Fendrick, A. Mark

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.

10580 Background: Blood-based tests are an emerging option for non-invasive colorectal cancer (CRC) screening for which the Centers for Medicare & Medicaid Services (CMS) has proposed coverage every 3 years for average-risk individuals. Analyses with the CRC-AIM microsimulation model demonstrated that triennial screening with blood-based tests with CMS minimum performance often yields inferior outcomes to stool-based CRC screening (fecal immunochemical test [FIT] and multi-target stool DNA [mt-sDNA]). CRC-AIM was used to explore the impact of blood-based screening intervals, using reported performance characteristics from the ECLIPSE study (Guardant Health, Inc.)1, on estimated clinical outcomes vs FIT and mt-sDNA screening. Methods: Outcomes were simulated for average-risk individuals screened between ages 45-75 years. Intervals were set at 1, 2, or 3 years for blood-based, 3 years for mt-sDNA and annually for FIT screening. The blood-based test was modeled at 83% CRC sensitivity, 13% advanced adenoma sensitivity, and 90% specificity. Perfect adherence (100%) was modeled for blood-based tests and real-world adherence rates used for CRC initial screening tests (mt-sDNA=65.6%; FIT=42.6%) and follow-up colonoscopy (mt-sDNA=72.1%; FIT=46.0%). Primary outcomes were life-years gained (LYG) and colonoscopies (COL) per 1000 individuals for blood-based screening compared to mt-sDNA and FIT. As a secondary analysis, estimates were generated with perfect (100%) adherence assumed for initial screening and follow-up colonoscopy for mt-sDNA and FIT as well. Results: Blood-based testing at a 3-year interval with 100% adherence led to 11% fewer LYG than mt-sDNA at RWE adherence (240 vs 270, respectively), and 9% more COL (1402/1000 vs 1288/1000). Meanwhile, blood-based testing at a 1-year interval and perfect adherence (best case scenario) resulted in the lowest LYG per COL ratio across all scenarios (16% more LYG and 87% more COL compared to mt-sDNA at RWE adherence). Blood-based test results showed similar trends when compared to FIT. Conclusions: Outcomes for blood-based screening every 3 years based on reported test performance characteristics and unrealistic perfect adherence demonstrate fewer LYG as compared to either mt-sDNA or FIT. When compared to real-world adherence for mt-sDNA and FIT, blood-based tests with 1- and 2-year intervals and perfect adherence had higher LYG with the tradeoff of a greater number of diagnostic colonoscopies. [Table: see text]

e18911 Background: Stool-based colorectal cancer (CRC) screening with the multi-target stool DNA (mt-sDNA) test is a guideline endorsed strategy for average-risk individuals age ≥45 years and provides a reference for value-based pricing (VBP); maximum price at which a willingness-to-pay threshold is reached. Blood-based tests (BT) are an emerging screening option. Using recent reported BT performance data from the ECLIPSE study (Guardant Health, Inc.)1, the potential VBP of BT compared with multi-target stool DNA (mt-sDNA) was analyzed. Methods: Using the validated CRC-AIM model, we simulated a cohort of 2 million average-risk individuals who received screening with BT at 1, 2, or 3-year intervals or triennial mt-sDNA between the ages of 45-75 years. For BT, CRC sensitivity, advanced adenoma sensitivity, and specificity were based on reported clinical trial data (83%, 13%, and 90%, respectively). Adherence assumptions for BT and mt-sDNA screening were modeled at perfect (100%) or real-world mt-sDNA adherence (RWE). Key outcomes were life-years gained (LYG) per 1000 individuals vs no screening, and VBP of BT vs mt-sDNA ($895 vs $508) was assessed at a willingness-to-pay (WTP) threshold of $50,000 per quality-adjusted life-year. Results: The triennial mt-sDNA was more effective and less costly vs BT at all intervals with both perfect and RWE adherence at the current price. Compared with mt-sDNA screening, LYG of screening with BT was lower (320 vs. 241-314) and the VBP should be at most $49 and $11 and no-cost at the 1-, 2-, and 3-year intervals, respectively (Table), when perfect adherence is assumed. With RWE adherence, the LYG with mt-sDNA was 306 compared to 229-284 with BT across all intervals. To be comparable to RWE triennial mt-sDNA screening, the maximum VBP for BT would need to be $13 at the 1-year interval and no cost for 2- and 3-year interval. Conclusions: Compared to annual, biannual, and triennial BT, triennial mt-sDNA was more effective at all intervals and 44% to 102% less costly. The maximum price of BT should not exceed $49 to be considered a cost-effective option compared to mt-sDNA when WTP is 50,000. [Table: see text]

6642 Background: Although follow up colonoscopy (COL) after a positive stool-based colorectal cancer (CRC) screening test is necessary to complete the CRC screening process, follow-up COL rates remain suboptimal, especially among underserved populations. As of January 2023, federal policies require commercial insurers and Medicare to eliminate out of pocket costs for follow-up COL. To estimate the implications of this policy change, we compared the clinical and fiscal outcomes for a simulated cohort receiving a follow-up COL after a non-invasive CRC test ($0 cost sharing), compared to the same cohort not completing follow-up COL (status quo). Methods: Using the validated CRC-AIM model, we simulated a cohort of 6 million average-risk individuals who received mt-sDNA (commercial patients at age 45 and Medicare patients at age 65) and further analyzed only the population with positive mt-sDNA. Life-years gained, CRC incidence, CRC-related mortality and total costs of care (inclusive of CRC screening and treatment) were calculated for a cohort that underwent follow-up COL and compared these outcomes to that same cohort that did not complete follow-up COL. The cost of follow-up COL was assumed to be $1,576 for Medicare and $3,086 for commercially insured patients ($0 out of pocket costs for all). Results: Patients undergoing follow-up COL after a positive mt-sDNA experienced more life-years (83 per 1,000 commercially insured patients and 80 per 1,000 Medicare beneficiaries) compared to those who did not undergo follow-up COL. The follow-up COL resulted in reductions in CRC incidence and CRC mortality by 14% and 16% for commercial and 19% and 23% for Medicare beneficiaries, respectively. Compared to those patients with a mt-sDNA positive test result and did not complete follow-up COL, the total cost per patient for those receiving follow-up COL was $3,339 less for commercially insured ($15,690 – no follow up vs. $12,351 – follow up) and $4,382 less for Medicare beneficiaries ($19,337 – no follow up vs. $14,955 – follow up). Total spending for patients receiving follow-up COL was cost-saving when compared to no follow-up as long as the COL costs were less than $6,269 for commercial plans and $5,753 for Medicare. Conclusions: Completing a follow-up COL after a positive mt-sDNA screening saves lives, enhances equity, and lowers total expenditures. Thus, health care stakeholders should invest in efforts to identify and reduce barriers that ultimately lead to an increase uptake of this potentially lifesaving and cost-reducing intervention.

Abstract 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

10529 Background: The Centers for Medicare & Medicaid Services (CMS) recommends covering blood-based biomarker tests with proposed minimum performance thresholds for colorectal cancer (CRC) screening test every 3 years for average-risk, asymptomatic Medicare beneficiaries ages 50–85 years. A blood-based test is a non-invasive screening method to detect CRC but is limited by low sensitivity to detect adenomas. Using the CRC-AIM microsimulation model, predicted life-years gained (LYG) and CRC incidence and mortality reduction were compared between a blood-based test meeting the CMS minimum thresholds and stool-based screening tests (fecal immunochemical test [FIT], fecal occult blood test [FOBT], and multitarget stool DNA [mt-sDNA]). Methods: Outcomes of blood- and stool-based tests were simulated for average-risk individuals free of diagnosed CRC at age 40 and screened between ages 45–75 years per USPSTF recommendations. Per CMS proposed criteria, CRC sensitivity and specificity for a blood-based test were set at 74% and 90%, respectively, and adenoma sensitivity was set at 10%. Published adenoma and CRC sensitivity and specificity were used for each stool test. For the primary analysis, adherence was assumed to be 100%. For secondary analysis, adherence was set at 30–70%, in 10% increments. Outcomes were per 1000 individuals. Results: At 100% adherence, LYG was 229 for a blood test and ≥305 for stool tests, corresponding to at least 25% lower LYG for a blood test relative to all stool tests (Table). Absolute CRC incidence and mortality reductions were at least 19% and 18% lower, respectively, for a blood test vs all stool tests. Secondary analysis indicates that at identical adherence rates that are less than 100%, a blood test had lower LYG vs all stool tests (Table). When the adherence of any test was 50%–70%, a blood test resulted in at least 20% lower LYG vs any stool test, and absolute reductions in CRC incidence and mortality were at least 9% and 10% lower, respectively, vs any stool test. Conclusions: This model suggests that if blood-based CRC screening tests do not sufficiently detect advanced adenomas, clinical outcomes will be inferior to stool-based testing due to lack of cancer prevention. Further discovery efforts to identify blood-based markers associated with both invasive and preinvasive neoplasia are needed to address this deficiency. [Table: see text]

e13624 Background: Commercial insurance plans are required to cover, with no patient cost sharing, a follow-up colonoscopy (COL) after a positive stool-based colorectal cancer (CRC) screening test. Medicare beneficiaries may still be responsible for 20% coinsurance for a follow-up COL, posing a financial barrier to screening completion. Removing the coinsurance may increase screening adherence and improve outcomes. The estimated cost-effectiveness of stool-based CRC screening was compared among adherence scenarios that assumed the status quo (20% coinsurance for follow-up COL) or waived follow-up COL coinsurance. Methods: The CRC-AIM microsimulation model simulated US Medicare beneficiaries undergoing stool-based CRC screening between ages 65-75 years. Outcomes of total costs, total quality adjusted life years (QALYs), life-years gained (LYG), CRC incidence reductions (IR), and CRC mortality reductions (MR) were calculated per 1000 individuals versus no screening using the weighted average of the outcome with multitarget stool DNA, fecal immunochemical test, and fecal occult blood test, scaled by their estimated use. Costs of follow-up COL were assumed to have 20% coinsurance in the status quo scenario. Four comparative scenarios assumed that waiving coinsurance increased published, real-world stool-based screening or follow-up COL adherence rates by 5% or 10%. Results: In scenarios where waiving coinsurance was assumed to increase screening and/or follow-up COL adherence, up to 21 more LYG and greater IR and MR were observed vs the status quo (Table). Total costs in waived coinsurance scenarios (≥$6,398) were comparable to the status quo ($6,449) as the cost savings in CRC care offset the increased COL costs. Total QALYs in waived coinsurance scenarios (≥9.3671) were greater than the status quo (9.3643) because of improved clinical outcomes. Stool-based testing in waived coinsurance scenarios was either dominant (more effective and less costly) or cost-effective at $50,000/QALY with minimal incremental costs vs the status quo. Conclusions: In a simulated Medicare population, clinical CRC outcomes improved and stool-based screening was cost-effective or cost-saving when waiving the 20% coinsurance was assumed to modestly (5%) increase adherence rates for total CRC screening and/or a COL following a positive test. [Table: see text]

Outreach, including patient navigation, has been shown to increase the uptake of colorectal cancer (CRC) screening in underserved populations. This analysis evaluates the cost-effectiveness of triennial multi-target stool DNA (mt-sDNA) versus outreach, with or without a mailed annual fecal immunochemical test (FIT), in a Medicaid population. A microsimulation model estimated the incremental cost-effectiveness ratio using quality-adjusted life years (QALY), direct costs, and clinical outcomes in a cohort of Medicaid beneficiaries aged 50–64 years, over a lifetime time horizon. The base case model explored scenarios of either 100% adherence or real-world reported adherence (51.3% for mt-sDNA, 21.1% for outreach with FIT and 12.3% for outreach without FIT) with or without real-world adherence for follow-up colonoscopy (66.7% for all). Costs and outcomes were discounted at 3.0%. At 100% adherence to both screening tests and follow-up colonoscopy, mt-sDNA costed more and was less effective compared with outreach with or without FIT. When real-world adherence rates were considered for screening strategies (with 100% adherence for follow-up colonoscopy), mt-sDNA resulted in the greatest reduction in incidence and mortality from CRC (41.5% and 45.8%, respectively) compared with outreach with or without FIT; mt-sDNA also was cost-effective versus outreach with and without FIT ($32,150/QALY and $22,707/QALY, respectively). mt-sDNA remained cost-effective versus FIT, with or without outreach, under real-world adherence rates for follow-up colonoscopy. Outreach or navigation interventions, with associated real-world adherence rates to screening tests, should be considered when evaluating the cost-effectiveness of CRC screening strategies in underserved populations.