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.

Calibration and Validation of the Colorectal Cancer and Adenoma Incidence and Mortality (CRC-AIM) Microsimulation Model Using Deep Neural Networks.

OBJECTIVES: Machine learning (ML)-based emulators improve the calibration of decision-analytical models, but their performance in complex microsimulation models is yet to be determined. METHODS: We demonstrated the use of an ML-based emulator with the Colorectal Cancer (CRC)-Adenoma Incidence and Mortality (CRC-AIM) model, which includes 23 unknown natural history input parameters to replicate the CRC epidemiology in the United States. We first generated 15,000 input combinations and ran the CRC-AIM model to evaluate CRC incidence, adenoma size distribution, and the percentage of small adenoma detected by colonoscopy. We then used this data set to train several ML algorithms, including deep neural network (DNN), random forest, and several gradient boosting variants (i.e., XGBoost, LightGBM, CatBoost) and compared their performance. We evaluated 10 million potential input combinations using the selected emulator and examined input combinations that best estimated observed calibration targets. Furthermore, we cross-validated outcomes generated by the CRC-AIM model with those made by CISNET models. The calibrated CRC-AIM model was externally validated using the United Kingdom Flexible Sigmoidoscopy Screening Trial (UKFSST). RESULTS: The DNN with proper preprocessing outperformed other tested ML algorithms and successfully predicted all 8 outcomes for different input combinations. It took 473 s for the trained DNN to predict outcomes for 10 million inputs, which would have required 190 CPU-years without our DNN. The overall calibration process took 104 CPU-days, which included building the data set, training, selecting, and hyperparameter tuning of the ML algorithms. While 7 input combinations had acceptable fit to the targets, a combination that best fits all outcomes was selected as the best vector. Almost all of the predictions made by the best vector laid within those from the CISNET models, demonstrating CRC-AIM's cross-model validity. Similarly, CRC-AIM accurately predicted the hazard ratios of CRC incidence and mortality as reported by UKFSST, demonstrating its external validity. Examination of the impact of calibration targets suggested that the selection of the calibration target had a substantial impact on model outcomes in terms of life-year gains with screening. CONCLUSIONS: Emulators such as a DNN that is meticulously selected and trained can substantially reduce the computational burden of calibrating complex microsimulation models. HIGHLIGHTS: Calibrating a microsimulation model, a process to find unobservable parameters so that the model fits observed data, is computationally complex.We used a deep neural network model, a popular machine learning algorithm, to calibrate the Colorectal Cancer Adenoma Incidence and Mortality (CRC-AIM) model.We demonstrated that our approach provides an efficient and accurate method to significantly speed up calibration in microsimulation models.The calibration process successfully provided cross-model validation of CRC-AIM against 3 established CISNET models and also externally validated against a randomized controlled trial.

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.

Cholestatic Pruritus Treatments in Primary Biliary Cholangitis and Primary Sclerosing Cholangitis: A Systematic Literature Review.

BACKGROUND AND AIMS: We conducted a systematic literature review to understand the evidence supporting treatment decisions for cholestatic pruritus associated with primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). METHODS: Studies that enrolled ≥ 75% participants with PBC or PSC and reported ≥ 1 endpoint(s) related to efficacy, safety, health-related quality of life (HRQoL) or other patient-reported outcomes were included. Bias was assessed using the Cochrane risk of bias tool for randomised controlled trials (RCTs) and the Quality of Cohort studies tool for non-RCTs. RESULTS: Thirty-nine publications were identified, covering 42 studies and six treatment classes (including investigational and approved products): anion-exchange resins, antibiotics (rifampicin/derivatives), opiates, selective serotonin reuptake inhibitors, fibrates, ileal bile acid transporter inhibitors and other agents not categorised in these six classes. Across studies, median sample size was small (n = 18), 20 studies were over 20 years old, 25 followed patients for ≤ 6 weeks, only 25 were RCTs. Pruritus was assessed using several different tools, with inconsistencies in their application. Cholestyramine, considered first-line therapy for moderate-severe cholestatic pruritus, was assessed in six studies (two RCTs) including 56 patients with PBC and 2 with PSC, with evidence of efficacy demonstrated in only three studies, among which, two RCTs were assessed as having a high risk of bias. Findings were similar for other drug classes. CONCLUSIONS: There is a lack of consistent and reproducible evidence available on efficacy, impact on HRQoL, and safety of cholestatic pruritus treatments, leaving physicians to rely on clinical experience rather than evidence-based medicine for treatment selection.

Cost-effectiveness of vibegron for the treatment of overactive bladder in the United States.

AIMS: To evaluate the cost-effectiveness of vibegron compared with other oral pharmacologic therapies as treatment for overactive bladder (OAB). METHODS: A semi-Markov model with monthly cycles was developed to support a lifetime horizon of vibegron 75 mg from a US commercial payor or Medicare perspective. The model incorporated efficacy (reductions in daily micturitions and urinary incontinence episodes), adverse events, OAB-related comorbidities, drug-drug interactions, anticholinergic burden, and treatment persistence. Direct costs and quality-adjusted life years (QALY) were accumulated over time. The primary outcome was the cost per QALY incremental cost-effectiveness ratio (ICER). One-way (OWSA) and probabilistic sensitivity analyses (PSA) were performed. RESULTS: For commercial payors, vibegron was cost-effective at a willingness-to-pay (WTP) threshold of $50,000/QALY versus mirabegron 50 mg (ICER, $9,311) and at a WTP threshold of $150,000/QALY versus mirabegron 25 mg (ICER, $141,957) and versus an anticholinergic basket based on market share (ICER, $118,121). For Medicare, vibegron was cost-effective at a WTP threshold of $50,000/QALY versus mirabegron 50 mg (ICER, $12,154) and at a WTP threshold of $100,000/QALY versus mirabegron 25 mg (ICER, $99,150) and versus an anticholinergic market basket (ICER, $60,756). For commercial payors and Medicare, OWSAs for vibegron versus mirabegron indicated cost-effectiveness was most sensitive to vibegron persistence at 1 and 12 months. PSAs indicated that vibegron was cost-effective versus mirabegron 50 mg 98.6% and 100% of the time at $50,000/QALY for commercial payors and Medicare payors, respectively. LIMITATIONS: Due to lack of real-world data available on persistence, vibegron was assumed to have the same persistence as mirabegron 50 mg. Long-term efficacy was assumed to be sustained beyond 52 weeks in the absence of clinical trials longer than 52 weeks. CONCLUSIONS: Vibegron is cost-effective from a commercial payor (WTP threshold $150,000/QALY) and Medicare (WTP threshold $100,000/QALY) perspective when compared with other oral pharmacologic treatments for OAB.

Overactive bladder (OAB) affects more than 30 million adults in the United States. OAB is a condition associated with frequent and sudden urges to urinate. Drugs for treating OAB may improve symptoms for patients. Anticholinergic drugs are one type of drug available for treating OAB. Anticholinergic drugs may cause side effects such as dry mouth and constipation. Newer types of drugs called ß₃-adrenergic receptor agonists are available for treating OAB symptoms. Vibegron is a member of the ß₃-adrenergic receptor agonist class of drugs. Vibegron does not cause the same side effects related to anticholinergic drugs such as dry mouth and constipation. ß₃-adrenergic receptor agonists work well for OAB symptoms but may be more expensive than anticholinergic drugs. It is important to choose drugs that work well and that are a reasonable price. This study assessed if vibegron is cost-effective for people enrolled in US private insurance and Medicare plans. Compared with other common drugs such as anticholinergic drugs for OAB, vibegron is cost-effective for people enrolled in private insurance and Medicare plans. This was in part because vibegron works better for longer and causes fewer adverse effects than other drugs. Vibegron may be considered "good value for money" for patients with OAB.

Budget Impact Analysis of Vibegron for the Treatment of Overactive Bladder in the USA.

BACKGROUND: Overactive bladder (OAB) is associated with considerable clinical and economic burden. Treatment of patients with OAB using anticholinergics is limited by tolerability issues and increased anticholinergic burden, which is associated with increased risk of dementia and falls/fractures. This analysis assessed the budget impact of introducing the ß3-adrenergic agonist vibegron for the treatment of patients with OAB from US commercial payor and Medicare perspectives. METHODS: A budget impact model (BIM) with a 5-year time horizon was developed using a top-down, prevalence-based approach and projected market shares for 1-million-member US commercial and Medicare plans. The BIM included vibegron, mirabegron, and anticholinergics, incorporating changes in clinical outcomes (efficacy, drug-drug interactions, anticholinergic burden (ACB), OAB-related comorbidities, and adverse events (AEs)). Costs per member per month (PMPM) and per treated member per month (PTMPM) were determined. One-way sensitivity analyses quantified the impact of changes in key variables. RESULTS: The introduction of vibegron was associated with a modest increase in PMPM cost over 5 years of $0.12 (range for years 1‒5, $0.01‒$0.26) for commercial payors and $0.24 ($0.01‒$0.52) for Medicare (PTMPM cost: $2.70 ($0.17‒$4.85) and $3.15 ($0.19‒$5.82), respectively). Costs were partially offset by savings related to decreased third-line treatment use, yearly decreases in AE and comorbidity incidence, reduced drug-drug interactions, and reduced ACB associated with vibegron introduction. PMPM costs were most sensitive to vibegron market share assumptions, OAB prevalence, and vibegron persistence at 1 month for private payors and Medicare and additionally vibegron persistence at 12 months for Medicare. CONCLUSIONS: Vibegron may address unmet needs in treating OAB and is a useful addition to health plans while minimizing risks of anticholinergic AEs, ACB, and drug-drug interactions, which may partially offset increased pharmacy costs.

Adults with overactive bladder (OAB) experience frequent and sudden urges to urinate. OAB affects more than 100 million men and women in the USA. In 2020, the projected cost of OAB was $82.6 billion. One of the standard treatments for OAB includes a class of drugs called anticholinergics. Anticholinergic drugs can cause side effects such as dry mouth and constipation. Over time, taking a lot of anticholinergic drugs may lead to increased risk of cognitive impairment or dementia. Vibegron is from a different class of drug for the treatment of OAB known as ß₃-adrenergic receptor agonists. Adding a new drug to the market may have a financial impact on healthcare plans. This study assessed if adding vibegron for treating OAB is affordable in US commercial and Medicare plans. Adding vibegron to a health plan somewhat increased monthly costs over 5 years. For commercial insurance plans, monthly costs over 5 years increased $0.12 per person enrolled in the plan. For Medicare plans, monthly costs over 5 years increased $0.24 per person enrolled in the plan. However, adding vibegron to the market lowered overall costs not directly related to OAB by lowering healthcare costs related to taking a lot of anticholinergic drugs or costs of outpatient visits. Vibegron for treating OAB may be a helpful addition to health plans. Vibegron may reduce some healthcare costs for patients with OAB.

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.