 more costly per test than CP, if the sensitivity of LBC is at least 3-5 % points higher than CP, if the quality of life for women in triage follow-up is only 0.39, or if the rate of inadequate CP smears is at least 16.2 %. CONCLUSIONS: Regarding test characteristics and costs of LBC and CP, only under certain conditions will a change from CP to manually screened ThinPrep LBC be cost-effective. If none of these conditions are met, implementation of manually screened ThinPrep LBC seems warranted only if there are advantages other than cost-effectiveness. Further research is needed to establish whether other LBC systems will be more favorable with regard to cost-effectiveness.

Contribution of screening and survival differences to racial disparities in colorectal cancer rates.

BACKGROUND: Considerable disparities exist in colorectal cancer (CRC) incidence and mortality rates between blacks and whites in the United States. We estimated how much of these disparities could be explained by differences in CRC screening and stage-specific relative CRC survival. METHODS: We used the MISCAN-Colon microsimulation model to estimate CRC incidence and mortality rates in blacks, aged 50 years and older, from 1975 to 2007 assuming they had: (i) the same trends in screening rates as whites instead of observed screening rates (incidence and mortality); (ii) the same trends in stage-specific relative CRC survival rates as whites instead of observed (mortality only); and (iii) a combination of both. The racial disparities in CRC incidence and mortality rates attributable to differences in screening and/or stage-specific relative CRC survival were then calculated by comparing rates from these scenarios to the observed black rates. RESULTS: Differences in screening accounted for 42% of disparity in CRC incidence and 19% of disparity in CRC mortality between blacks and whites. Thirty-six percent of the disparity in CRC mortality could be attributed to differences in stage-specific relative CRC survival. Together screening and survival explained a little more than 50% of the disparity in CRC mortality between blacks and whites. CONCLUSION: Differences in screening and relative CRC survival are responsible for a considerable proportion of the observed disparities in CRC incidence and mortality rates between blacks and whites. IMPACT: Enabling blacks to achieve equal access to care as whites could substantially reduce the racial disparities in CRC burden.

Primary screening for human papillomavirus compared with cytology screening for cervical cancer in European settings: cost effectiveness analysis based on a Dutch microsimulation model.

OBJECTIVES: To investigate, using a Dutch model, whether and under what variables framed for other European countries screening for human papillomavirus (HPV) is preferred over cytology screening for cervical cancer, and to calculate the preferred number of examinations over a woman's lifetime. DESIGN: Cost effectiveness analysis based on a Dutch simulation model. Base case analyses investigated the cost effectiveness of more than 1500 different screening policies using the microsimulation model. Subsequently, the policies were compared for five different scenarios that represent different possible scenarios (risk of cervical cancer, previous screening, quality associated test characteristics, costs of testing, and prevalence of HPV). SETTING: Various European countries. POPULATION: Unvaccinated women born between 1939 and 1992. MAIN OUTCOME MEASURES: Optimal screening strategy in terms of incremental cost effectiveness ratios (costs per quality adjusted life years gained) compared with different cost effectiveness thresholds, for two levels of sensitivity and costs of the HPV test. RESULTS: Primary HPV screening was the preferred primary test over the age of 30 in many considered scenarios. Primary cytology screening was preferred only in scenarios with low costs of cytology and in scenarios with a high prevalence of HPV in combination with high costs of HPV testing. CONCLUSIONS: Most European countries should consider switching from primary cytology to HPV screening for cervical cancer. HPV screening must, however, only be implemented in situations where screening is well controlled.