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Background: Blood-based biomarker tests can potentially change the landscape of colorectal cancer (CRC) screening. We characterize the conditions under which blood test screening would be as effective and cost-effective as annual fecal immunochemical testing or decennial colonoscopy., Methods: We used the 3 Cancer Information and Surveillance Modeling Network-Colon models to compare scenarios of no screening, annual fecal immunochemical testing, decennial colonoscopy, and a blood test meeting Centers for Medicare & Medicaid (CMS) coverage criteria (74% CRC sensitivity and 90% specificity). We varied the sensitivity to detect CRC (74%-92%), advanced adenomas (10%-50%), screening interval (1-3 years), and test cost ($25-$500). Primary outcomes included quality-adjusted life-years (QALY) gained from screening and costs for a US average-risk cohort of individuals aged 45 years., Results: Annual fecal immunochemical testing yielded 125-163 QALY gained per 1000 at a cost of $3811-$5384 per person, whereas colonoscopy yielded 132-177 QALY gained at a cost of $5375-$7031 per person. A blood test with 92% CRC sensitivity and 50% advanced adenoma sensitivity yielded 117-162 QALY gained if used every 3 years and 133-173 QALY gained if used every year but would not be cost-effective if priced above $125 per test. If used every 3 years, a $500 blood test only meeting CMS coverage criteria yielded 83-116 QALY gained at a cost of $8559-$9413 per person., Conclusion: Blood tests that only meet CMS coverage requirements should not be recommended to patients who would otherwise undergo screening by colonoscopy or fecal immunochemical testing because of lower benefit. Blood tests need higher advanced adenoma sensitivity (above 40%) and lower costs (below $125) to be cost-effective., (© The Author(s) 2024. Published by Oxford University Press.)

Background & Aims: A blood-based colorectal cancer (CRC) screening test may increase screening participation. However, blood tests may be less effective than current guideline-endorsed options. The Centers for Medicare & Medicaid Services (CMS) covers blood tests with sensitivity of at least 74% for detection of CRC and specificity of at least 90%. In this study, we investigate whether a blood test that meets these criteria is cost-effective., Methods: Three microsimulation models for CRC (MISCAN-Colon, CRC-SPIN, and SimCRC) were used to estimate the effectiveness and cost-effectiveness of triennial blood-based screening (from ages 45 to 75 years) compared to no screening, annual fecal immunochemical testing (FIT), triennial stool DNA testing combined with an FIT assay, and colonoscopy screening every 10 years. The CMS coverage criteria were used as performance characteristics of the hypothetical blood test. We varied screening ages, test performance characteristics, and screening uptake in a sensitivity analysis., Results: Without screening, the models predicted 77-88 CRC cases and 32-36 CRC deaths per 1000 individuals, costing $5.3-$5.8 million. Compared to no screening, blood-based screening was cost-effective, with an additional cost of $25,600-$43,700 per quality-adjusted life-year gained (QALYG). However, compared to FIT, triennial stool DNA testing combined with FIT, and colonoscopy, blood-based screening was not cost-effective, with both a decrease in QALYG and an increase in costs. FIT remained more effective (+5-24 QALYG) and less costly (-$3.2 to -$3.5 million) than blood-based screening even when uptake of blood-based screening was 20 percentage points higher than uptake of FIT., Conclusion: Even with higher screening uptake, triennial blood-based screening, with the CMS-specified minimum performance sensitivity of 74% and specificity of 90%, was not projected to be cost-effective compared with established strategies for colorectal cancer screening., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

During the COVID-19 pandemic, health systems, including federally qualified health centers, experienced disruptions in colorectal cancer (CRC) screening. National organizations called for greater use of at-home stool-based testing followed by colonoscopy for those with abnormal test results to limit (in-person) colonoscopy exams to people with acute symptoms or who were high risk. This stool-test-first strategy may also be useful for adults with low-risk adenomas who are due for surveillance colonoscopy. We argue that colonoscopy is overused as a first-line screening method in low- and average-risk adults and as a surveillance tool among adults with small adenomas. Yet, simultaneously, many people do not receive much-needed colonoscopies. Delivering the right screening tests at intervals that reduce the risk of CRC, while minimizing patient inconvenience and procedural risks, can strengthen health-care systems. Risk stratification could improve efficiency of CRC screening, but because models that adequately predict risk are years away from clinical use, we need to optimize use of currently available technology-that is, low-cost fecal testing followed by colonoscopy for those with abnormal test results. The COVID-19 pandemic highlighted the urgent need to adapt to resource constraints around colonoscopies and showed that increased use of stool-based testing was possible. Learning how to adapt to such constraints without sacrificing patients' health, particularly for patients who receive care at federally qualified health centers, should be a priority for CRC prevention research., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The US Black population has higher colorectal cancer (CRC) incidence rates and worse CRC survival than the US White population, as well as historically lower rates of CRC screening. The Surveillance, Epidemiology, and End Results incidence rate data in people diagnosed between the ages of 20 and 45 years, before routine CRC screening is recommended, were analyzed to estimate temporal changes in CRC risk in Black and White populations. There was a rapid rise in rectal and distal colon cancer incidence in the White population but not the Black population, and little change in proximal colon cancer incidence for both groups. In 2014-2018, CRC incidence per 100 000 was 17.5 (95% confidence interval [CI] = 15.3 to 19.9) among Black individuals aged 40-44 years and 16.6 (95% CI = 15.6 to 17.6) among White individuals aged 40-44 years; 42.3% of CRCs diagnosed in Black patients were proximal colon cancer, and 41.1% of CRCs diagnosed in White patients were rectal cancer. Analyses used a race-specific microsimulation model to project screening benefits, based on life-years gained and lifetime reduction in CRC incidence, assuming these Black-White differences in CRC risk and location. The projected benefits of screening (via either colonoscopy or fecal immunochemical testing) were greater in the Black population, suggesting that observed Black-White differences in CRC incidence are not driven by differences in risk. Projected screening benefits were sensitive to survival assumptions made for Black populations. Building racial disparities in survival into the model reduced projected screening benefits, which can bias policy decisions., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background & Aims: Colorectal cancer (CRC) screening guidelines include screening colonoscopy and sequential high-sensitivity fecal occult blood testing (HSgFOBT), with expectation of similar effectiveness based on the assumption of similar high adherence. However, adherence to screening colonoscopy compared with sequential HSgFOBT has not been reported. In this randomized clinical trial, we assessed adherence and pathology findings for a single screening colonoscopy vs sequential and nonsequential HSgFOBTs., Methods: Participants aged 40-69 years were enrolled at 3 centers representing different clinical settings. Participants were randomized into a single screening colonoscopy arm vs sequential HSgFOBT arm composed of 4-7 rounds. Initial adherence to screening colonoscopy and sequential adherence to HSgFOBT, follow-up colonoscopy for positive HSgFOBT tests, crossover to colonoscopy, and detection of advanced neoplasia or large serrated lesions (ADN-SERs) were measured., Results: There were 3523 participants included in the trial; 1761 and 1762 participants were randomized to the screening colonoscopy and HSgFOBT arms, respectively. Adherence was 1473 (83.6%) for the screening colonoscopy arm vs 1288 (73.1%) for the HSgFOBT arm after 1 round (relative risk [RR], 1.14; 95% CI, 1.10-1.19; P ≤ .001), but only 674 (38.3%) over 4 sequential HSgFOBT rounds (RR, 2.19; 95% CI, 2.05-2.33). Overall adherence to any screening increased to 1558 (88.5%) in the screening colonoscopy arm during the entire study period and 1493 (84.7%) in the HSgFOBT arm (RR, 1.04; 95% CI, 1.02-1.07). Four hundred thirty-six participants (24.7%) crossed over to screening colonoscopy during the first 4 rounds. ADN-SERs were detected in 121 of the 1473 participants (8.2%) in the colonoscopy arm who were adherent to protocol in the first 12 months of the study, whereas detection of ADN-SERs among those who were not sequentially adherent (n = 709) to HSgFOBT was subpar (0.6%) (RR, 14.72; 95% CI, 5.46-39.67) compared with those who were sequentially adherent (3.3%) (n = 647) (RR, 2.52; 95% CI, 1.61-3.98) to HSgFOBT in the first 4 rounds. When including colonoscopies from HSgFOBT patients who were never positive yet crossed over (n = 1483), 5.5% of ADN-SERs were detected (RR, 1.50; 95% CI, 1.15-1.96) in the first 4 rounds., Conclusions: Observed adherence to sequential rounds of HSgFOBT was suboptimal compared with a single screening colonoscopy. Detection of ADN-SERs was inferior when nonsequential HSgFOBT adherence was compared with sequential adherence. However, the greatest number of ADN-SERs was detected among those who crossed over to colonoscopy and opted to receive a colonoscopy. The effectiveness of an HSgFOBT screening program may be enhanced if crossover to screening colonoscopy is permitted., Clinicaltrials: gov, Number: NCT00102011., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

The aftermath of the initial phase of the COVID-19 pandemic may contribute to the widening of disparities in colorectal cancer (CRC) outcomes due to differential disruptions to CRC screening. This comparative microsimulation analysis uses two CISNET CRC models to simulate the impact of ongoing screening disruptions induced by the COVID-19 pandemic on long-term CRC outcomes. We evaluate three channels through which screening was disrupted: delays in screening, regimen switching, and screening discontinuation. The impact of these disruptions on long-term CRC outcomes was measured by the number of life-years lost due to CRC screening disruptions compared to a scenario without any disruptions. While short-term delays in screening of 3-18 months are predicted to result in minor life-years loss, discontinuing screening could result in much more significant reductions in the expected benefits of screening. These results demonstrate that unequal recovery of screening following the pandemic can widen disparities in CRC outcomes and emphasize the importance of ensuring equitable recovery to screening following the pandemic., Competing Interests: PN, Rv, AH, MH, NC, JO, AZ, IL, CR No competing interests declared, (© 2023, Nascimento de Lima et al.)

Colorectal cancer (CRC) incidence rates have decreased among adults aged 50 years or older while increasing in adults under age 50 years. Understanding these trends is challenging because of the multiple related time scales of age, diagnosis period, and birth cohort. We analyzed incidence rates of rectal, distal colon, and proximal colon cancer for individuals aged 20 years or more from the Surveillance, Epidemiology, and End Results Program for diagnosis years 1978-2017. We used a 2-stage generalized linear model to determine age, period, and cohort effects for CRC incidence. We first estimated birth cohort effects among people under age 45 years. We used these results to specify prior distributions for cohort effects in a Bayesian model to estimate period effects among people aged 45 years or more. There was no evidence of period effects for people under age 45 years. Risks of rectal and distal colon cancer increased for later birth cohorts. Compared with the 1943-1952 birth cohort, the 1983-1992 birth cohort had 2.2 times the risk of rectal cancer, 1.9 times the risk of distal colon cancer, and 1.3 times the risk of proximal colon cancer. For people aged ≥45 years, period effects showed declines in CRC risk that were attributable to screening., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Many colorectal cancer-related procedures were suspended during the COVID-19 pandemic. In this study, we predict the impact of resulting delays in screening (colonoscopy, FIT, and sigmoidoscopy) and diagnosis on colorectal cancer-related outcomes, and compare different recovery scenarios., Methods: Using the MISCAN-Colon model, we simulated the US population and evaluated different impact and recovery scenarios. Scenarios were defined by the duration and severity of the disruption (percentage of eligible adults affected), the length of delays, and the duration of the recovery. During recovery (6, 12 or 24 months), capacity was increased to catch up missed procedures. Primary outcomes were excess colorectal cancer cases and -related deaths, and additional colonoscopies required during recovery., Results: With a 24-month recovery, the model predicted that the US population would develop 7,210 (0.18%) excess colorectal cancer cases during 2020-2040, and 6,950 (0.65%) excess colorectal cancer-related deaths, and require 108,500 (8.6%) additional colonoscopies per recovery month, compared with a no-disruption scenario. Shorter recovery periods of 6 and 12 months, respectively, decreased excess colorectal cancer-related deaths to 4,190 (0.39%) and 4,580 (0.43%), at the expense of 260,200-590,100 (20.7%-47.0%) additional colonoscopies per month., Conclusions: The COVID-19 pandemic will likely cause more than 4,000 excess colorectal cancer-related deaths in the US, which could increase to more than 7,000 if recovery periods are longer., Impact: Our results highlight that catching-up colorectal cancer-related services within 12 months provides a good balance between required resources and mitigation of the impact of the disruption on colorectal cancer-related deaths., (©2022 The Authors; Published by the American Association for Cancer Research.)

Although studies have suggested that mindfulness-based interventions might be effective in enhancing military readiness and resilience, this has not been rigorously evaluated. This study presents results from a systematic review and meta-analyses of research examining how mindfulness meditation affects 13 performance-related outcomes of interest to the U.S. Army and broader military. The authors supplemented the systematic review by examining how mindfulness meditation could support stress management and exploring characteristics of selected mindfulness programs. The goal was to develop recommendations for mindfulness meditation programs for soldiers, should the Army choose to implement such programs in the future. Findings suggest that mindfulness may improve some aspects of attention and emotion regulation, impulsivity, and work-related morale and social support. The available evidence does not suggest that mindfulness improves other outcomes of interest to the Army. Notably, mindfulness meditation programs reduce stress and may reduce parental stress, which could benefit Army families. Yet more research is needed to identify best practices for implementing mindfulness programs in the military. The authors recommend conducting high-quality evaluations of mindfulness meditation with soldiers and assessing the effect of mindfulness meditation on military families., (Copyright © 2022 RAND Corporation.)

The coronavirus disease 2019 pandemic required significant public health interventions from local governments. Early in the pandemic, RAND researchers developed a decision support tool to provide policymakers with insight into the trade-offs they might face when choosing among nonpharmaceutical intervention levels. Using an updated version of the model, the researchers performed a stress-test of a variety of alternative reopening plans, using California as an example. This article presents the general lessons learned from these experiments and discusses four characteristics of the best reopening strategies., (Copyright © 2022 RAND Corporation.)

Objective: Annual fecal immunochemical tests can reduce colorectal cancer incidence and mortality. However, screening is a multi-step process and most patients do not perfectly adhere to guideline-recommended screening schedules. Our objective was to compare the reduction in colorectal cancer incidence and life-years gained based on US guideline-concordant fecal immunochemical test screening to scenarios with a range of delays., Method: The Colorectal Cancer Simulated Population model for Incidence and Natural history (CRC-SPIN) microsimulation model was used to estimate the effect of systematic departures from fecal immunochemical test screening guidelines on lifetime screening benefit., Results: The combined effect of consistent modest delays in screening initiation (1 year), repeated fecal immunochemical test screening (3 months), and receipt of follow-up or surveillance colonoscopy (3 months) resulted in up to 1.3 additional colorectal cancer cases per 10,000, 0.4 additional late-stage colorectal cancer cases per 10,000 and 154.7 fewer life-years gained per 10,000. A 5-year delay in screening initiation had a larger impact on screening effectiveness than consistent small delays in repeated fecal immunochemical test screening or receipt of follow-up colonoscopy after an abnormal fecal immunochemical test. The combined effect of consistent large delays in screening initiation (5 years), repeated fecal immunochemical test screening (6 months), and receipt of follow-up or surveillance colonoscopy (6 months) resulted in up to 3.7 additional colorectal cancer cases per 10,000, 1.5 additional late-stage colorectal cancer cases per 10,000 and 612.3 fewer life-years gained per 10,000., Conclusions: Systematic delays across the screening process can result in meaningful reductions in colorectal cancer screening effectiveness, especially for longer delays. Screening delays could drive differences in colorectal cancer incidence across patient groups with differential access to screening.

Background: Models can help guide colorectal cancer screening policy. Although models are carefully calibrated and validated, there is less scrutiny of assumptions about test performance., Methods: We examined the validity of the CRC-SPIN model and colonoscopy sensitivity assumptions. Standard sensitivity assumptions, consistent with published decision analyses, assume sensitivity equal to 0.75 for diminutive adenomas (<6 mm), 0.85 for small adenomas (6-10 mm), 0.95 for large adenomas (≥10 mm), and 0.95 for preclinical cancer. We also selected adenoma sensitivity that resulted in more accurate predictions. Targets were drawn from the Wheat Bran Fiber study. We examined how well the model predicted outcomes measured over a three-year follow-up period, including the number of adenomas detected, the size of the largest adenoma detected, and incident colorectal cancer., Results: Using standard sensitivity assumptions, the model predicted adenoma prevalence that was too low (42.5% versus 48.9% observed, with 95% confidence interval 45.3%-50.7%) and detection of too few large adenomas (5.1% versus 14.% observed, with 95% confidence interval 11.8%-17.4%). Predictions were close to targets when we set sensitivities to 0.20 for diminutive adenomas, 0.60 for small adenomas, 0.80 for 10- to 20-mm adenomas, and 0.98 for adenomas 20 mm and larger., Conclusions: Colonoscopy may be less accurate than currently assumed, especially for diminutive adenomas. Alternatively, the CRC-SPIN model may not accurately simulate onset and progression of adenomas in higher-risk populations., Impact: Misspecification of either colonoscopy sensitivity or disease progression in high-risk populations may affect the predicted effectiveness of colorectal cancer screening. When possible, decision analyses used to inform policy should address these uncertainties.See related commentary by Etzioni and Lange, p. 702., (©2021 American Association for Cancer Research.)

Background: Microsimulation models are mathematical models that simulate event histories for individual members of a population. They are useful for policy decisions because they simulate a large number of individuals from an idealized population, with features that change over time, and the resulting event histories can be summarized to describe key population-level outcomes. Model calibration is the process of incorporating evidence into the model. Calibrated models can be used to make predictions about population trends in disease outcomes and effectiveness of interventions, but calibration can be challenging and computationally expensive., Methods: This paper develops a technique for sequentially updating models to take full advantage of earlier calibration results, to ultimately speed up the calibration process. A Bayesian approach to calibration is used because it combines different sources of evidence and enables uncertainty quantification which is appealing for decision-making. We develop this method in order to re-calibrate a microsimulation model for the natural history of colorectal cancer to include new targets that better inform the time from initiation of preclinical cancer to presentation with clinical cancer (sojourn time), because model exploration and validation revealed that more information was needed on sojourn time, and that the predicted percentage of patients with cancers detected via colonoscopy screening was too low., Results: The sequential approach to calibration was more efficient than recalibrating the model from scratch. Incorporating new information on the percentage of patients with cancers detected upon screening changed the estimated sojourn time parameters significantly, increasing the estimated mean sojourn time for cancers in the colon and rectum, providing results with more validity., Conclusions: A sequential approach to recalibration can be used to efficiently recalibrate a microsimulation model when new information becomes available that requires the original targets to be supplemented with additional targets., (© 2022. The Author(s).)

Background: Dementia is a common disease that has an impact on both the affected individual and family members who provide caregiving. Simulation models can assist in setting policy that anticipates public health needs by predicting the demand for and availability of care., Objective: We developed a relatively simple method for simulating the onset of dementia that can be used in combination with an existing microsimulation model., Methods: We started with Socsim, a demographic microsimulation model that simulates a population with family kinship networks. We simulated dementia in the Socsim population by simulating the number of individuals diagnosed with dementia in their lifetime and the ages of onset and death from dementia for each of these dementia cases. We then matched dementia cases to the simulated population based on age at death, so for each individual, we simulate whether they develop dementia and, if so, their age at onset. This approach simulates dementia onset but does not alter the demographic model's simulated age of death., Results: We selected model dementia parameters so that the combined Socsim-Dementia model reproduces published dementia prevalence rates and survival times after diagnosis., Conclusions: Adding simulation of dementia to a kinship network model enables prediction of the availability of family caregivers for people with dementia under a range of different assumptions about future fertility, mortality, and dementia risk. We demonstrated how to add simulation of dementia onset and death to an existing microsimulation model to obtain a method for predicting dementia prevalence in the context of another more detailed model. The approach we developed can be generalized to simulate other progressive health conditions that affect mortality.

The COVID-19 pandemic required significant public health interventions from local governments. Although nonpharmaceutical interventions often were implemented as decision rules, few studies evaluated the robustness of those reopening plans under a wide range of uncertainties. This paper uses the Robust Decision Making approach to stress-test 78 alternative reopening strategies, using California as an example. This study uniquely considers a wide range of uncertainties and demonstrates that seemingly sensible reopening plans can lead to both unnecessary COVID-19 deaths and days of interventions. We find that plans using fixed COVID-19 case thresholds might be less effective than strategies with time-varying reopening thresholds. While we use California as an example, our results are particularly relevant for jurisdictions where vaccination roll-out has been slower. The approach used in this paper could also prove useful for other public health policy problems in which policymakers need to make robust decisions in the face of deep uncertainty., Competing Interests: P. Nascimento de Lima, R. Lempert, L. Baker, J.S. Ringel, R. Vardavas and C. Rutter are affiliated with the RAND Corporation, a non-profit research organization. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Calibration of a microsimulation model (MSM) is a challenging but crucial step for the development of a valid model. Numerous calibration methods for MSMs have been suggested in the literature, most of which are usually adjusted to the specific needs of the model and based on subjective criteria for the selection of optimal parameter values. This article compares 2 general approaches for calibrating MSMs used in medical decision making, a Bayesian and an empirical approach. We use as a tool the MIcrosimulation Lung Cancer (MILC) model, a streamlined, continuous-time, dynamic MSM that describes the natural history of lung cancer and predicts individual trajectories accounting for age, sex, and smoking habits. We apply both methods to calibrate MILC to observed lung cancer incidence rates from the Surveillance, Epidemiology and End Results (SEER) database. We compare the results from the 2 methods in terms of the resulting parameter distributions, model predictions, and efficiency. Although the empirical method proves more practical, producing similar results with smaller computational effort, the Bayesian method resulted in a calibrated model that produced more accurate outputs for rare events and is based on a well-defined theoretical framework for the evaluation and interpretation of the calibration outcomes. A combination of the 2 approaches is an alternative worth considering for calibrating complex predictive models, such as microsimulation models.

Objective: To identify and suggest strategies to make insufficient evidence ratings in systematic reviews more actionable., Study Design and Setting: A workgroup comprising members from the Evidence-Based Practice (EPC) Program of the Agency for Healthcare Research and Quality convened throughout 2020. We conducted iterative discussions considering information from three data sources: a literature review for relevant publications and frameworks, a review of a convenience sample of past systematic reviews conducted by the EPCs, and an audit of methods used in past EPC technical briefs., Results: We identified five strategies for supplementing systematic review findings when evidence on benefits or harms is expected to be, or found to be, insufficient: 1) reconsider eligible study designs, 2) summarize indirect evidence, 3) summarize contextual and implementation evidence, 4) consider modelling, and 5) incorporate unpublished health system data in the evidence synthesis. While these strategies may not increase the strength of evidence, they may improve the utility of reports for decision makers. Adopting these strategies depends on feasibility, timeline, funding, and expertise of the systematic reviewers., Conclusion: Throughout the process of evidence synthesis of early scoping, protocol development, review conduct, and review presentation, authors can consider these five strategies to supplement evidence with insufficient rating to make it more actionable for end-users., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: The US Preventive Services Task Force (USPSTF) is updating its 2016 colorectal cancer screening recommendations., Objective: To provide updated model-based estimates of the benefits, burden, and harms of colorectal cancer screening strategies and to identify strategies that may provide an efficient balance of life-years gained (LYG) from screening and colonoscopy burden to inform the USPSTF., Design, Setting, and Participants: Comparative modeling study using 3 microsimulation models of colorectal cancer screening in a hypothetical cohort of 40-year-old US individuals at average risk of colorectal cancer., Exposures: Screening from ages 45, 50, or 55 years to ages 70, 75, 80, or 85 years with fecal immunochemical testing (FIT), multitarget stool DNA testing, flexible sigmoidoscopy alone or with FIT, computed tomography colonography, or colonoscopy. All persons with an abnormal noncolonoscopy screening test result were assumed to undergo follow-up colonoscopy. Screening intervals varied by test. Full adherence with all procedures was assumed., Main Outcome and Measures: Estimated LYG relative to no screening (benefit), lifetime number of colonoscopies (burden), number of complications from screening (harms), and balance of incremental burden and benefit (efficiency ratios). Efficient strategies were those estimated to require fewer additional colonoscopies per additional LYG relative to other strategies., Results: Estimated LYG from screening strategies ranged from 171 to 381 per 1000 40-year-olds. Lifetime colonoscopy burden ranged from 624 to 6817 per 1000 individuals, and screening complications ranged from 5 to 22 per 1000 individuals. Among the 49 strategies that were efficient options with all 3 models, 41 specified screening beginning at age 45. No single age to end screening was predominant among the efficient strategies, although the additional LYG from continuing screening after age 75 were generally small. With the exception of a 5-year interval for computed tomography colonography, no screening interval predominated among the efficient strategies for each modality. Among the strategies highlighted in the 2016 USPSTF recommendation, lowering the age to begin screening from 50 to 45 years was estimated to result in 22 to 27 additional LYG, 161 to 784 additional colonoscopies, and 0.1 to 2 additional complications per 1000 persons (ranges are across screening strategies, based on mean estimates across models). Assuming full adherence, screening outcomes and efficient strategies were similar by sex and race and across 3 scenarios for population risk of colorectal cancer., Conclusions and Relevance: This microsimulation modeling analysis suggests that screening for colorectal cancer with stool tests, endoscopic tests, or computed tomography colonography starting at age 45 years provides an efficient balance of colonoscopy burden and life-years gained.

Accurately describing treatment effects using plain language and narrative statements is a critical step in communicating research findings to end users. However, the process of developing these narratives has not been historically guided by a specific framework. The Agency for Healthcare Research and Quality Evidence-based Practice Center Program developed guidance for narrative summaries of treatment effects that identifies five constructs. We explicitly identify these constructs to facilitate developing narrative statements: (1) direction of effect, (2) size of effect, (3) clinical importance, (4) statistical significance, and (5) strength or certainty of evidence. These constructs clearly overlap. It may not always be feasible to address all five constructs. Based on context and intended audience, investigators can determine which constructs will be most important to address in narrative statements.

Racial disparities in colorectal cancer incidence are widely documented. There are two potential mechanisms for these disparities: differences in access to screening, including screening follow-up, and differences in underlying risk of colorectal cancer. We reviewed the literature for evidence of these two mechanisms. We show that higher colorectal cancer incidence in blacks relative to whites emerged only after the dissemination of screening and describe evidence of racial disparities in screening rates. In contrast to the strong evidence for differences in colorectal cancer screening utilization, there is limited evidence for racial differences in adenoma prevalence. In general, black and white patients who are screened have similar adenoma prevalence, though there is some evidence that advanced adenomas and adenomas in the proximal colon are somewhat more likely in black than white patients. We conclude that higher rates of colorectal cancer incidence among black patients are primarily driven by lower rates of colorectal cancer screening. Our findings highlight the need to increase black patients' access to quality screening to reduce colorectal cancer incidence and mortality., (©2020 American Association for Cancer Research.)

Microsimulation models are often used to predict long-term outcomes and guide policy decisions regarding cancer screening. The United Kingdom Flexible Sigmoidoscopy Screening (UKFSS) Trial examines a one-time intervention of flexible sigmoidoscopy that was implemented before a colorectal cancer (CRC) screening program was established. Long-term study outcomes, now a full 17 y following randomization, have been published. We use the outcomes from this trial to validate 3 microsimulation models for CRC to long-term study outcomes. We find that 2 of 3 models accurately predict the relative effect of screening (the hazard ratios) on CRC-specific incidence 17 y after screening. We find that all 3 models yield predictions of the relative effect of screening on CRC incidence and mortality (i.e., the hazard ratios) that are reasonably close to the UKFSS results. Two of the 3 models accurately predict the relative reduction in CRC incidence 17 y after screening. One model accurately predicted the absolute incidence and mortality rates in the screened group. The models differ in their estimates related to adenoma detection at screening. Although high-quality screening results help to inform models, trials are expensive, last many years, and can be complicated by ethical issues and technological changes across the duration of the trial. Thus, well-calibrated and validated models are necessary to predict outcomes for which data are not available. The results from this validation demonstrate the utility of models in predicting long-term outcomes and in collaborative modeling to account for uncertainty.

Background: There is a lack of research on the effectiveness of online peer support groups for reducing social isolation and depressive symptoms among caregivers, and previous research has mixed results., Objective: This study aimed to test whether military caregivers who joined a new online peer support community or engaged with an existing online community experienced decreased perceived social isolation and improved depressive symptoms over 6 months., Methods: We conducted a longitudinal study of 212 military caregivers who had newly joined an online community and those who were members of other military caregiver groups. Multiple indicators of perceived social isolation and depressive symptoms were assessed at baseline and at 3 and 6 months., Results: Compared with caregivers in the comparison group, caregivers who joined the new group experienced less perceived social isolation at 3 months (eg, number of caregivers in social network [unstandardized regression coefficients] b=0.49, SE 0.19, 95% CI 0.87 to 0.02), but this effect did not persist at 6 months. Those who engaged more with new or existing groups experienced less perceived social isolation over time (eg, number of caregivers in social network b=0.18, SE 0.06, 95% CI 0.02 to 0.27), and this relationship was mediated by increased interactions with other military caregivers (95% CI 0.0046 to 0.0961). Engagement with an online group was not associated with improvements in depressive symptoms., Conclusions: Online communities might help reduce social isolation when members engage with the group, but more intensive treatment is needed to improve depressive symptoms., (©Thomas E Trail, Esther Friedman, Carolyn M Rutter, Terri Tanielian. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 23.04.2020.)

Background: Cancer screening is a complex process encompassing risk assessment, the initial screening examination, diagnostic evaluation, and treatment of cancer precursors or early cancers. Metrics that enable comparisons across different screening targets are needed. We present population-based screening metrics for breast, cervical, and colorectal cancers for nine sites participating in the Population-based Research Optimizing Screening through Personalized Regimens consortium., Methods: We describe how selected metrics map to a trans-organ conceptual model of the screening process. For each cancer type, we calculated calendar year 2013 metrics for the screen-eligible target population (breast: ages 40-74 years; cervical: ages 21-64 years; colorectal: ages 50-75 years). Metrics for screening participation, timely diagnostic evaluation, and diagnosed cancers in the screened and total populations are presented for the total eligible population and stratified by age group and cancer type., Results: The overall screening-eligible populations in 2013 were 305 568 participants for breast, 3 160 128 for cervical, and 2 363 922 for colorectal cancer screening. Being up-to-date for testing was common for all three cancer types: breast (63.5%), cervical (84.6%), and colorectal (77.5%). The percentage of abnormal screens ranged from 10.7% for breast, 4.4% for cervical, and 4.5% for colorectal cancer screening. Abnormal breast screens were followed up diagnostically in almost all (96.8%) cases, and cervical and colorectal were similar (76.2% and 76.3%, respectively). Cancer rates per 1000 screens were 5.66, 0.17, and 1.46 for breast, cervical, and colorectal cancer, respectively., Conclusions: Comprehensive assessment of metrics by the Population-based Research Optimizing Screening through Personalized Regimens consortium enabled systematic identification of screening process steps in need of improvement. We encourage widespread use of common metrics to allow interventions to be tested across cancer types and health-care settings., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Microsimulation models (MSMs) are used to inform policy by predicting population-level outcomes under different scenarios. MSMs simulate individual-level event histories that mark the disease process (such as the development of cancer) and the effect of policy actions (such as screening) on these events. MSMs often have many unknown parameters; calibration is the process of searching the parameter space to select parameters that result in accurate MSM prediction of a wide range of targets. We develop Incremental Mixture Approximate Bayesian Computation (IMABC) for MSM calibration, which results in a simulated sample from the posterior distribution of model parameters given calibration targets. IMABC begins with a rejection-based ABC step, drawing a sample of points from the prior distribution of model parameters and accepting points that result in simulated targets that are near observed targets. Next, the sample is iteratively updated by drawing additional points from a mixture of multivariate normal distributions and accepting points that result in accurate predictions. Posterior estimates are obtained by weighting the final set of accepted points to account for the adaptive sampling scheme. We demonstrate IMABC by calibrating CRC-SPIN 2.0, an updated version of a MSM for colorectal cancer (CRC) that has been used to inform national CRC screening guidelines.

Background: In 2014, the Centers for Medicare and Medicaid Services (CMS) began covering a multitarget stool DNA (mtSDNA) test for colorectal cancer (CRC) screening of Medicare beneficiaries. In this study, we evaluated whether mtSDNA testing is a cost-effective alternative to other CRC screening strategies reimbursed by CMS, and if not, under what conditions it could be., Methods: We use three independently-developed microsimulation models to simulate a cohort of previously unscreened US 65-year-olds who are screened with triennial mtSDNA testing, or one of six other reimbursed screening strategies. Main outcome measures are discounted life-years gained (LYG) and lifetime costs (CMS perspective), threshold reimbursement rates, and threshold adherence rates. Outcomes are expressed as the median and range across models., Results: Compared to no screening, triennial mtSDNA screening resulted in 82 (range: 79-88) LYG per 1,000 simulated individuals. This was more than for five-yearly sigmoidoscopy (80 (range: 71-89) LYG), but fewer than for every other simulated strategy. At its 2017 reimbursement rate of $512, mtSDNA was the most costly strategy, and even if adherence were 30% higher than with other strategies, it would not be a cost-effective alternative. At a substantially reduced reimbursement rate ($6-18), two models found that triennial mtSDNA testing was an efficient and potentially cost-effective screening option., Conclusions: Compared to no screening, triennial mtSDNA screening reduces CRC incidence and mortality at acceptable costs. However, compared to nearly all other CRC screening strategies reimbursed by CMS it is less effective and considerably more costly, making it an inefficient screening option., Competing Interests: This work was supported by contract HHSM-500-2012-00008I with The MITRE Corporation. CMR was affiliated with RAND Corporation, but did not receive any financial support for this work. BS is currently affiliated with CVS Health but was not affiliated at the time of the study. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Despite the importance of characterizing colonoscopy indication for quality monitoring and cancer screening program evaluation, there is no standard approach to documenting colonoscopy indication in medical records., Methods: We applied two algorithms in three health care systems to assign colonoscopy indication to persons 50-89 years old who received a colonoscopy during 2010-2013. Both algorithms used standard procedure, diagnostic, and laboratory codes. One algorithm, the KPNC algorithm, used a hierarchical approach to classify exam indication into: diagnostic, surveillance, or screening; whereas the other, the SEARCH algorithm, used a logistic regression-based algorithm to provide the probability that colonoscopy was performed for screening. Gold standard assessment of indication was from medical records abstraction., Results: There were 1,796 colonoscopy exams included in analyses; age and racial/ethnic distributions of participants differed across health care systems. The KPNC algorithm's sensitivities and specificities for screening indication ranged from 0.78-0.82 and 0.78-0.91, respectively; sensitivities and specificities for diagnostic indication ranged from 0.78-0.89 and 0.74-0.82, respectively. The KPNC algorithm had poor sensitivities (ranging from 0.11-0.67) and high specificities for surveillance exams. The Area Under the Curve (AUC) of the SEARCH algorithm for screening indication ranged from 0.76-0.84 across health care systems. For screening indication, the KPNC algorithm obtained higher specificities than the SEARCH algorithm at the same sensitivity., Conclusion: Despite standardized implementation of these indication algorithms across three health care systems, the capture of colonoscopy indication data was imperfect. Thus, we recommend that standard, systematic documentation of colonoscopy indication should be added to medical records to ensure efficient and accurate data capture., Competing Interests: The authors have no competing interests to declare.

Background: Pragmatic clinical trials often use automated data sources such as electronic health records, claims, or registries to identify eligible individuals and collect outcome information. A specific advantage that this automated data collection often yields is having data on potential participants when design decisions are being made. We outline how this data can be used to inform trial design., Methods: Our work is motivated by a pragmatic clinical trial evaluating the impact of suicide-prevention outreach interventions on fatal and non-fatal suicide attempts in the 18 months after randomization. We illustrate our recommended approaches for designing pragmatic clinical trials using historical data from the health systems participating in this study. Specifically, we illustrate how electronic health record data can be used to inform the selection of trial eligibility requirements, to estimate the distribution of participant characteristics over the course of the trial, and to conduct power and sample size calculations., Results: Data from 122,873 people with patient health questionnaire (PHQ) responses, recorded in their electronic health records between 1 July 2010 and 31 March 2012, were used to show that the suicide attempt rate in the 18 months following completion of the questionnaire varies by response to item nine of the PHQ. We estimated that the proportion of individuals with a prior recorded elevated PHQ (i.e. history of suicidal ideation) would decrease from approximately 50% at the beginning of a trial to about 5%, 50 weeks later. Using electronic health record data, we conducted simulations to estimate the power to detect a 25% reduction in suicide attempts. Simulation-based power calculations estimated that randomizing 8000 participants per randomization arm would allow 90% power to detect a 25% reduction in the suicide attempt rate in the intervention arm compared to usual care at an alpha rate of 0.05., Conclusions: Historical data can be used to inform the design of pragmatic clinical trials, a strength of trials that use automated data collection for randomizing participants and assessing outcomes. In particular, realistic sample size calculations can be conducted using real-world data from the health systems in which the trial will be conducted. Data-informed trial design should yield more realistic estimates of statistical power and maximize efficiency of trial recruitment.

Emerging health care research paradigms such as comparative effectiveness research (CER), patient-centered outcome research (PCOR), and precision medicine (PM) share one ultimate goal: constructing evidence to provide the right treatment to the right patient at the right time. We argue that to succeed at this goal, it is crucial to have both timely access to individual-level data and fine geographic granularity in the data. Existing data will continue to be an important resource for observational studies as new data sources are developed. We examined widely used publicly funded health databases and population-based survey systems and found four ways they could be improved to better support the new research paradigms: (1) finer and more consistent geographic granularity, (2) more complete geographic coverage of the US population, (3) shorter time from data collection to data release, and (4) improved environments for restricted data access. We believe that existing data sources, if utilized optimally, and newly developed data infrastructures will both play a key role in expanding our insight into what treatments, at what time, work for each patient.

Objectives: Chronic low back pain (CLBP) and chronic neck pain (CNP) are the most common types of chronic pain, and chiropractic spinal manipulation is a common nonpharmacologic treatment. This study presents the characteristics of a large United States sample of chiropractic patients with CLBP and CNP., Methods: Data were collected from chiropractic patients using multistage systematic stratified sampling with 4 sampling levels: regions and states, sites (ie, metropolitan areas), providers and clinics, and patients. The sites and regions were San Diego, California; Tampa, Florida; Minneapolis, Minnesota; Seneca Falls and Upstate New York; Portland, Oregon; and Dallas, Texas. Data were collected from patients through an iPad-based prescreening questionnaire in the clinic and emailed links to full screening and baseline online questionnaires. The goal was 20 providers or clinics and 7 patients with CLBP and 7 with CNP from each clinic., Results: We had 6342 patients at 125 clinics complete the prescreening questionnaire, 3333 patients start the full screening questionnaire, and 2024 eligible patients completed the baseline questionnaire: 518 with CLBP only, 347 with CNP only, and 1159 with both. In general, most of this sample were highly-educated, non-Hispanic, white females with at least partial insurance coverage for chiropractic care who have been in pain and using chiropractic care for years. Over 90% reported high satisfaction with their care, few used narcotics, and avoiding surgery was the most important reason they chose chiropractic care., Conclusions: Given the prevalence of CLBP and CNP, the need to find effective nonpharmacologic alternatives for chronic pain, and the satisfaction these patients found with their care, further study of these patients is worthwhile., (Copyright © 2018. Published by Elsevier Inc.)

Background: Patients who receive an abnormal cancer screening result require follow-up for diagnostic testing, but the time to follow-up varies across patients and practices. Methods: We used a simulation study to estimate the change in lifetime screening benefits when time to follow-up for breast, cervical, and colorectal cancers was increased. Estimates were based on four independently developed microsimulation models that each simulated the life course of adults eligible for breast (women ages 50-74 years), cervical (women ages 21-65 years), or colorectal (adults ages 50-75 years) cancer screening. We assumed screening based on biennial mammography for breast cancer, triennial Papanicolaou testing for cervical cancer, and annual fecal immunochemical testing for colorectal cancer. For each cancer type, we simulated diagnostic testing immediately and at 3, 6, and 12 months after an abnormal screening exam. Results: We found declines in screening benefit with longer times to diagnostic testing, particularly for breast cancer screening. Compared to immediate diagnostic testing, testing at 3 months resulted in reduced screening benefit, with fewer undiscounted life years gained per 1,000 screened (breast: 17.3%, cervical: 0.8%, colorectal: 2.0% and 2.7%, from two colorectal cancer models), fewer cancers prevented (cervical: 1.4% fewer, colorectal: 0.5% and 1.7% fewer, respectively), and, for breast and colorectal cancer, a less favorable stage distribution. Conclusions: Longer times to diagnostic testing after an abnormal screening test can decrease screening effectiveness, but the impact varies substantially by cancer type. Impact: Understanding the impact of time to diagnostic testing on screening effectiveness can help inform quality improvement efforts. Cancer Epidemiol Biomarkers Prev; 27(2); 158-64. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Background and Objective: Little is known about the feasibility, effectiveness, and sustainability of CQI approaches in substance use disorder treatment settings., Methods: In the initial phase of this study, eight programs were randomly assigned to receive a CQI intervention or to a waitlist control condition to obtain preliminary information about potential effectiveness. In the second phase, the initially assigned control programs received the CQI intervention to gain additional information about intervention feasibility while sustainability was explored among the initially assigned intervention programs., Results and Conclusions: Although CQI was feasible and sustainable, demonstrating its effectiveness using administrative data was challenging suggesting the need to better align performance measurement systems with CQI efforts. Further, although the majority of staff were enthusiastic about utilizing this approach and reported provider and patient benefits, many noted that dedicated time was needed in order to implement and sustain it., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Exposures derived from electronic health records (EHR) may be misclassified, leading to biased estimates of their association with outcomes of interest. An example of this problem arises in the context of cancer screening where test indication, the purpose for which a test was performed, is often unavailable. This poses a challenge to understanding the effectiveness of screening tests because estimates of screening test effectiveness are biased if some diagnostic tests are misclassified as screening. Prediction models have been developed for a variety of exposure variables that can be derived from EHR, but no previous research has investigated appropriate methods for obtaining unbiased association estimates using these predicted probabilities. The full likelihood incorporating information on both the predicted probability of exposure-class membership and the association between the exposure and outcome of interest can be expressed using a finite mixture model. When the regression model of interest is a generalized linear model (GLM), the expectation-maximization algorithm can be used to estimate the parameters using standard software for GLMs. Using simulation studies, we compared the bias and efficiency of this mixture model approach to alternative approaches including multiple imputation and dichotomization of the predicted probabilities to create a proxy for the missing predictor. The mixture model was the only approach that was unbiased across all scenarios investigated. Finally, we explored the performance of these alternatives in a study of colorectal cancer screening with colonoscopy. These findings have broad applicability in studies using EHR data where gold-standard exposures are unavailable and prediction models have been developed for estimating proxies., Competing Interests: Conflict of Interest: All authors declare that they have no conflicts of interest.

Background: Population outreach strategies are increasingly used to improve colorectal cancer (CRC) screening. The influence of primary care on cancer screening in this context is unknown., Objective: To assess associations between primary care provider (PCP) visits and receipt of CRC screening and colonoscopy after a positive fecal immunochemical (FIT) or fecal occult blood test (FOBT)., Design: Population-based cohort study., Participants: A total of 968,072 patients ages 50-74 years who were not up to date with CRC screening in 2011 in four integrated healthcare systems (three with screening outreach programs using FIT kits) in the Population-Based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium., Measures: Demographic, clinical, PCP visit, and CRC screening data were obtained from electronic health records and administrative databases. We examined associations between PCP visits in 2011 and receipt of FIT/FOBT, screening colonoscopy, or flexible sigmoidoscopy (CRC screening) in 2012 and follow-up colonoscopy within 3 months of a positive FIT/FOBT in 2012. We used multivariable logistic regression and propensity score models to adjust for confounding., Results: Fifty-eight percent of eligible patients completed a CRC screening test in 2012, most by FIT. Those with a greater number of PCP visits had higher rates of CRC screening at all sites. Patients with ≥1 PCP visit had nearly twice the adjusted-odds of CRC screening (OR = 1.88, 95 % CI: 1.86-1.89). Overall, 79.6 % of patients with a positive FIT/FOBT completed colonoscopy within 3 months. Patients with ≥1 PCP visit had 30 % higher adjusted odds of completing colonoscopy after positive FIT/FOBT (OR = 1.30; 95 % CI: 1.22-1.40)., Conclusions: Patients with a greater number of PCP visits had higher rates of both incident CRC screening and colonoscopy after positive FIT/FOBT, even in health systems with active population health outreach programs. In this era of virtual care and population outreach, primary care visits remain an important mechanism for engaging patients in cancer screening., Competing Interests: Compliance with ethical standards Funding This study was conducted as part of the NCI-funded consortium Population-Based Research Optimizing Screening through Personalized Regiments (PROSPR), with support from NIH/NCI-funded PROSPR cooperative agreements (grant numbers U54CA163308, U01CA163304, U54CA163261, U5U54CA163262, U54CA163303, U54CA163307, U54CA163313). Dr. Halm was also supported in part by the AHRQ Center for Patient-Centered Outcomes Research (R24 HS022418). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or AHRQ. Conflict of Interest The authors have no conflicts of interest to report, other than receiving funding from the NCI as investigators in the PROSPR U54 grants listed above.

Introduction: Timely follow-up of abnormal tests is critical to the effectiveness of cancer screening, but may vary by screening test, healthcare system, and sociodemographic group., Methods: Timely follow-up of abnormal mammogram and fecal occult blood testing or fecal immunochemical tests (FOBT/FIT) were compared by race/ethnicity using Population-Based Research Optimizing Screening through Personalized Regimens consortium data. Participants were women with an abnormal mammogram (aged 40-75 years) or FOBT/FIT (aged 50-75 years) in 2010-2012. Analyses were performed in 2015. Timely follow-up was defined as colonoscopy ≤3 months following positive FOBT/FIT; additional imaging or biopsy ≤3 months following Breast Imaging Reporting and Data System Category 0, 4, or 5 mammograms; or ≤9 months following Category 3 mammograms. Logistic regression was used to model receipt of timely follow-up adjusting for study site, age, year, insurance, and income., Results: Among 166,602 mammograms, 10.7% were abnormal; among 566,781 FOBT/FITs, 4.3% were abnormal. Nearly 96% of patients with abnormal mammograms received timely follow-up versus 68% with abnormal FOBT/FIT. There was greater variability in receipt of follow-up across healthcare systems for positive FOBT/FIT than for abnormal mammograms. For mammography, black women were less likely than whites to receive timely follow-up (91.8% vs 96.0%, OR=0.71, 95% CI=0.51, 0.97). For FOBT/FIT, Hispanics were more likely than whites to receive timely follow-up than whites (70.0% vs 67.6%, OR=1.12, 95% CI=1.04, 1.21)., Conclusions: Timely follow-up among women was more likely for abnormal mammograms than FOBT/FITs, with small variations in follow-up rates by race/ethnicity and larger variation across healthcare systems., (Copyright © 2016 American Journal of Preventive Medicine. All rights reserved.)

Introduction: Expert recommendations differ for colorectal cancer screening in the elderly. Recent studies suggest that healthy adults aged >75 years may benefit from screening. This study examined screening use and follow-up, and how they varied by health status within age strata, among a large cohort of elderly individuals in community settings., Methods: A population-based, longitudinal cohort study was conducted among health plan members aged 65-89 years enrolled during 2011-2012 in three integrated healthcare systems participating in the Population-Based Research Optimizing Screening through Personalized Regimens consortium. Comorbidity measurements used the Charlson index. Analyses, conducted in 2015, comprised descriptive statistics and multivariable modeling that estimated age by comorbidity-specific percentages of patients for two outcomes: colorectal cancer screening uptake and follow-up of abnormal fecal blood tests., Results: Among 846,267 patients, 72% were up-to-date with colorectal cancer screening. Of patients with a positive fecal blood test, 65% received follow-up colonoscopy within 3 months. Likelihood of being up-to-date and receiving timely follow-up was significantly lower for patients aged ≥76 years than their younger counterparts (p<0.001). Comorbidity was less influential than age and more strongly related to timely follow-up than being up-to-date. In all age groups, considerable numbers of patients with no/low comorbidity were not up-to-date or did not receive timely follow-up., Conclusions: In three integrated healthcare systems, many older, relatively healthy patients were not screening up-to-date, and some relatively young, healthy patients did not receive timely follow-up. Findings suggest a need for re-evaluating age-based screening guidelines and improving screening completion among the elderly., (Published by Elsevier Inc.)

Electronic health records and administrative databases provide rich, longitudinal data for health-related research. These data cover large, diverse populations creating excellent research opportunities, but have limitations. In particular, information is available only for individuals who are enrolled in a particular health system; thus, studies often exclude individual's with short enrollment history. Such cohort restriction may cause selection bias in absolute risk estimates for the full enrollee population. We use hazard ratios (HRs) to estimate the association between length of prior enrollment and cancer and all-cause mortality risk. HRs different from one indicate restricted cohorts would produce biased risk estimates for the full enrollee population. Our study sample included 170,708 enrollees of a Western Washington healthcare delivery system. Unadjusted models found individuals with 10 or more years of prior enrollment had higher risk of cancer and death compared to those with less than 5 years prior enrollment (HRs ranged from 1.29 - 3.01). Age- and sex-adjusted models accounted for much of this difference (HRs: 0.93 - 1.24). Models adjusting for additional covariates had similar results (HRs: 0.91 - 1.14). After evaluating potential selection bias, we conclude that, in this setting, age- and sex-standardizing risk estimates can remove most of the bias due to lengthy, prior-enrollment cohort restrictions. Before generalizing estimates based on a selected sample of patients meeting prior enrollment criteria, researchers should assess the potential for selection bias.

Background: Microsimulation models synthesize evidence about disease processes and interventions, providing a method for predicting long-term benefits and harms of prevention, screening, and treatment strategies. Because models often require assumptions about unobservable processes, assessing a model's predictive accuracy is important., Methods: We validated 3 colorectal cancer (CRC) microsimulation models against outcomes from the United Kingdom Flexible Sigmoidoscopy Screening (UKFSS) Trial, a randomized controlled trial that examined the effectiveness of one-time flexible sigmoidoscopy screening to reduce CRC mortality. The models incorporate different assumptions about the time from adenoma initiation to development of preclinical and symptomatic CRC. Analyses compare model predictions to study estimates across a range of outcomes to provide insight into the accuracy of model assumptions., Results: All 3 models accurately predicted the relative reduction in CRC mortality 10 years after screening (predicted hazard ratios, with 95% percentile intervals: 0.56 [0.44, 0.71], 0.63 [0.51, 0.75], 0.68 [0.53, 0.83]; estimated with 95% confidence interval: 0.56 [0.45, 0.69]). Two models with longer average preclinical duration accurately predicted the relative reduction in 10-year CRC incidence. Two models with longer mean sojourn time accurately predicted the number of screen-detected cancers. All 3 models predicted too many proximal adenomas among patients referred to colonoscopy., Conclusion: Model accuracy can only be established through external validation. Analyses such as these are therefore essential for any decision model. Results supported the assumptions that the average time from adenoma initiation to development of preclinical cancer is long (up to 25 years), and mean sojourn time is close to 4 years, suggesting the window for early detection and intervention by screening is relatively long. Variation in dwell time remains uncertain and could have important clinical and policy implications., (© The Author(s) 2016.)