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.

Estimated Average-Risk Colorectal Cancer Screening-Eligible Population in the US.

This cross-sectional study estimates the number of average-risk colorectal cancer screening­eligible individuals in the US since the US Preventive Services Task Force updated its recommendations in 2021.

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.

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.

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.

Trends in Thyroid Surgery and Guideline-Concordant Care in the United States, 2007-2018.

Background: The American Thyroid Association (ATA) published the 2015 Management Guidelines for patients with thyroid nodules and differentiated thyroid cancer, recommending a shift to less aggressive diagnostic, surgical, and postoperative treatment strategies. At the same time and perhaps related to the new guidelines, there has been a shift to outpatient thyroid surgery. The aim of the current study was to assess physician adherence to these recommendations by identifying and quantifying temporal trends in the rates and indications for thyroid procedures in the inpatient and outpatient settings. Methods: Using the IBM® MarketScan® Commercial database, we identified employer-insured patients in the United States who underwent outpatient and inpatient thyroid surgery from 2007 to 2018. Thyroid surgery was classified as total thyroidectomy (TT), thyroid lobectomy (TL), or a completion thyroidectomy. The surgical indication diagnosis was also determined and classified as either benign or malignant thyroid disease. We compared outpatient and inpatient trends in surgery between benign and malignant thyroid disease both before and after the release of the 2015 ATA guidelines. Results: A total of 220,088 patients who underwent thyroid surgery were included in the analysis. Approximately 80% of TLs were performed in the outpatient setting versus 70% of TTs. Longitudinal analysis showed a statistically significant changepoint for TT proportion occurring in November 2015. The proportion of TT as compared with TL decreased from 80% in September 2015 to 39% by December 2018. For thyroid cancer, there is an increasing trend in performing TL over TT, increasing from 17% in 2015 to 28% by the end of 2018. Conclusions: There was a significant changepoint occurring in November 2015 in the operative and management trends for benign and malignant thyroid disease.

Patient and Provider Risk in Managing ST-Elevation Myocardial Infarction During the COVID-19 Pandemic: A Decision Analysis.

BACKGROUND: The optimal treatment strategy for treating ST-segment-elevation myocardial infarction (STEMI) in context of the coronavirus disease 2019 (COVID-19) pandemic is unclear given the potential risk of occupational exposure during primary percutaneous coronary intervention (PPCI). We quantified the impact of different STEMI treatment strategies on patient outcomes and provider risk in context of the COVID-19 pandemic. METHODS: Using a decision-analytic framework, we evaluated the effect of PPCI versus the pharmaco-invasive strategy for managing STEMI on 30-day patient mortality and individual provider infection risk based on presence of cardiogenic shock, suspected coronary territory, and presence of known or presumptive COVID-19 infection. RESULTS: For patients with low suspicion for COVID-19, PPCI had mortality benefit over the pharmaco-invasive strategy, and the risk of cardiac catheterization laboratory provider infection remained very low (<0.25%) across all subgroups. For patients with presumptive COVID-19 with cardiogenic shock, PPCI offered substantial mortality benefit to patients relative to the pharmaco-invasive strategy (7.9% absolute decrease in 30-day mortality), but also greater risk of provider infection (2.3% absolute increase in risk of provider infection). For patients with presumptive COVID-19 with nonanterior STEMI without cardiogenic shock, PPCI offered a 0.4% absolute mortality benefit over the pharmaco-invasive strategy with a 0.2% greater absolute risk of provider infection, and the tradeoff between patient and provider risk with PPCI became more apparent in sensitivity analysis with more severe COVID-19 infections. CONCLUSIONS: Usual care with PPCI remains the appropriate treatment strategy in the majority of cases presenting with STEMI in the setting of the COVID-19 pandemic. However, utilization of a pharmaco-invasive strategy in selected patients with STEMI with presumptive COVID-19 and low likelihood of mortality from STEMI and use of preventive strategies such as preprocedural intubation in high risk patients when PPCI is the preferred strategy may be reasonable to reduce provider risk of COVID-19 infection.

Improving patient timeliness of care through efficient outpatient clinic layout design using data-driven simulation and optimisation.

With greater demand for outpatient services, the importance of patient-centric clinic layout design that improves timeliness of patient care has become more elucidated. In this paper, a novel simulation-optimisation (SO) framework is proposed focusing on the physical and process flows of patients in the design of a paediatric orthopaedic outpatient clinic. A discrete-event simulation model is used to estimate the frequency of movements between clinic units. The resulting information is utilised as input to a mixed integer programming (MIP) model, optimising the clinic layout design. In order to solve the MIP model, Particle Swarm Optimisation (PSO), a metaheuristic approach enhanced with several heuristics is utilised. Finally, the optimisation model outputs are evaluated with the simulation model. The results demonstrate that improvements to the quality of the patient experience can be achieved through incorporating SO methods into the clinic layout design process.

Adoption of New Medical Technologies: The Case of Customized Individually Made Knee Implants.

OBJECTIVES: To investigate the impact of insurance coverage on the adoption of customized individually made (CIM) knee implants and to compare patient outcomes and cost effectiveness of off-the-shelf and CIM implants. METHODS: A system dynamics simulation model was developed to study adoption dynamics of CIM and meet the research objectives. The model reproduced the historical data on primary and revision knee replacement implants obtained from the literature and the Nationwide Inpatient Sample. Then the dynamics of adoption of CIM implants were simulated from 2018 to 2026. The rate of 90-day readmission, 3-year revision surgery, recovery period, time savings in operating rooms, and the associated cost within 3 years of primary knee replacement implants were used as performance metrics. RESULTS: The simulation results indicate that by 2026, an adoption rate of 90% for CIM implants can reduce the number of readmissions and revision surgeries by 62% and 39%, respectively, and can save hospitals and surgeons 6% on procedure time and cut down cumulative healthcare costs by approximately $38 billion. CONCLUSIONS: CIM implants have the potential to deliver high-quality care while decreasing overall healthcare costs, but their adoption requires the expansion of current insurance coverage. This work presents the first systematic study to understand the dynamics of adoption of CIM knee implants and instrumentation. More broadly, the current modeling approach and systems thinking perspective could be used to consider the adoption of any emerging customized therapies for personalized medicine.

Analysis of the effects of EHR implementation on timeliness of care in a dermatology clinic: a simulation study.

Objective: Quantify the downstream impact on patient wait times and overall length of stay due to small increases in encounter times caused by the implementation of a new electronic health record (EHR) system. Methods: A discrete-event simulation model was created to examine the effects of increasing the provider-patient encounter time by 1, 2, 5, or 10 min, due to an increase in in-room documentation as part of an EHR implementation. Simulation parameters were constructed from an analysis of 52 000 visits from a scheduling database and direct observation of 93 randomly selected patients to collect all the steps involved in an outpatient dermatology patient care visit. Results: Analysis of the simulation results demonstrates that for a clinic session with an average booking appointment length of 15 min, the addition of 1, 2, 5, and 10 min for in-room physician documentation with an EHR system would result in a 5.2 (22%), 9.8 (41%), 31.8 (136%), and 87.2 (373%) minute increase in average patient wait time, and a 6.2 (12%), 11.7 (23%), 36.7 (73%), and 96.9 (193%) minute increase in length of stay, respectively. To offset the additional 1, 2, 5, or 10 min, patient volume would need to decrease by 10%, 20%, 40%, and >50%, respectively. Conclusions: Small changes to processes, such as the addition of a few minutes of extra documentation time in the exam room, can cause significant delays in the timeliness of patient care. Simulation models can assist in quantifying the downstream effects and help analyze the impact of these operational changes.

Decreasing patient length of stay via new flexible exam room allocation policies in ambulatory care clinics.

To address prolonged lengths of stay (LOS) in ambulatory care clinics, we analyze the impact of implementing flexible and dynamic policies for assigning exam rooms to providers. In contrast to the traditional approaches of assigning specific rooms to each provider or pooling rooms among all practitioners, we characterize the impact of alternate compromise policies that have not been explored in previous studies. Since ambulatory care patients may encounter multiple different providers in a single visit, room allocation can be determined separately for each encounter accordingly. For the first phase of the visit, conducted by the medical assistant, we define a dynamic room allocation policy that adjusts room assignments based on the current state of the clinic. For the second phase of the visit, conducted by physicians, we define a series of room sharing policies which vary based on two dimensions, the number of shared rooms and the number of physicians sharing each room. Using a discrete event simulation model of an outpatient cardiovascular clinic, we analyze the benefits and costs associated with the proposed room allocation policies. Our findings show that it is not necessary to fully share rooms among providers in order to reduce patient LOS and physician idle time. Instead, most of the benefit of pooling can be achieved by implementation of a compromise room allocation approach, limiting the need for significant organizational changes within the clinic. Also, in order to achieve most of the benefits of room allocation policies, it is necessary to increase flexibility in the two dimensions simultaneously. These findings are shown to be consistent in settings with alternate patient scheduling and distinctions between physicians.