Estimated impact and value of blood-based colorectal cancer screening at varied adherence compared with stool-based screening.

OBJECTIVE: This analysis estimated the outcomes of triennial blood-based colorectal cancer (CRC) screening at various adherence, including perfect adherence, compared with triennial multi-target stool DNA (mt-sDNA) screening at the reported real-world adherence rate. METHODS: The validated CRC-AIM model simulated a US cohort of average-risk individuals receiving triennial screening with mt-sDNA or blood-based test from ages 45 to 75 years. Modeled specificity and sensitivity were based on reported data. Adherence was set at a real-world rate of 65.6% for mt-sDNA and at 65.6%, relative 10% incremental increases from 65.6%, or 100% for the blood-based test. Costs of mt-sDNA and the blood-based test were based on prices for clinically available tests ($508.87 and $895, respectively). Value-based pricing was estimated at a willingness-to-pay threshold of $100,000. RESULTS: Both tests resulted in life-years gained (LYG), reduced CRC cases, and reduced deaths versus no screening. With adherence for mt-sDNA set at 65.6% and for blood-based test set at 100%, mt-sDNA resulted in 30% more LYG, 52% more averted CRC cases, and 32% more averted CRC deaths. At reported sensitivity and specificity rates, mt-sDNA at 65.6% adherence dominates (is more effective and less costly) the blood-based test at any adherence. There was no price at which triennial screening with the blood-based test at any adherence was cost-effective compared with mt-sDNA at 65.6% adherence. CONCLUSIONS: Triennial screening with mt-sDNA resulted in better clinical outcomes at a lower cost compared with the modeled blood-based test even at perfect adherence, supporting application of blood-based tests only as a secondary screening option.

Blood-based colorectal cancer screening has lower diagnostic accuracy, lower clinical and health outcomes, and is more expensive than mt-sDNA, even with perfect blood-based screening participation. Although better than no screening at all, blood-based testing is unlikely to exceed performance of stool-based assessment unless a blood-based test is able to meaningfully detect precancerous growths.

Trends in colorectal cancer screening from the National Health Interview Survey (NHIS): analysis of the impact of different modalities on overall screening rates.

Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in adults in the United States. Despite compelling evidence of improved outcomes in CRC, screening rates are not optimal. This study aimed to characterize CRC screening trends over the last two decades and assess the impact of various screening modalities on overall CRC screening rates. Using National Health Interview Survey data from 2005-2021, we examined CRC screening (colonoscopy, mt-sDNA, FOBT/FIT, sigmoidoscopy, CT Colonography) rates among adults aged 50-75 years (n = 85,571). A pseudo-time-series cross-sectional (pseudo-TSCS) analysis was conducted including a random effects GLS regression model to estimate the relative impact of each modality on changes in CRC screening rates. Among 50-75-year-olds, the estimated CRC screening rate increased from 47.7% in 2005 to 69.9% in 2021, with the largest increase between 2005 and 2010 (47.7% to 60.7%). Rates subsequently plateaued until 2015 but increased from 63.5% in 2015 to 69.9% in 2018. This was primarily driven by the increased use of mt-sDNA (2.5% in 2018 to 6.6% in 2021). Pseudo-TSCS analysis results showed that mt-sDNA contributed substantially to the increase in overall screening rates (77.3%; p < 0.0001) between 2018-2021. While CRC screening rates increased from 2005 to 2021, they remain below the 80% goal. The introduction of mt-sDNA, a non-invasive screening test may have improved overall rates. Sustained efforts are required to further increase screening rates to improve patient outcomes and offering a range of screening options is likely to contribute to achieving this goal.

Impact of Eliminating Cost-Sharing by Medicare Beneficiaries for Follow-Up Colonoscopy After a Positive Stool-based Colorectal Cancer Screening Test.

Medicare coverage of a follow-up colonoscopy after a positive stool-based colorectal cancer screening test with no patient cost-sharing started January 2, 2023, which may favorably affect screening behavior. This analysis estimated the clinical and economic effects of increased colorectal cancer screening participation potentially resulting from this policy change in Medicare beneficiaries. The validated Colorectal Cancer and Adenoma Incidence & Mortality (CRC-AIM) model simulated three guideline-endorsed colorectal cancer screening strategies for average-risk individuals (colonoscopy every 10 years, annual fecal immunochemical test, triennial multitarget stool DNA) from ages 65-75 years. The base-case scenario assumed 0% coinsurance for initial screening and follow-up colonoscopy, real-world screening test use (colonoscopy = 45.3%, stool-based test = 24.4%, unscreened = 30.3%), and real-world follow-up colonoscopy rates. Comparative scenarios assumed an increase in the overall screening rate from 0% to 15% (5% increments) and an increase in the follow-up colonoscopy rate from 0% to 15% (5% increments). The base-case scenario resulted in 128 life-years gained (LYG)/1,000 individuals versus no screening and total screening and treatment costs of $7,938/person. The changes resulted in an increase of up to 26 LYG/1,000 individuals and a decrease in total screening and treatment costs by as much as $128/person. Follow-up colonoscopy at $0 coinsurance became cost-saving with any increase in either overall screening or follow-up colonoscopy. Policies that remove cost barriers to completing colorectal cancer screening may increase rates of screening participation, potentially improving economic and clinical outcomes. SIGNIFICANCE: A follow-up colonoscopy after a positive stool-based colorectal cancer screening test is necessary to complete the full screening process. Policies that remove cost barriers to completing colorectal cancer screening may lead to increases in overall participation rates and use of follow-up colonoscopy, improving clinical and economic outcomes.

The cost-effectiveness of non-invasive stool-based colorectal cancer screening offerings from age 45 for a commercial and medicare population.

AIM: The United States Preventive Services Taskforce (USPSTF) recently recommended lowering the age for average-risk colorectal cancer (CRC) screening from 50 to 45 years. While initiating screening at age 45 versus 50 provides a greater opportunity for CRC early detection and prevention, the full profile of benefits, risks, and cost-effectiveness of expanding the screen-eligible population requires further evaluation. MATERIALS AND METHODS: The costs and clinical outcomes for screening at age 45 for triennial multi-target stool DNA [mt-sDNA], and other non-invasive stool-based modalities (annual fecal immunochemical test [FIT] and annual fecal-occult blood test [FOBT]), were estimated using the validated CRC-AIM microsimulation model over a lifetime horizon. Test sensitivity and specificity inputs were based on 2021 USPSTF modeling analyses; adherence rates were based on published real-world data and the costs of the screening test, follow-up colonoscopies, complications, and CRC care were included. Outcomes are reported from the perspective of a United States payer as clinical, life-years gained (LYG), and incremental cost-effectiveness ratio (ICER); stool-based and follow-up colonoscopy adherence ranges were explored in one-way, probabilistic and threshold analyses. RESULTS: When compared to initiation of CRC screening at age 45 versus 50, all modalities reduced both the incidence of and mortality from CRC and increased LYG. Initiating CRC screening at age 45 was cost-effective with an ICER of $59,816 and $35,857 per quality-adjusted life year (QALY) for mt-sDNA versus FIT and FOBT, respectively. In the threshold analyses, at equivalent rates to stool-based screening, mt-sDNA was always cost-effective at a willingness-to-pay threshold of $100,000 per QALY versus FIT and FOBT. CONCLUSIONS: Initiating average-risk CRC screening at age 45 instead of age 50 increases the estimated clinical benefit by reducing disease burden while remaining cost-effective. Among stool-based screening modalities, mt-sDNA provides the most clinical benefit in a Commercial and Medicare population.

Screening for colorectal cancer at an earlier age can provide additional benefits in terms of reducing disease complications and death. This study looked at the occurrence of disease complications and costs related to different types of colorectal cancer screening in 45 vs. 50 year old people. A model that has previously been used to project lifetime costs and disease complications in people receiving colorectal cancer screening was used in this study. We found that beginning screening at age 45 as compared to at age 50 reduced disease complications and death. In people who started screening at age 45, one particular screening type (multitarget stool DNA) was found to provide better economic value to a greater degree relative to other strategies. These findings were consistent even when many inputs into the model were changed over reasonable ranges. Therefore, our study helps show that starting screening in people at age 45 with average risk for developing colorectal cancer is beneficial by reducing disease complications and deaths, and that multitarget stool DNA is the strategy that provides the most benefits while being economically justifiable.

Comparison of Simulated Outcomes Between Stool- and Blood-Based Colorectal Cancer Screening Tests.

The Centers for Medicare & Medicaid Services (CMS) recommend covering blood-based tests meeting proposed minimum performance thresholds for colorectal cancer (CRC) screening. Outcomes were compared between currently available stool-based screening tests and a hypothetical blood-based test meeting CMS minimum thresholds. Using the Colorectal Cancer and Adenoma Incidence and Mortality Microsimulation Model (CRC-AIM), outcomes were simulated for average-risk individuals screened between ages 45 and 75 years with triennial multitarget stool DNA (mt-sDNA), annual fecal immunochemical test (FIT), and annual fecal occult blood test (FOBT). Per CMS guidance, blood-based CRC screening was modeled triennially, with 74% CRC sensitivity and 90% specificity. Although not specified by CMS, adenoma sensitivity was set between 10% and 20%. Published adenoma and CRC sensitivity and specificity were used for stool-based tests. Adherence was set at (1) 100%, (2) 30%-70%, in 10% increments, and (3) real-world rates for stool-based tests (mt-sDNA = 65.6%; FIT = 42.6%; FOBT = 34.4%). Assuming perfect adherence, a blood-based test produced ≥19 lower life-years gained (LYG) than stool-based strategies. At the best-case scenario for blood-based tests (100% adherence and 20% adenoma sensitivity), mt-sDNA at real-world adherence achieved more LYG (287.2 vs. 297.1, respectively) with 14% fewer colonoscopies. At 100% blood-based test adherence and real-world mt-sDNA and FIT adherence, the blood-based test would require advanced adenoma sensitivity of 30% to reach the LYG of mt-sDNA (297.1) and ∼15% sensitivity to reach the LYG of FIT (258.9). This model suggests that blood-based tests with CMS minimally acceptable CRC sensitivity and low advanced adenoma sensitivity will frequently yield inferior outcomes to stool-based testing across a wide range of adherence assumptions.

Effectiveness of HCC surveillance programs using multitarget blood test: A modeling study.

BACKGROUND: The effectiveness of ultrasound-based surveillance for HCC in patients with cirrhosis is limited by suboptimal sensitivity for early tumor detection and poor adherence. Emerging blood-based biomarkers have been proposed as an alternative surveillance strategy. We aimed to evaluate the comparative effectiveness of a multitarget HCC blood test (mt-HBT)-with and without improved adherence-against ultrasound-based HCC surveillance. METHODS: We developed a Markov-based mathematical model that simulated a virtual trial in patients with compensated cirrhosis comparing potential surveillance strategies: biannual surveillance using ultrasound, ultrasound plus AFP, and mt-HBT with or without improved adherence (+10% increase). We used published data to inform underlying liver disease progression rates, HCC tumor growth patterns, performance characteristics of surveillance modalities, and efficacy of treatments. Primary outcomes of interest were the number of early-stage HCCs detected and life years gained. RESULTS: Per 100,000 patients with cirrhosis, mt-HBT detected 1680 more early-stage HCCs than ultrasound alone and 350 more early-stage HCCs than ultrasound + AFP, yielding an additional 5720 and 1000 life years, respectively. mt-HBT with improved adherence detected 2200 more early-stage HCCs than ultrasound and 880 more early-stage HCCs than ultrasound + AFP, yielding an additional 8140 and 3420 life years, respectively. The number of screening tests needed to detect one HCC case was 139 with ultrasound, 122 with ultrasound + AFP, 119 with mt-HBT, and 124 with mt-HBT with improved adherence. CONCLUSIONS: mt-HBT is a promising alternative to ultrasound-based HCC surveillance, particularly given anticipated improved adherence with blood-based biomarkers could increase HCC surveillance effectiveness.

Healthcare Resource Utilization and Costs Among Patients With Gastroesophageal Reflux Disease, Barrett's Esophagus, and Barrett's Esophagus-Related Neoplasia in the United States.

Background: Gastroesophageal reflux disease (GERD) is a risk factor for Barrett's esophagus (BE) and BE-related neoplasia (BERN). Objectives: This study aimed to evaluate healthcare resource utilization (HRU) and costs associated with GERD, BE, and BERN in the United States. Methods: Adult patients with GERD, nondysplastic BE (NDBE), and BERN (including indefinite for dysplasia [IND], low-grade dysplasia [LGD], high-grade dysplasia [HGD] or esophageal adenocarcinoma [EAC]), were identified from a large US administrative claims database, the IBM Truven Health MarketScan® databases (Q1/2015-Q4/2019). Patients were categorized into the corresponding mutually exclusive EAC-risk/diagnosis cohorts based on the most advanced stage from GERD to EAC using diagnosis codes in medical claims. Disease-related HRU and costs (2020 USD) were calculated for each cohort. Results: Patients were categorized into the following EAC-risk/diagnosis cohorts: 3 310 385 into GERD, 172 481 into NDBE, 11 516 into IND, 4332 into LGD, 1549 into HGD, and 11 676 into EAC. Disease-related annual mean number of inpatient admissions, office visits, and emergency department visits by cohort were 0.09, 1.45, and 0.19 for GERD; 0.08, 1.55, and 0.10 for NDBE; 0.10, 1.92, and 0.13 for IND; 0.09, 2.05, and 0.10 for LGD; 0.12, 2.16, and 0.14 for HGD; and 1.43, 6.27, and 0.87 for EAC. Disease-related annual mean total healthcare costs by cohort were $6955 for GERD, $8755 for NDBE, $9675 for IND, $12 241 for LGD, $24 239 for HGD, and $146 319 for EAC. Discussion: Patients with GERD, BE, and BERN had important HRU and costs, including inpatient admissions and office visits. As patients progressed to more advanced stages, there was substantially higher disease-related resource utilization, with associated costs being 16 times higher in patients with EAC than those with NDBE. Conclusions: Findings suggest the need for early identification of high-risk individuals prior to progression to EAC to potentially improve clinical and economic outcomes in this population.

Real-world upper endoscopy utilization patterns among patients with gastroesophageal reflux disease, Barrett esophagus, and Barrett esophagus-related esophageal neoplasia in the United States.

This study fills a gap in literature by providing contemporary real-world evidence on the prevalence of patients with gastroesophageal reflux disease (GERD), Barrett esophagus (BE), and Barrett esophagus-related neoplasia (BERN) and their upper endoscopy utilization patterns in the United States. A retrospective cohort study design was used: adults with GERD, nondysplastic Barrett esophagus (NDBE), and BERN (indefinite for dysplasia [IND], low-grade dysplasia [LGD], high-grade dysplasia [HGD], or esophageal adenocarcinoma [EAC]) were identified from the MarketScan databases (January 01, 2015-December 31, 2019). For each disease stage, prevalence of adults in commercial claims by calendar year, annual number of upper endoscopies per patient and time between upper endoscopies were reported. In 2019, in commercial claims (N = 12,363,227), the annual prevalence rate of GERD was 13.7% and 0.70% for BE/BERN, among which, 87.1% had NDBE, 6.8% had IND, 2.3% had LGD, 1.0% had HGD, and 2.8% had EAC. From 2015-2019, the study included 3,310,385 patients with GERD, 172,481 with NDBE, 11,516 with IND, 4332 with LGD, 1549 with HGD, and 11,676 with EAC. Annual mean number of upper endoscopies was 0.20 per patient for GERD, 0.37 per patient for NDBE, 0.43 for IND, 0.58 for LGD, and 0.87 for HGD. Median time (months) to second upper endoscopy was 38.10 for NDBE, 36.63 for IND, 22.63 for LGD, and 11.90 for HGD. Upper endoscopy utilization increased from GERD to BE to BERN, and time between upper endoscopies decreased as the disease stage progressed from BE to BERN, with less frequent utilization in BERN than what would be expected from guideline recommendations for surveillance.

Gaps in hepatocellular carcinoma surveillance in a United States cohort of insured patients with cirrhosis.

OBJECTIVE: Surveillance for hepatocellular carcinoma (HCC) is known to be underutilized; however, neither the variation of surveillance adherence by cirrhosis etiology nor the patient-side economic burden of surveillance are well understood. To identify potential barriers to HCC surveillance, we assessed utilization patterns and costs among US patients with cirrhosis monitored in routine clinical practice. METHODS: We conducted a retrospective study of insured adult patients with cirrhosis using national administrative claims data from January 2013 through June 2019. Time up-to-date with recommended surveillance, correlates of surveillance receipt, and surveillance-associated costs were assessed during a ≥ 6-month follow-up. RESULTS: Among 15,543 patients with cirrhosis (mean [SD] age 64.0 [11.1] years, 50.7% male), 45.8% and 58.7% had received any abdominal imaging at 6 and 12 months, respectively. Patients were up-to-date with recommended surveillance for only 31% of a median 1.3-year follow-up. Those with viral hepatitis were more likely to receive surveillance than those with other etiologies (hazard ratio [HR] 1.55, 95% CI 1.11-2.17, p = .010 for patients without a baseline gastroenterologist [GI] visit and 2.69, 95% CI 1.77-4.09, p < .001 for patients with a GI visit, relative to those with nonalcoholic fatty liver disease and no GI visit). For all etiologies except NAFLD, the HR (95% CI) for surveillance receipt was higher among patients with vs without a baseline GI visit (alcohol-related, 1.164 [1.002-1.351] vs 0.880 [0.796-0.972]; viral hepatitis, 2.688 [1.765-4.093] vs 1.553 [1.111-2.171]; Other, 0.612 [0.519-0.722] vs 0.549 [0.470-0.641]). Mean total and patient-paid daily surveillance-related costs ranged from $540 and $113, respectively (ultrasound) to $1580 and $300, respectively (magnetic resonance imaging), and mean estimated patient productivity costs were $730-$2514 annually. CONCLUSION: HCC surveillance was underutilized and was lowest among patients with nonviral etiologies and those who had not seen a gastroenterologist. Surveillance-related out-of-pocket expenses and lost productivity were substantial. The development of surveillance strategies that reduce patient burden, such as those using blood-based biomarkers, may help improve surveillance adherence and effectiveness.

Gaps in hepatocellular carcinoma surveillance among insured patients with hepatitis B infection without cirrhosis in the United States.

Suboptimal adherence to guidelines for hepatocellular carcinoma (HCC) surveillance among high-risk patients is a persistent problem with substantial detriment to patient outcomes. While patients cite cost as a barrier to surveillance receipt, the financial burden they experience due to surveillance has not been examined. We conducted a retrospective administrative claims study to assess HCC surveillance use and associated costs in a US cohort of insured patients without cirrhosis but with hepatitis B virus (HBV) infection, monitored in routine clinical practice. Of 6831 patients (1122 on antiviral treatment, 5709 untreated), only 39.3% and 51.3% had received any abdominal imaging after 6 and 12 months, respectively, and patients were up to date with HCC surveillance guidelines for only 28% of the follow-up time. Completion of surveillance was substantially higher at 6 and 12 months among treated patients (51.7% and 69.6%, respectively) compared with untreated patients (36.9% and 47.6%, respectively) (p < 0.001). In adjusted models, treated patients were more likely than untreated patients to receive surveillance (hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.53-2.01, p < 0.001), and the proportion of those up to date with surveillance was 9.7% higher (95% CI 6.26-13.07, p < 0.001). Mean total and patient-paid daily surveillance-related costs ranged from $99 (ultrasound) to $334 (magnetic resonance imaging), and mean annual patient costs due to lost productivity for surveillance-related outpatient visits ranged from $93 (using the federal minimum wage) to $321 (using the Bureau of Labor Statistics wage). Conclusion: Use of current HCC surveillance strategies was low across patients with HBV infection, and surveillance was associated with substantial patient financial burden. These data highlight an urgent need for accessible and easy-to-implement surveillance strategies with sufficient sensitivity and specificity for early HCC detection.

Comparison of a multitarget blood test to ultrasound and alpha-fetoprotein for hepatocellular carcinoma surveillance: Results of a network meta-analysis.

Ultrasound-based surveillance has suboptimal sensitivity for early detection of hepatocellular carcinoma (HCC) in patients with cirrhosis. There are several emerging alternatives, including a novel multitarget HCC blood test (Mt-HBT). We compared performance of mt-HBT against ultrasound with or without alpha-fetoprotein (AFP) for early HCC detection in patients with cirrhosis. Per the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, two reviewers searched PubMed, Cochrane, Embase, and clinicaltrials.gov databases from January 1990 through December 2020 to identify studies reporting sensitivity and/or specificity of ultrasound and AFP for overall and early stage HCC detection in patients with cirrhosis. Mt-HBT diagnostic performance was derived from a clinical validation study. A network meta-analysis model was built for comparative assessment, and pooled estimates of sensitivity at a fixed specificity were estimated based on Bayesian binormal receiver operating characteristic models for each modality. Forty-one studies (comprising 62,517 patients with cirrhosis) met inclusion criteria. Ultrasound-alone sensitivity was 51.6% (95% credible interval [CrI], 43.3%-60.5%) for early stage HCC detection, which increased with the addition of AFP to 74.1% (95% CrI, 62.6%-82.4%); however, this was offset by decreased specificity (87.9% vs. 83.9%, respectively). With specificity fixed at 90%, mt-HBT sensitivity for early stage HCC detection was higher than ultrasound alone (18.2%; 95% CrI, 0.2%-37.7%) and similar to ultrasound with AFP (-3.3%; 95% CrI, -22.3%-17.4%). Pairwise posterior probabilities suggested a preference for mt-HBT over ultrasound alone in 97.4% of cases but only 36.3% of cases versus ultrasound with AFP. Conclusion: A blood-based mt-HBT has higher sensitivity than ultrasound alone for early stage HCC detection but similar sensitivity compared to ultrasound and AFP. Mt-HBT could be a comparable alternative to existing methods for HCC surveillance in patients who are at risk.

Cost-Effectiveness of Waiving Coinsurance for Follow-Up Colonoscopy after a Positive Stool-Based Colorectal Screening Test in a Medicare Population.

Commercial insurance covers a follow-up colonoscopy after a positive colorectal cancer-screening test with no patient cost-sharing. Instituting a similar policy for Medicare beneficiaries may increase screening adherence and improve outcomes. The cost-effectiveness of stool-based colorectal cancer screening was compared across adherence scenarios that assumed Medicare coinsurance status quo (20% for follow-up colonoscopy) or waived coinsurance. The CRC-AIM model simulated previously unscreened eligible Medicare beneficiaries undergoing stool-based colorectal cancer screening at age 65 for 10 years. Medicare costs, colorectal cancer cases, colorectal cancer-related deaths, life-years gained (LYG), and quality-adjusted life-years (QALY) were estimated versus no screening. Scenario 1 (S1) assumed 20% coinsurance for follow-up colonoscopy. Scenario 2 (S2) assumed waived coinsurance without adherence changes. Scenarios 3-7 (S3-S7) assumed that waiving coinsurance increased real-world stool-based screening and/or follow-up colonoscopy adherence by 5% or 10%. Sensitivity analyses assumed 1%-4% increased adherence. Cost-effectiveness threshold was ≤$100,000/QALY. Waiving coinsurance without adherence changes (S2) did not affect outcomes versus S1. S3-S7 versus S1 over 10 years estimated up to 3.6 fewer colorectal cancer cases/1,000 individuals, up to 2.1 fewer colorectal cancer deaths, up to 20.7 more LYG, and had comparable total costs per-patient (≤$6,478 vs. $6,449, respectively) as reduced colorectal cancer medical costs offset increased screening and colonoscopy costs. In sensitivity analyses, any increase in adherence after waiving coinsurance was cost-effective and increased LYG. In simulated Medicare beneficiaries, waiving coinsurance for follow-up colonoscopy after a positive stool-based test improved outcomes and was cost-effective when assumed to modestly increase colorectal cancer screening and/or follow-up colonoscopy adherence. PREVENTION RELEVANCE: Follow-up colonoscopy after a positive stool-based test is necessary to complete the colorectal cancer-screening process. This analysis demonstrated that in a simulated Medicare population, waiving coinsurance for a follow-up colonoscopy improved estimated outcomes and was cost-effective when it was assumed that waiving the coinsurance modestly increased screening adherence. See related Spotlight, p. 641.

Adherence to fecal immunochemical test screening among adults at average risk for colorectal cancer.

PURPOSE: This study examined adherence to screening for fecal immunochemical test (FIT). METHODS: Adults (≥ 50-75) with a FIT between 1/1/2014 and 6/30/2019 in MarketScan administrative claims were selected (index = earliest FIT). Patients were followed for 10 years pre- and 3 years post-index. Patients at increased risk for CRC or with prior screening were excluded. Year over year adherence was measured post-index. RESULTS: Of 10,253 patients, the proportion adherent to repeat testing at year 2 was 23.4% and 10.6% at year 3. Of 76.6% not adherent in year 2, 5.4% were adherent in year 3. CONCLUSION: Results suggest adherence to FIT tests is poor, minimizing potential benefits. Future studies are needed to consider alternative test options and whether more choice will improve long-term adherence.

Cross-sectional adherence with the multi-target stool DNA test for colorectal cancer screening in a large, nationally insured cohort.

PURPOSE: Colorectal cancer (CRC) is the second most deadly cancer in the USA. Early detection can improve CRC outcomes, but recent national screening rates (62%) remain below the 80% goal set by the National Colorectal Cancer Roundtable. Multiple options are endorsed for average-risk CRC screening, including the multi-target stool DNA (mt-sDNA) test. We evaluated cross-sectional mt-sDNA test completion in a population of commercially and Medicare-insured patients. METHODS: Participants included individuals ages 50 years and older with commercial insurance or Medicare, with a valid mt-sDNA test shipped by Exact Sciences Laboratories LLC between January 1, 2018, and December 31, 2018 (n = 1,420,460). In 2020, we analyzed cross-sectional adherence, as the percent of successfully completed tests within 365 days of shipment date. RESULTS: Overall cross-sectional adherence was 66.8%. Adherence was 72.1% in participants with Traditional Medicare, 69.1% in participants with Medicare Advantage, and 61.9% in participants with commercial insurance. Adherence increased with age: 60.8% for ages 50-64, 71.3% for ages 65-75, and 74.7% for ages 76 + years. Participants with mt-sDNA tests ordered by gastroenterologists had a higher adherence rate (78.3%) than those with orders by primary care clinicians (67.2%). Geographically, adherence rates were highest among highly rural patients (70.8%) and ordering providers in the Pacific region (71.4%). CONCLUSIONS: Data from this large, national sample of insured patients demonstrate high cross-sectional adherence with the mt-sDNA test, supporting its role as an accepted, noninvasive option for average-risk CRC screening. Attributes of mt-sDNA screening, including home-based convenience and accompanying navigation support, likely contributed to high completion rates.

Healthcare resource utilization and costs among nonalcoholic fatty liver disease patients in Germany.

BACKGROUND: Patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are associated with progression to advanced liver diseases that include compensated cirrhosis, decompensated cirrhosis, liver transplantation, and hepatocellular carcinoma (HCC). This study characterized comorbidities, healthcare resource utilization (HRU), and associated costs among NAFLD patients in Germany. METHODS: German healthcare claims data between 2011 and 2016 were analyzed retrospectively. Adult patients diagnosed with NAFLD and/or NASH were categorized as NAFLD, NAFLD non-progressors, compensated cirrhosis, decompensated cirrhosis, liver transplant, or HCC. Within each stage, annual all-cause HRU and costs were measured during the pre- and post-index periods. RESULTS: Among 4,580,434 patients in the database, proportion of NAFLD was 4.7% (n=215,655). Of them, 36.8% were non-progressors, 0.2% compensated cirrhosis, 9.6% decompensated cirrhosis, 0.0005% liver transplant, and 0.2% HCC. Comorbidity rates were significantly higher in compensated cirrhosis, decompensated cirrhosis, and HCC compared with non-progressors (52.07%, 56.46%, 57.58% vs. 27.49% for cardiovascular disease; 77.13%, 76.61%, 83.47% vs. 54.89% for hypertension; 47.20%, 53.81%, 52.89% vs. 35.21% for hyperlipidemia; 49.88%, 36.67%, 48.21% vs. 20.38% for type 2 diabetes mellitus). The mean annual numbers of post-index outpatient visits and inpatient hospitalizations were significantly higher in patients with advanced liver diseases versus non-progressors. Mean annual costs were significantly higher among patients with advanced liver diseases (compensated cirrhosis, €10,291; decompensated cirrhosis, €22,561; liver transplant, €34,089; HCC, €35,910) than non-progressors (€3,818, P<0.001, except liver transplant cohort). This trend remained consistent after adjusting for baseline demographics and comorbidities. CONCLUSIONS: NAFLD patients in Germany are grossly underdiagnosed and exert substantial healthcare resource use and economic burden, particularly those with advanced liver diseases. Optimal strategies for early identification and management are needed to prevent disease progression and limit the rising costs.

Impact of Patient Adherence to Stool-Based Colorectal Cancer Screening and Colonoscopy Following a Positive Test on Clinical Outcomes.

Colorectal cancer-screening models commonly assume 100% adherence, which is inconsistent with real-world experience. The influence of adherence to initial stool-based screening [fecal immunochemical test (FIT), multitarget stool DNA (mt-sDNA)] and follow-up colonoscopy (after a positive stool test) on colorectal cancer outcomes was modeled using the Colorectal Cancer and Adenoma Incidence and Mortality Microsimulation Model. Average-risk individuals without diagnosed colorectal cancer at age 40 undergoing annual FIT or triennial mt-sDNA screening from ages 50 to 75 were simulated. Primary analyses incorporated published mt-sDNA (71%) or FIT (43%) screening adherence, with follow-up colonoscopy adherence ranging from 40% to 100%. Secondary analyses simulated 100% adherence for stool-based screening and colonoscopy follow-up (S1), published adherence for stool-based screening with 100% adherence to colonoscopy follow-up (S2), and published adherence for both stool-based screening and colonoscopy follow-up after positive mt-sDNA (73%) or FIT (47%; S3). Outcomes were life-years gained (LYG) and colorectal cancer incidence and mortality reductions (per 1,000 individuals) versus no screening. Adherence to colonoscopy follow-up after FIT had to be 4%-13% higher than mt-sDNA to reach equivalent LYG. The theoretical S1 favored FIT versus mt-sDNA (LYG 316 vs. 297; colorectal cancer incidence reduction 68% vs. 64%; colorectal cancer mortality reduction 76% vs. 72%). The more realistic S2 and S3 favored mt-sDNA versus FIT (S2: LYG 284 vs. 245, colorectal cancer incidence reduction 61% vs. 50%, colorectal cancer mortality reduction 69% vs. 59%; S3: LYG 203 vs. 113, colorectal cancer incidence reduction 43% vs. 23%, colorectal cancer mortality reduction 49% vs. 27%, respectively). Incorporating realistic adherence rates for colorectal cancer screening influences modeled outcomes and should be considered when assessing comparative effectiveness. PREVENTION RELEVANCE: Adherence rates for initial colorectal cancer screening by FIT or mt-sDNA and for colonoscopy follow-up of a positive initial test influence the comparative effectiveness of these screening strategies. Using adherence rates based on published data for stool-based testing and colonoscopy follow-up yielded superior outcomes with an mt-sDNA versus FIT-screening strategy.

Lowering the colorectal cancer screening age improves predicted outcomes in a microsimulation model.

AIMS: While most guidelines still recommend colorectal cancer (CRC) screening initiation at age 50 years in average-risk individuals, guideline-creating bodies are starting to lower the recommended age of initiation to 45 years to mitigate the trend of increasing CRC rates in younger populations. Using CRC-AIM, we modeled the impact of lowering the CRC screening initiation age, incorporating theoretical and reported adherence rates, for triennial multi-target stool DNA (mt-sDNA) or annual fecal immunochemical test (FIT) screening. METHODS AND MATERIALS: Screening strategies were simulated for individuals without CRC at age 40 and screened from ages 50 to 75 or 45 to 75 years. Outcomes included CRC incidence, CRC mortality, and life-years gained (LYG) per 1000 individuals screened (compared with no screening). Models used theoretically perfect (100%) and previously reported (71% mt-sDNA; 43% FIT) adherence rates. RESULTS: With perfect adherence, mt-sDNA and FIT resulted in 22.2 and 23.4 more predicted LYG, respectively, with screening initiation at age 45 versus 50 years; reported adherence resulted in 23.9 and 24.4 more LYG, respectively. With perfect adherence, screening initiation at age 45 versus 50 years resulted in 26.1 and 28.6 CRC cases, respectively, with mt-sDNA and 22.8 and 25.5 cases with FIT; with reported real-world adherence there were 28.5 and 31.2 cases, respectively, with mt-sDNA and 37.1 and 40.2 cases with FIT. Similar patterns were observed for CRC deaths. With screening initiation at age 45 and reported adherence, mt-sDNA averted 8.6 more CRC cases and 3.3 more deaths per 1000 individuals than FIT. CONCLUSIONS: Estimated CRC screening outcomes improved by lowering the initiation age from 50 to 45 years. Incorporating reported adherence rates yields greater benefits from triennial mt-sDNA versus annual FIT screening.

Recent trends in colorectal cancer screening methods based on Medicare claims data.

OBJECTIVE: Despite the availability of multiple screening modalities for early detection of colorectal cancer (CRC), participation rates remain well below guideline recommendation goals in the United States. This study analyzed and compared recent national trends in utilization of CRC screening modalities using Medicare claims data. METHOD: Medicare claims data for CRC screening during 2014-2018 were aggregated and analyzed by CPT code frequency. Changes in CRC screening test frequencies during the analysis period were measured via generalized linear models and analysis of compound annual growth rates (CAGRs). RESULTS: Utilization of the mt-sDNA test increased significantly over time (from 2481 claims in 2014 to 335,455 claims in 2018; p < .001), in contrast to the other analyzed CRC screening tests. The CAGR was higher for mt-sDNA (166.81%) than for COL (0.52%), FOBT (-11.75%), and FIT (0.67%). CONCLUSIONS: Utilization of the mt-sDNA test for average-risk CRC screening has increased rapidly since its approval in 2014. These data support growing patient and provider interest in the mt-sDNA test as a non-invasive option for average-risk CRC screening.

Real-world Comorbidity Burden, Health Care Utilization, and Costs of Nonalcoholic Steatohepatitis Patients With Advanced Liver Diseases.

GOALS: This study evaluates the real-world comorbidity burden, health care resource utilization (HRU), and costs among nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) patients with advanced liver diseases [compensated cirrhosis (CC), decompensated cirrhosis (DCC), liver transplantation (LT), hepatocellular carcinoma (HCC)]. BACKGROUND: NAFLD/NASH is a leading cause of liver diseases. MATERIALS AND METHODS: Adult NAFLD/NASH patients were identified retrospectively from MarketScan Commercial claims (2006-2016). Following initial NAFLD/NASH diagnosis, advanced liver diseases were identified using the first diagnosis as their index date. Mean annual all-cause HRU and costs (2016 USD) were reported. Adjusted costs were estimated through generalized linear models. Cumulative costs were illustrated for patient subsets with variable follow-up for each stage. RESULTS: Within the database, 485,774 NAFLD/NASH patients met eligibility criteria. Of these, 93.4% (453,564) were NAFLD/NASH patients without advanced liver diseases, 1.6% (7665) with CC, 3.3% (15,833) with DCC, 0.1% (696) with LT, and 0.1% (428) with HCC. Comorbidity burden was high and increased as patients progressed through liver disease severity stages. Compared with NAFLD/NASH without advanced liver diseases (adjusted costs: $23,860), the annual cost of CC, DCC, LT, and HCC were 1.22, 5.64, 8.27, and 4.09 times higher [adjusted costs: $29,078, $134,448, $197,392, and $97,563 (P<0.0001)]. Inpatient admissions significantly drove increasing HRU. CONCLUSION: Study findings suggest the need for early identification and effective management of NAFLD/NASH patients to minimize comorbidity burden, HRU, and costs in the privately insured US population.

Impact of screening and follow-up colonoscopy adenoma sensitivity on colorectal cancer screening outcomes in the CRC-AIM microsimulation model.

BACKGROUND: Real-world data for patients with positive colorectal cancer (CRC) screening stool-tests demonstrate 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. METHODS: Modeled screening strategies included colonoscopy every 10 years, triennial multitarget stool DNA (mt-sDNA), or annual fecal immunochemical test (FIT) from 50 to 75 years. Outcomes were reported per 1000 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. RESULTS: As 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. CONCLUSIONS: Assuming identical adenoma sensitivities for screening and follow-up/surveillance colonoscopies underestimate the potential benefits of stool-based screening strategies.