scholarly journals Estimating the impact of differential adherence on the comparative effectiveness of stool-based colorectal cancer screening using the CRC-AIM microsimulation model

2020 ◽  
Author(s):  
Andrew Piscitello ◽  
Leila Saoud ◽  
A. Mark Fendrick ◽  
Bijan J. Borah ◽  
Kristen Hassmiller Lich ◽  
...  

AbstractBackgroundReal-world adherence to colorectal cancer (CRC) screening strategies is imperfect. The CRC-AIM microsimulation model was used to estimate the impact of imperfect adherence on the relative benefits and burdens of guideline-endorsed, stool-based screening strategies.MethodsPredicted outcomes of multi-target stool DNA (mt-sDNA), fecal immunochemical tests (FIT), and high-sensitivity guaiac-based fecal occult blood tests (HSgFOBT) were simulated for 40-year-olds free of diagnosed CRC. For robustness, imperfect adherence was incorporated in multiple ways and with extensive sensitivity analysis. Analysis 1 assumed adherence from 0%-100%, in 10% increments. Analysis 2 longitudinally applied real-world first-round differential adherence rates (base-case imperfect rates=40% annual FIT vs 34% annual HSgFOBT vs 70% triennial mt-sDNA). Analysis 3 randomly assigned individuals to receive 1, 5, or 9 lifetime (9=100% adherence) mt-sDNA tests and 1, 5, or 9 to 26 (26=100% adherence) FIT tests. Outcomes are reported per 1000 individuals compared with no screening.ResultsEach screening strategy decreased CRC incidence and mortality versus no screening. In individuals screened between ages 50-75 and adherence ranging from 10%-100%, the life-years gained (LYG) for triennial mt-sDNA ranged from 133.1-300.0, for annual FIT from 96.3-318.1, and for annual HSgFOBT from 99.8-320.6. At base-case imperfect adherence rates, mt-sDNA resulted in 19.1% more LYG versus FIT, 25.4% more LYG versus HSgFOBT, and generally had preferable efficiency ratios while offering the most LYG. Completion of at least 21 FIT tests is needed to reach approximately the same LYG achieved with 9 mt-sDNA tests.ConclusionsAdherence assumptions affect the conclusions of CRC screening microsimulations that are used to inform CRC screening guidelines. LYG from FIT and HSgFOBT are more sensitive to changes in adherence assumptions than mt-sDNA because they require more tests be completed for equivalent benefit. At imperfect adherence rates, mt-sDNA provides more LYG than FIT or HSgFOBT at an acceptable tradeoff in screening burden.

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0244431
Author(s):  
Andrew Piscitello ◽  
Leila Saoud ◽  
A. Mark Fendrick ◽  
Bijan J. Borah ◽  
Kristen Hassmiller Lich ◽  
...  

Background Real-world adherence to colorectal cancer (CRC) screening strategies is imperfect. The CRC-AIM microsimulation model was used to estimate the impact of imperfect adherence on the relative benefits and burdens of guideline-endorsed, stool-based screening strategies. Methods Predicted outcomes of multi-target stool DNA (mt-sDNA), fecal immunochemical tests (FIT), and high-sensitivity guaiac-based fecal occult blood tests (HSgFOBT) were simulated for 40-year-olds free of diagnosed CRC. For robustness, imperfect adherence was incorporated in multiple ways and with extensive sensitivity analysis. Analysis 1 assumed adherence from 0%-100%, in 10% increments. Analysis 2 longitudinally applied real-world first-round differential adherence rates (base-case imperfect rates = 40% annual FIT vs 34% annual HSgFOBT vs 70% triennial mt-sDNA). Analysis 3 randomly assigned individuals to receive 1, 5, or 9 lifetime (9 = 100% adherence) mt-sDNA tests and 1, 5, or 9 to 26 (26 = 100% adherence) FIT tests. Outcomes are reported per 1000 individuals compared with no screening. Results Each screening strategy decreased CRC incidence and mortality versus no screening. In individuals screened between ages 50–75 and adherence ranging from 10%a-100%, the life-years gained (LYG) for triennial mt-sDNA ranged from 133.1–300.0, for annual FIT from 96.3–318.1, and for annual HSgFOBT from 99.8–320.6. At base-case imperfect adherence rates, mt-sDNA resulted in 19.1% more LYG versus FIT, 25.4% more LYG versus HSgFOBT, and generally had preferable efficiency ratios while offering the most LYG. Completion of at least 21 FIT tests is needed to reach approximately the same LYG achieved with 9 mt-sDNA tests. Conclusions Adherence assumptions affect the conclusions of CRC screening microsimulations that are used to inform CRC screening guidelines. LYG from FIT and HSgFOBT are more sensitive to changes in adherence assumptions than mt-sDNA because they require more tests be completed for equivalent benefit. At imperfect adherence rates, mt-sDNA provides more LYG than FIT or HSgFOBT at an acceptable tradeoff in screening burden.


2019 ◽  
Vol 29 (Supplement_4) ◽  
Author(s):  
E D’Andrea ◽  
D J Ahnen ◽  
D A Sussman ◽  
M Najafzadeh

Abstract Background Current recommendations of The US Preventive Services Task Force (USPSTF) on colorectal cancer (CRC) screening strategies are based on models that assume 100% adherence to screening. Since adherence can largely affect the outcomes of a screening modality, we aimed to assess the comparative effectiveness of CRC screening strategies under published rates of actual adherence. Methods We developed an individual-level simulation model and validated it against landmark trials and USPSTF models. Then we assessed the effectiveness of colonoscopy (COL), flexible sigmoidoscopy (FS), high-sensitivity guaiac fecal occult blood test (HS-gFOBT), fecal immunochemical test (FIT), multitarget stool DNA test (FIT-DNA), computed tomography colonography (CTC), and methylated SEPT9 DNA test (SEPT9) in reducing CRC incidence and mortality. For each strategy, we also estimated the incremental life-years gained, number of colonoscopies, and adverse events. Results Assuming 100% adherence, FIT-DNA, FIT, HS-gFOBT, and SEPT9 averted 58 to 59 CRC cases and 28 CRC deaths; COL and CTC strategies 56 cases and 27 deaths, while FS averted 39 cases and 19 deaths per 1,000 individuals. Life-years gained were similar across FIT-DNA, FIT, HS-gFOBT, SEPT9, CTC, and COL strategies. The total number of colonoscopies was highest with COL (3,567), followed by SEPT9 (3,231), HS-gFOBT (2,584), FIT-DNA (2,079), FIT (2,067), CTC (1,691) and FS (1,538) strategies. Assuming actual adherence, SEPT9 averted 54 CRC cases and 26 CRC deaths, followed by COL with 49 cases and 24 deaths, and FIT-DNA, FIT, CTC and HS-gFOBT with approximately 36 to 41 cases and 18 to 21 deaths averted per 1000 individuals screened. Life-years gained reflected the effectiveness of each strategy in reducing CRC cases and deaths. Conclusions Adherence is a key factor in determining the effectiveness of CRC screening and strategies with higher expected adherence rates have the potential to reduce cancer incidence and mortality. Key messages Adherence has a substantial impact on screening outcomes, such as cancer incidence and mortality, and may influence selection of optimal screening strategies. Strategies with higher expected adherence rates can lead to clinically meaningful benefits compared to strategies that may have better one-time sensitivity and/or specificity.


2020 ◽  
Author(s):  
Deborah A. Fisher ◽  
Leila Saoud ◽  
Kristen Hassmiller Lich ◽  
A. Mark Fendrick ◽  
A. Burak Ozbay ◽  
...  

AbstractBackgroundReal-world data for patients with positive colorectal cancer (CRC) screening stool-tests demonstrates that adenoma detection rates are lower when endoscopists are blinded to the stool-test results. This suggests adenoma sensitivity may be lower for screening colonoscopy than for follow-up to a known positive stool-based test. Previous CRC microsimulation models assume identical sensitivities between screening and follow-up colonoscopies after positive stool-tests. The Colorectal Cancer and Adenoma Incidence and Mortality Microsimulation Model (CRC-AIM) was used to explore the impact on screening outcomes when assuming different adenoma sensitivity between screening and combined follow-up/surveillance colonoscopies.MethodsModeled screening strategies included colonoscopy every 10 years, triennial multitarget stool DNA (mt-sDNA), or annual fecal immunochemical test (FIT) from 50-75 years. Outcomes were reported per 1,000 individuals without diagnosed CRC at age 40. Base-case adenoma sensitivity values were identical for screening and follow-up/surveillance colonoscopies. Ranges of adenoma sensitivity values for colonoscopy performance were developed using different slopes of odds ratio adjustments and were designated as small, medium, or large impact scenarios.ResultsAs the differences in adenoma sensitivity for screening versus follow-up/surveillance colonoscopies became greater, life-years gained (LYG) and reductions in CRC-related incidence and mortality versus no screening increased for mt-sDNA and FIT and decreased for screening colonoscopy. The LYG relative to screening colonoscopy reached >90% with FIT in the base-case scenario and with mt-sDNA in a “medium impact” scenario.ConclusionsAssuming identical adenoma sensitivities for screening and follow-up/surveillance colonoscopies underestimates the potential benefits of stool-based screening strategies.


2019 ◽  
pp. 1-10
Author(s):  
Gregory C. Knapp ◽  
Olusegun I. Alatise ◽  
Olalekan O. Olasehinde ◽  
Ademola Adeyeye ◽  
Omobolaji O. Ayandipo ◽  
...  

PURPOSE The global burden of colorectal cancer (CRC) will continue to increase for the foreseeable future, largely driven by increasing incidence and mortality in low- and middle-income countries (LMICs) such as Nigeria. METHODS We used the Wilson-Jungner framework (1968) to review the literature relevant to CRC screening in Nigeria and propose areas for future research and investment. RESULTS Screening is effective when the condition sought is both important and treatable within the system under evaluation. The incidence of CRC is likely increasing, although the exact burden of disease in Nigeria remains poorly understood and access to definitive diagnosis and treatment has not been systematically quantified. In high-income countries (HICs), CRC screening builds on a well-known natural history. In Nigeria, a higher proportion of CRC seems to demonstrate microsatellite instability, which is dissimilar to the molecular profile in HICs. Prospective trials, tissue banking, and next-generation sequencing should be leveraged to better understand these potential differences and the implications for screening. Fecal immunochemical test for hemoglobin (FIT) is recommended for LMICs that are considering CRC screening. However, FIT has not been validated in Nigeria, and questions about the impact of high ambient temperature, endemic parasitic infection, and feasibility remain unanswered. Prospective trials are needed to validate the efficacy of stool-based screening, and these trials should consider concomitant ova and parasite testing. CONCLUSION Using the Wilson-Jungner framework, additional work is needed before organized CRC screening will be effective in Nigeria. These deficits can be addressed without missing the window to mitigate the increasing burden of CRC in the medium to long term.


2020 ◽  
Vol 71 (1) ◽  
pp. 59-69 ◽  
Author(s):  
John M. Carethers

Fecal (or stool) DNA examination is a noninvasive strategy recommended by several medical professional societies for colorectal cancer (CRC) screening in average-risk individuals. Fecal DNA tests assay stool for human DNA shed principally from the colon. Colonic lesions such as adenomatous and serrated polyps and cancers exfoliate cells containing neoplastically altered DNA that may be detected by sensitive assays that target specific genetic and epigenetic biomarkers to discriminate neoplastic lesions from non-neoplastic tissue. Cross-sectional validation studies confirmed initial case-control studies’ assessment of performance of an optimized multitarget stool DNA (mt-sDNA) test, leading to approval by the US Food and Drug Administration in 2014. Compared to colonoscopy, mt-sDNA showed sensitivity of 92% for detection of CRC, much higher than the 74% sensitivity of another recommended noninvasive strategy, fecal immunochemical testing (FIT). Detections of advanced adenomas and sessile serrated polyps were higher with mt-sDNA than FIT (42% versus 24% and 42% versus 5%, respectively), but overall specificity for all lesions was lower (87% versus 95%). The mt-sDNA test increases patient life-years gained in CRC screening simulations, but its cost relative to other screening strategies needs to be reduced by 80–90% or its sensitivity for polyp detection enhanced to be cost effective. Noninvasive CRC screening strategies such as fecal DNA, however, have the potential to significantly increase national screening rates due to their noninvasive nature and convenience for patients.


2008 ◽  
Vol 23 (2) ◽  
pp. 97-100 ◽  
Author(s):  
Aimee S. James ◽  
Sandra Hall ◽  
K. Allen Greiner ◽  
Dan Buckles ◽  
Wendi K. Born ◽  
...  

Purpose. Colorectal cancer (CRC) screening is effective, but only one-half of age-eligible adults adhere to national guidelines. Lower socioeconomic status (SES) groups are less likely to be screened. Methods. Baseline data from a prospective study were used to examine the associations among CRC screening screening barriers, and SES. A convenience sample of adults (N = 291) aged 40 years and older was recruited from a federally qualified health center. Questionnaires were administered orally and included demographics, health, health behavior, and screening barriers. Results. In logistic regression, having health insurance was associated with greater odds of screening. Bivariate analyses detected few differences in fecal occult blood test (FOBT) barriers, but several endoscopy barriers were more common among the lowest SES groups. For example, fear of injury from endoscopy was more likely among low-income and uninsured participants. Discussion. The impact of SES on cancer screening is complex, but low-SES participants more often reported certain barriers than their higher-SES counterparts. This was more evident for endoscopy than for FOBT. Programs targeted at low-SES patients may need to focus on barriers that are not fully addressed in traditional promotion efforts.


2019 ◽  
Vol 9 (2) ◽  
pp. 824-836 ◽  
Author(s):  
Elvira D’Andrea ◽  
Dennis J. Ahnen ◽  
Daniel A. Sussman ◽  
Mehdi Najafzadeh

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3531-3531
Author(s):  
Myrtle F Krul ◽  
Marloes AG Elferink ◽  
Niels FM Kok ◽  
Evelien Dekker ◽  
Iris Lansdorp-Vogelaar ◽  
...  

3531 Background: Population-based screening for colorectal cancer (CRC) aims to decrease incidence and mortality due to precancerous polyp removal, early detection and early treatment of CRC. In the Netherlands, phased introduction of a biennial fecal immunochemical hemoglobin test started in 2014 for individuals aged 55-75. This evaluation of the national data focuses on the initial effect of CRC screening on incidence and stage distribution and the impact on stage IV disease. Methods: All CRC patients diagnosed in the Netherlands between 2009 and 2018 were selected from the Netherlands Cancer Registry (NCR). Patients were linked to the Dutch national pathology registry (PALGA) to identify screen-detected tumors. Results: The NCR identified 137,717 CRC patients between 2009 and 2018. The incidence within screening age (55-75 yr) of all CRC stages showed an initial peak after introduction of screening in 2014, followed by a continuous decrease for all stages. CRC incidence outside the screening age did not show these explicit changes between 2009 and 2018. In 2018, the incidence of stage IV CRC within screening age was lower than the level at the start of the screening program. Stage distribution within screening age shifted towards earlier stages in the screening period (2014-2018) compared to the period before screening (2009-2012) (stage I: 31% vs. 18%, stage II: 22% vs. 26%, stage III: 29% vs. 31%, Stage IV: 18% vs. 25%, respectively). In the period 2014-2018 and within screening age, the ratio of screen-detected and symptom-detected tumors was highest in stage I (47%:53%) and lowest in stage IV (9%:91%). Screen-detected compared to symptom-detected stage IV patients diagnosed in the period 2014-2018 and within screening age had more frequently single organ metastases (74.5% vs 57.4%, p < 0.001), higher resection rate of the primary tumor (57.5% vs. 41.3%; p < 0.001) and higher local treatment rate of metastases (40.0% vs. 23.4% p < 0.001). The median overall survival of screen-detected stage IV patients was significantly longer than that of symptom-detected stage IV patients (31.0 months (95% CI: 27.7 – 34.3) vs. 15.0 months (95% CI: 14.5 – 15.5), p < 0.001). Conclusions: The initial results of the introduction of CRC screening in the Netherlands showed a favorable trend on CRC incidence and stage distribution. Screen-detected patients with stage IV disease had less extensive disease, resulting in better treatment options and improved survival.


2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Justin L. Sovich ◽  
Zachary Sartor ◽  
Subhasis Misra

Background.Worldwide, colorectal cancer (CRC) is the third most common cancer in men and second most common in women. It is the fourth most common cause of cancer mortality. In the United States, CRC is the third most common cause of cancer and second most common cause of cancer mortality. Incidence and mortality rates have steadily fallen, primarily due to widespread screening.Methods.We conducted keyword searches on PubMed in four categories of CRC screening: stool, endoscopic, radiologic, and serum, as well as news searches in Medscape and Google News.Results.Colonoscopy is the gold standard for CRC screening and the most common method in the United States. Technological improvements continue to be made, including the promising “third-eye retroscope.” Fecal occult blood remains widely used, particularly outside the United States. The first at-home screen, a fecal DNA screen, has also recently been approved. Radiological methods are effective but seldom used due to cost and other factors. Serum tests are largely experimental, although at least one is moving closer to market.Conclusions.Colonoscopy is likely to remain the most popular screening modality for the immediate future, although its shortcomings will continue to spur innovation in a variety of modalities.


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