Amy Knudsen’s Publications

@article{pmid38552671,

title = {Effectiveness and Cost-Effectiveness of Colorectal Cancer Screening With a Blood Test That Meets the Centers for Medicare \& Medicaid Services Coverage Decision},

author = {Rosita van den Puttelaar and Pedro Nascimento de Lima and Amy B Knudsen and Carolyn M Rutter and Karen M Kuntz and Lucie de Jonge and Fernando Alarid Escudero and David Lieberman and Ann G Zauber and Anne I Hahn and John M Inadomi and Iris Lansdorp-Vogelaar},

doi = {10.1053/j.gastro.2024.02.012},

issn = {1528-0012},

year  = {2024},

date = {2024-03-01},

journal = {Gastroenterology},

abstract = {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.nnMETHODS: 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.nnRESULTS: 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.nnCONCLUSION: 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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38086003,

title = {Cost-Effectiveness Analysis of Screening for Pancreatic Cancer Among High-Risk Populations},

author = {Mary Linton B Peters and Andrew Eckel and Claudia L Seguin and Barak Davidi and David H Howard and Amy B Knudsen and Pari V Pandharipande},

doi = {10.1200/OP.23.00495},

issn = {2688-1535},

year  = {2024},

date = {2024-02-01},

urldate = {2024-02-01},

journal = {JCO Oncol Pract},

volume = {20},

issue = {2},

pages = {278-290},

abstract = {PURPOSE: We evaluated the potential cost-effectiveness of combined magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS) screening for pancreatic ductal adenocarcinoma (PDAC) among populations at high risk for the disease.nnMETHODS: We used a microsimulation model of the natural history of PDAC to estimate the lifetime health benefits, costs, and cost-effectiveness of PDAC screening among populations with specific genetic risk factors for PDAC, including  and , , , Lynch syndrome, , , and . For each high-risk population, we simulated 29 screening strategies, defined by starting age and frequency. Screening included MRI with follow-up EUS in a subset of patients. Costs of tests were based on Medicare reimbursement for MRI, EUS, fine-needle aspiration biopsy, and pancreatectomy. Cancer-related cost by stage of disease and phase of treatment was based on the literature. For each high-risk population, we performed an incremental cost-effectiveness analysis, assuming a willingness-to-pay (WTP) threshold of $100,000 US dollars (USD) per quality-adjusted life year (QALY) gained.nnRESULTS: For men with relative risk (RR) 12.33 () and RR 28 (), annual screening was cost-effective, starting at age 55 and 40 years, respectively. For women, screening was only cost-effective for those with RR 28 (), with annual screening starting at age 45 years.nnCONCLUSION: Combined MRI/EUS screening may be a cost-effective approach for the highest-risk populations (among mutations considered, those with RR \>12). However, for those with moderate risk (RR, 5-12), screening would only be cost-effective at higher WTP thresholds (eg, $200K USD/QALY) or with once-only screening.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37991759,

title = {Estimated US Cancer Deaths Prevented With Increased Use of Lung, Colorectal, Breast, and Cervical Cancer Screening},

author = {Amy B Knudsen and Amy Trentham-Dietz and Jane J Kim and Jeanne S Mandelblatt and Rafael Meza and Ann G Zauber and Philip E Castle and Eric J Feuer},

doi = {10.1001/jamanetworkopen.2023.44698},

issn = {2574-3805},

year  = {2023},

date = {2023-11-01},

journal = {JAMA Netw Open},

volume = {6},

number = {11},

pages = {e2344698},

abstract = {IMPORTANCE: Increased use of recommended screening could help achieve the Cancer Moonshot goal of reducing US cancer deaths.nnOBJECTIVE: To estimate the number of cancer deaths that could be prevented with a 10-percentage point increase in the use of US Preventive Services Task Force (USPSTF)-recommended screening.nnDESIGN, SETTING, AND PARTICIPANTS: This decision analytical model study is an extension of previous studies conducted for the USPSTF from 2018 to 2023. This study simulated contemporary cohorts of US adults eligible for lung, colorectal, breast, and cervical cancer screening.nnEXPOSURES: Annual low-dose computed lung tomography among eligible adults aged 50 to 80 years; colonoscopy every 10 years among adults aged 45 to 75 years; biennial mammography among female adults aged 40 to 74 years; and triennial cervical cytology screening among female adults aged 21 to 29 years, followed by human papillomavirus testing every 5 years from ages 30 to 65 years.nnMAIN OUTCOMES AND MEASURES: Estimated number of cancer deaths prevented with a 10-percentage point increase in screening use, assuming screening commences at the USPSTF-recommended starting age and continues throughout the lifetime. Outcomes were presented 2 ways: (1) per 100 000 and (2) among US adults in 2021; and they were expressed among the target population at the age of screening initiation. For lung cancer, estimates were among those who will also meet the smoking eligibility criteria during their lifetime. Harms from increased uptake were also reported.nnRESULTS: A 10-percentage point increase in screening use at the age that USPSTF recommended screening commences was estimated to prevent 226 lung cancer deaths (range across models within the cancer site, 133-332 deaths), 283 (range, 263-313) colorectal cancer deaths, 82 (range, 61-106) breast cancer deaths, and 81 (1 model; no range available) cervical cancer deaths over the lifetimes of 100 000 persons eligible for screening. These rates corresponded with an estimated 1010 (range, 590-1480) lung cancer deaths prevented, 11 070 (range, 10 280-12 250) colorectal cancer deaths prevented, 1790 (range, 1330-2310) breast cancer deaths prevented, and 1710 (no range available) cervical cancer deaths prevented over the lifetimes of eligible US residents at the recommended age to initiate screening in 2021. Increased uptake was also estimated to generate harms, including 100 000 (range, 45 000-159 000) false-positive lung scans, 6000 (range, 6000-7000) colonoscopy complications, 300 000 (range, 295 000-302 000) false-positive mammograms, and 348 000 (no range available) colposcopies over the lifetime.nnCONCLUSIONS AND RELEVANCE: In this decision analytical model study, a 10-percentage point increase in uptake of USPSTF-recommended lung, colorectal, breast, and cervical cancer screening at the recommended starting age was estimated to yield important reductions in cancer deaths. Achieving these reductions is predicated on ensuring equitable access to screening.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37454978b,

title = {NordICC Trial Results in Line With Expected Colorectal Cancer Mortality Reduction After Colonoscopy: A Modeling Study},

author = {Danica M N van den Berg and Pedro Nascimento de Lima and Amy B Knudsen and Carolyn M Rutter and David Weinberg and Iris Lansdorp-Vogelaar and },

doi = {10.1053/j.gastro.2023.06.035},

issn = {1528-0012},

year  = {2023},

date = {2023-10-01},

journal = {Gastroenterology},

volume = {165},

number = {4},

pages = {1077--1079.e2},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37406750c,

title = {Ultrasound Surveillance of Small, Incidentally Detected Gallbladder Polyps: Projected Benefits by Sex, Age, and Comorbidity Level},

author = {Claudia L Seguin and Barak Davidi and Mary Linton B Peters and Andrew Eckel and Mukesh G Harisinghani and Reece J Goiffon and Amy B Knudsen and Pari V Pandharipande},

doi = {10.1016/j.jacr.2023.05.015},

issn = {1558-349X},

year  = {2023},

date = {2023-10-01},

urldate = {2023-10-01},

journal = {J Am Coll Radiol},

volume = {20},

number = {10},

pages = {1031-1041},

abstract = {OBJECTIVE: Incidentally detected gallbladder polyps are commonly encountered when performing upper abdominal ultrasound. Our purpose was to estimate the life expectancy (LE) benefit of ultrasound-based gallbladder surveillance in patients with small (6-7 to \<10 mm), incidentally detected gallbladder polyps, accounting for patient sex, age, and comorbidity level.nnMETHODS: We developed a decision-analytic Markov model to evaluate hypothetical cohorts of women and men with small gallbladder polyps, with varying age (66-80 years) and comorbidity level (none, mild, moderate, severe). Drawing from current evidence, in the base case, we assumed no increased risk of gallbladder cancer in patients with small gallbladder polyps. To estimate maximal possible LE gains from surveillance, we assumed perfect cancer control consequent to 5 years of surveillance. We varied key assumptions including cancer risk and test performance characteristics in sensitivity analysis.nnRESULTS: Projected LE gains from surveillance were \<3 days across most cohorts and scenarios evaluated. For 66- and 80-year-olds with no comorbidities, LE gains were 1.46 and 1.45 days, respectively, for women, and 0.67 and 0.75 days for men. With 10 years of surveillance, LE gains increased to 2.94 days for 66-year-old women with no comorbidities (men: 1.35 days). If we assumed a 10% increase in gallbladder cancer risk among individuals with polyps, LE gains increased slightly to 1.60 days for 66-year-old women with no comorbidities (men: 0.74 days). Results were sensitive to test performance and surgical mortality.nnDISCUSSION: Even under unrealistic, optimistic assumptions of cancer control, ultrasound surveillance of incidentally detected small gallbladder polyps provided limited benefit.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37454978,

title = {NordICC trial results in line with expected colorectal cancer mortality reduction after colonoscopy: a modelling study},

author = {Danica M N van den Berg and Pedro Nascimento de Lima and Amy B Knudsen and Carolyn M Rutter and David Weinberg and Iris Lansdorp-Vogelaar and },

doi = {10.1053/j.gastro.2023.06.035},

issn = {1528-0012},

year  = {2023},

date = {2023-07-01},

journal = {Gastroenterology},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36948424,

title = {Randomized Trial of Facilitated Adherence to Screening Colonoscopy vs Sequential Fecal-Based Blood Test},

author = {Ann G Zauber and Sidney J Winawer and Michael J O'Brien and Glenn M Mills and John I Allen and Andrew D Feld and Paul A Jordan and Martin Fleisher and Irene Orlow and Reinier G S Meester and Iris Lansdorp-Vogelaar and Carolyn M Rutter and Amy B Knudsen and Margaret Mandelson and Aasma Shaukat and Robin B Mendelsohn and Anne I Hahn and Stephanie M Lobaugh and Brittany Soto Palmer and Victoria Serrano and Julie R Kumar and Sara E Fischer and Jennifer C Chen and Sharon Bayuga-Miller and Deborah Kuk and Kelli O'Connell and Timothy R Church},

doi = {10.1053/j.gastro.2023.03.206},

issn = {1528-0012},

year  = {2023},

date = {2023-07-01},

urldate = {2023-03-01},

journal = {Gastroenterology},

volume = {165},

issue = {1},

pages = {252-266},

abstract = {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.nnMETHODS: 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.nnRESULTS: 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.nnCONCLUSIONS: 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.nnCLINICALTRIALS: gov, Number: NCT00102011.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37406750,

title = {Ultrasound Surveillance of Small Incidentally Detected Gallbladder Polyps: Projected Benefits by Sex, Age, and Comorbidity Level},

author = {Claudia L Seguin and Barak Davidi and Mary Linton B Peters and Andrew Eckel and Mukesh G Harisinghani and Reece J Goiffon and Amy B Knudsen and Pari V Pandharipande},

doi = {10.1016/j.jacr.2023.05.015},

issn = {1558-349X},

year  = {2023},

date = {2023-07-01},

urldate = {2023-07-01},

journal = {J Am Coll Radiol},

volume = {S1546-1440},

issue = {23},

pages = {00475-1},

abstract = {OBJECTIVE: Incidentally detected gallbladder polyps are commonly encountered when performing upper abdominal ultrasound. Our purpose was to estimate the life expectancy (LE) benefit of ultrasound-based gallbladder surveillance in patients with small (6-7 to \<10 mm), incidentally detected gallbladder polyps, accounting for patient sex, age, and comorbidity level.nnMETHODS: We developed a decision-analytic Markov model to evaluate hypothetical cohorts of women and men with small gallbladder polyps, with varying age (66-80 years) and comorbidity level (none, mild, moderate, severe). Drawing from current evidence, in the base case, we assumed no increased risk of gallbladder cancer in patients with small gallbladder polyps. To estimate maximal possible LE gains from surveillance, we assumed perfect cancer control consequent to five years of surveillance. We varied key assumptions including cancer risk and test performance characteristics in sensitivity analysis.nnRESULTS: Projected LE gains from surveillance were \< 3 days across most cohorts and scenarios evaluated. For 66- and 80-year-olds with no comorbidities, LE gains were 1.46 and 1.45 days, respectively, for women, and 0.67 and 0.75 days for men. With ten years of surveillance, LE gains increased to 2.94 days for 66-year-old women with no comorbidities (men: 1.35 days). If we assumed a 10% increase in gallbladder cancer risk among individuals with polyps, LE gains increased slightly to 1.60 days for 66-year-old women with no comorbidities (men: 0.74 days). Results were sensitive to test performance and surgical mortality.nnDISCUSSION: Even under unrealistic, optimistic assumptions of cancer control, ultrasound surveillance of incidentally detected small gallbladder polyps provided limited benefit.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37294571,

title = {Estimated Reductions in Opioid Overdose Deaths With Sustainment of Public Health Interventions in 4 US States},

author = {Jagpreet Chhatwal and Peter P Mueller and Qiushi Chen and Neeti Kulkarni and Madeline Adee and Gary Zarkin and Marc R LaRochelle and Amy B Knudsen and Carolina Barbosa},

doi = {10.1001/jamanetworkopen.2023.14925},

issn = {2574-3805},

year  = {2023},

date = {2023-06-01},

journal = {JAMA Netw Open},

volume = {6},

number = {6},

pages = {e2314925},

abstract = {IMPORTANCE: In 2021, more than 80 000 US residents died from an opioid overdose. Public health intervention initiatives, such as the Helping to End Addiction Long-term (HEALing) Communities Study (HCS), are being launched with the goal of reducing opioid-related overdose deaths (OODs).nnOBJECTIVE: To estimate the change in the projected number of OODs under different scenarios of the duration of sustainment of interventions, compared with the status quo.nnDESIGN, SETTING, AND PARTICIPANTS: This decision analytical model simulated the opioid epidemic in the 4 states participating in the HCS (ie, Kentucky, Massachusetts, New York, and Ohio) from 2020 to 2026. Participants were a simulated population transitioning from opioid misuse to opioid use disorder (OUD), overdose, treatment, and relapse. The model was calibrated using 2015 to 2020 data from the National Survey on Drug Use and Health, the US Centers for Disease Control and Prevention, and other sources for each state. The model accounts for reduced initiation of medications for OUD (MOUDs) and increased OODs during the COVID-19 pandemic.nnEXPOSURE: Increasing MOUD initiation by 2- or 5-fold, improving MOUD retention to the rates achieved in clinical trial settings, increasing naloxone distribution efforts, and furthering safe opioid prescribing. An initial 2-year duration of interventions was simulated, with potential sustainment for up to 3 additional years.nnMAIN OUTCOMES AND MEASURES: Projected reduction in number of OODs under different combinations and durations of sustainment of interventions.nnRESULTS: Compared with the status quo, the estimated annual reduction in OODs at the end of the second year of interventions was 13% to 17% in Kentucky, 17% to 27% in Massachusetts, 15% to 22% in New York, and 15% to 22% in Ohio. Sustaining all interventions for an additional 3 years was estimated to reduce the annual number of OODs at the end of the fifth year by 18% to 27% in Kentucky, 28% to 46% in Massachusetts, 22% to 34% in New York, and 25% to 41% in Ohio. The longer the interventions were sustained, the better the outcomes; however, these positive gains would be washed out if interventions were not sustained.nnCONCLUSIONS AND RELEVANCE: In this decision analytical model study of the opioid epidemic in 4 US states, sustained implementation of interventions, including increased delivery of MOUDs and naloxone supply, was found to be needed to reduce OODs and prevent deaths from increasing again.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35615677,

title = {Characterization and Valuation of the Uncertainty of Calibrated Parameters in Microsimulation Decision Models},

author = {Fernando Alarid-Escudero and Amy B Knudsen and Jonathan Ozik and Nicholson Collier and Karen M Kuntz},

doi = {10.3389/fphys.2022.780917},

issn = {1664-042X},

year  = {2022},

date = {2022-01-01},

journal = {Front Physiol},

volume = {13},

pages = {780917},

abstract = { We evaluated the implications of different approaches to characterize the uncertainty of calibrated parameters of microsimulation decision models (DMs) and quantified the value of such uncertainty in decision making.  We calibrated the natural history model of CRC to simulated epidemiological data with different degrees of uncertainty and obtained the joint posterior distribution of the parameters using a Bayesian approach. We conducted a probabilistic sensitivity analysis (PSA) on all the model parameters with different characterizations of the uncertainty of the calibrated parameters. We estimated the value of uncertainty of the various characterizations with a value of information analysis. We conducted all analyses using high-performance computing resources running the Extreme-scale Model Exploration with Swift (EMEWS) framework.  The posterior distribution had a high correlation among some parameters. The parameters of the Weibull hazard function for the age of onset of adenomas had the highest posterior correlation of -0.958. When comparing full posterior distributions and the maximum-a-posteriori estimate of the calibrated parameters, there is little difference in the spread of the distribution of the CEA outcomes with a similar expected value of perfect information (EVPI) of $653 and $685, respectively, at a willingness-to-pay (WTP) threshold of $66,000 per quality-adjusted life year (QALY). Ignoring correlation on the calibrated parameters' posterior distribution produced the broadest distribution of CEA outcomes and the highest EVPI of $809 at the same WTP threshold.  Different characterizations of the uncertainty of calibrated parameters affect the expected value of eliminating parametric uncertainty on the CEA. Ignoring inherent correlation among calibrated parameters on a PSA overestimates the value of uncertainty.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Knudsen2021a,

title = {Colorectal Cancer Screening in Young Adults.},

author = {Amy Knudsen and Carolyn M Rutter and Reinier G S Meester and Iris Lansdorp-Vogelaar and Ann G Zauber and Karen M Kuntz},

url = {https://pubmed.ncbi.nlm.nih.gov/34280341/},

doi = {10.7326/L21-0245},

issn = {1539-3704},

year  = {2021},

date = {2021-07-01},

journal = {Annals of internal medicine},

volume = {174},

number = {7},

pages = {1039--1040},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{knudsen2021,

title = {Colorectal Cancer Screening: An Updated Modeling Study for the US Preventive Services Task Force},

author = {Amy Knudsen and Carolyn M. Rutter and Elisabeth F. P. Peterse and Anna Lietz and Claudia Seguin and Reinier G. S. Meester and Leslie A. Perdue and Jennifer S. Lin and Rebecca L. Siegel and V. Paul Doria-Rose and Eric J. Feuer and Ann G. Zauber and Karen M. Kuntz and Iris Lansdorp-Vogelaar},

url = {https://doi.org/10.1001/jama.2021.5746},

doi = {10.1001/jama.2021.5746},

issn = {0098-7484},

year  = {2021},

date = {2021-05-01},

journal = {JAMA},

volume = {325},

number = {19},

pages = {1998-2011},

abstract = {The US Preventive Services Task Force (USPSTF) is updating its 2016 colorectal cancer screening recommendations.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.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.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.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.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.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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Peterse2020,

title = {Comparing the cost-effectiveness of innovative colorectal cancer screening tests.},

author = {Elisabeth F. P. Peterse and Reinier G. S. Meester and Lucie Jonge and Amir-Houshang Omidvari and Fernando Alarid-Escudero and Amy Knudsen and Ann G. Zauber and Iris Lansdorp-Vogelaar},

url = {https://pubmed.ncbi.nlm.nih.gov/32761199/},

doi = {10.1093/jnci/djaa103},

issn = {1460-2105},

year  = {2021},

date = {2021-02-01},

journal = {Journal of the National Cancer Institute},

volume = {113},

number = {2},

pages = {154-161},

abstract = {Colorectal cancer (CRC) screening with colonoscopy and the fecal immunochemical test (FIT) is underutilized. Innovative tests could increase screening acceptance. This study determined which of the available alternatives is most promising from a cost-effectiveness perspective. The previously-validated MISCAN-Colon model was used to evaluate the cost-effectiveness of screening with capsule endoscopy every 5 or 10 years, computed tomographic colonography (CTC) every 5 years, the multi-target stool DNA (mtSDNA) test every 1 or 3 years, and the methylated SEPT9 DNA plasma assay (mSEPT9) every 1 or 2 years. We also compared these strategies to annual FIT screening and colonoscopy screening every 10 years. Quality-adjusted life-years gained (QALYG), number of colonoscopies, and incremental cost-effectiveness ratios (ICERs) were projected. We assumed a willingness-to-pay threshold of $100,000 per QALYG. Among the alternative tests, CTC every 5 years, annual mSEPT9 and annual mtSDNA screening had ICERs of $1,092, $63,253 and $214,974 per QALYG, respectively. Other screening strategies were more costly and less effective than (a combination of) these three. Under the assumption of perfect adherence, annual mSEPT9 screening resulted in more QALYG, CRC cases averted and CRC deaths averted than annual FIT screening, but led to a high rate of colonoscopy referral (51% after 3 years, 69% after 5 years). The alternative tests were not cost-effective compared to FIT and colonoscopy. This study suggests that for individuals not willing to participate in FIT or colonoscopy screening, mSEPT9 is the test of choice if the high colonoscopy referral rate is acceptable to them.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Rutter2020,

title = {Black and White Differences in Colorectal Cancer Screening and Screening Outcomes: A Narrative Review.},

author = {Carolyn M. Rutter and Amy Knudsen and Jennifer S. Lin and Kathryn E. Bouskill},

url = {https://pubmed.ncbi.nlm.nih.gov/33144285/},

doi = {10.1158/1055-9965.EPI-19-1537},

issn = {1538-7755},

year  = {2021},

date = {2021-01-01},

journal = {Cancer epidemiology, biomarkers \& prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},

volume = {30},

number = {1},

pages = {3-12},

abstract = {Racial disparities in colorectal cancer (CRC) 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 CRC. We reviewed the literature for evidence of these two mechanisms. We show that higher CRC 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 CRC 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 CRC incidence among black patients are primarily driven by lower rates of CRC screening. Our findings highlight the need to increase black patients' access to quality screening to reduce CRC incidence and mortality.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Seguin2020,

title = {Surveillance in Older Women With Incidental Ovarian Cysts: Maximal Projected Benefits by Age and Comorbidity Level.},

author = {Claudia Seguin and Anna Lietz and Jason D. Wright and Alexi Wright and Amy Knudsen and Pari Pandharipande},

url = {https://pubmed.ncbi.nlm.nih.gov/33096089/},

doi = {10.1016/j.jacr.2020.09.048},

issn = {1558-349X},

year  = {2021},

date = {2021-01-01},

journal = {Journal of the American College of Radiology : JACR},

volume = {18},

number = {1 PT A},

pages = {10-18},

abstract = {The aim of this study was to estimate effects on life expectancy (LE) of imaging-based ovarian surveillance after detection of incidental postmenopausal ovarian cysts, under different assumptions of patient age, comorbidity level, and cancer risk and detection. A decision-analytic Markov model was developed to estimate LE benefits. Hypothetical cohorts of postmenopausal women with simple ovarian cysts were evaluated, with varied age (66-80 years) and comorbidity level (none, mild, moderate, severe). For each cohort, imaging "follow-up" (2 years) and "no-follow-up" strategies were compared. Consistent with current evidence, increased cancer risk in patients with cysts was not assumed; however, incident ovarian cancers could be detected during follow-up. To estimate theoretical maximal LE gains from follow-up, perfect ovarian cancer detection and treatment during follow-up were assumed. This and other key assumptions were varied in sensitivity analysis. Projected LE gains from follow-up were limited. For 66-, 70-, 75-, and 80-year-old women with no comorbidities, LE gains were 5.1, 5.1, 4.5, and 3.7 days; with severe comorbidities, they were 3.5, 3.2, 2.7, and 2.1 days. With sensitivity of 50% for cancer detection, they were 3.7 days for 66-year-old women with no comorbidities and 1.3 days for 80-year-old women with severe comorbidities. When cancer risk for women with cysts was assumed to be elevated (1.1 times average risk), LE gains increased only modestly (5.6 and 2.3 days for analogous cohorts). Even in the circumstance of perfect ovarian cancer detection and treatment, surveillance of postmenopausal women (≥66 years of age) with simple cysts affords limited benefits, particularly in women with advanced age and comorbidities.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{DeYoreo2020,

title = {Validation of Colorectal Cancer Models on Long-Term Outcomes from a Randomized Controlled Trial.},

author = {Maria DeYoreo and Iris Lansdorp-Vogelaar and Amy Knudsen and Karen M. Kuntz and Ann G. Zauber and Carolyn M. Rutter},

url = {https://pubmed.ncbi.nlm.nih.gov/33078673/},

doi = {10.1177/0272989X20961095},

issn = {1552-681X},

year  = {2020},

date = {2020-11-01},

journal = {Medical decision making : an international journal of the Society for Medical Decision Making},

volume = {40},

number = {8},

pages = {1034-1040},

abstract = {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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Abuelo2020,

title = {Colorectal Cancer Screening Patient Navigation for Patients with Mental Illness and/or Substance Use Disorder: Pilot Randomized Control Trial.},

author = {Carolina Abuelo and Jeffrey M. Ashburner and Steven J. Atlas and Amy Knudsen and James Morrill and Patricia Corona and Derri Shtasel and Sanja Percac-Lima},

url = {https://pubmed.ncbi.nlm.nih.gov/32762637/},

doi = {10.1080/15504263.2020.1802542},

issn = {1550-4271},

year  = {2020},

date = {2020-08-01},

journal = {Journal of dual diagnosis},

volume = {16},

number = {4},

pages = {438-446},

abstract = {Colorectal cancer (CRC) is the second leading cause of cancer death in the US. Screening has decreased CRC mortality. However, disadvantaged patients, particularly those with mental illness or substance use disorder (SUD), are less likely to be screened. The aim of this trial was to evaluate the impact of a patient navigation program on CRC screening in patients with mental illness and/or SUD. A pilot randomized nonblinded controlled trial was conducted from January to June 2017 in an urban community health center serving a low-income population. We randomized 251 patients aged 50-74 years with mental illness and/or SUD diagnosis overdue for CRC screening to intervention ( = 126) or usual care ( = 125) stratified by mental illness, SUD, or dual diagnosis. Intervention group patients received a letter followed by a phone call from patient navigators. Navigators helped patients overcome their individual barriers to CRC screening including: education, scheduling, explanation of bowel preparation, lack of transportation or accompaniment to appointments. If patient refused colonoscopy, navigators offered fecal occult blood testing. The main measure was proportion of patients completing CRC screening in intervention and usual care groups. Navigators contacted 85 patients (67%) in the intervention group and 26 declined to participate. In intention-to treat analysis, more patients in the intervention group received CRC screening than in the usual care group, 19% versus 10.4% ( = .04). Among 56 intervention patients who received navigation, 19 completed screening (33.9% versus 10.4% in the control group, = .001). In the subgroup of patients with SUD, 20% in the intervention group were screened compared to none in the usual care group ( = .05). A patient navigation program improved CRC screening rates in patients with mental illness and/or SUD. Larger studies in diverse care settings are needed to demonstrate generalizability and explore which modality of CRC screening is most acceptable and which navigator activities are most effective for this vulnerable population. 2016P001322.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Meester2020a,

title = {Intensity of Surveillance for Patients With Colorectal Adenomas.},

author = {Reinier G. S. Meester and Iris Lansdorp-Vogelaar and Sidney J. Winawer and Ann G. Zauber and Amy Knudsen and Uri Ladabaum},

url = {https://pubmed.ncbi.nlm.nih.gov/32176909/},

doi = {10.7326/L19-0829},

issn = {1539-3704},

year  = {2020},

date = {2020-03-01},

urldate = {2020-03-01},

journal = {Annals of internal medicine},

volume = {172},

pages = {442},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Meester2020,

title = {Intensity of Surveillance for Patients With Colorectal Adenomas.},

author = {Reinier G. S. Meester and Iris Lansdorp-Vogelaar and Sidney J. Winawer and Ann G. Zauber and Amy Knudsen and Uri Ladabaum},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32176909},

doi = {10.7326/L19-0829},

issn = {1539-3704},

year  = {2020},

date = {2020-03-01},

urldate = {2020-03-01},

journal = {Annals of internal medicine},

volume = {172},

pages = {442},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Meester2019,

title = {High-Intensity Versus Low-Intensity Surveillance for Patients With Colorectal Adenomas: A Cost-Effectiveness Analysis.},

author = {Reinier G S Meester and Iris Lansdorp-Vogelaar and Sidney J Winawer and Ann G Zauber and Amy Knudsen and Uri Ladabaum},

url = {https://www.ncbi.nlm.nih.gov/pubmed/31546257},

doi = {10.7326/M18-3633},

issn = {1539-3704},

year  = {2019},

date = {2019-11-01},

journal = {Annals of internal medicine},

volume = {171},

number = {9},

pages = {612-622},

abstract = {Surveillance of patients with colorectal adenomas has limited long-term evidence to support current practice. To compare the lifetime benefits and costs of high- versus low-intensity surveillance. Microsimulation model. U.S. cancer registry, cost data, and published literature. U.S. patients aged 50, 60, or 70 years with low-risk adenomas (LRAs) (1 to 2 small adenomas) or high-risk adenomas (HRAs) (3 to 10 small adenomas or ≥1 large adenoma) removed after screening with colonoscopy or fecal immunochemical testing (FIT). Lifetime. Societal. No further screening or surveillance, routine screening after 10 years, low-intensity surveillance (10 years after LRA removal and 5 years after HRA removal), and high-intensity surveillance (5 years after LRA removal and 3 years after HRA removal). Colorectal cancer (CRC) incidence and incremental cost-effectiveness. Without surveillance or screening, lifetime CRC incidence for patients aged 50 years was 10.9% after LRA removal and 17.2% after HRA removal at screening colonoscopy. Subsequent colonoscopic screening, low-intensity surveillance, or high-intensity surveillance decreased incidence by 39%, 46% to 48%, and 55% to 56%, respectively. Incidence of CRC and surveillance benefits were higher for adenomas detected at FIT screening and lower for older patients. High-intensity surveillance cost less than $30 000 per quality-adjusted life-year (QALY) gained compared with low-intensity surveillance. High-intensity surveillance cost less than $100 000 per QALY gained in most alternative scenarios for adenoma recurrence, CRC incidence, longevity, quality of life, screening ages, surveillance ages, test performance, disutilities, and cost. Few surveillance outcome data exist. The model suggests that high-intensity surveillance as recommended in the United States provides modest but clinically relevant benefits over low-intensity surveillance at acceptable cost. National Cancer Institute.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Weaver2019,

title = {Testing for Verification Bias in Reported Malignancy Risks for Side-Branch Intraductal Papillary Mucinous Neoplasms: A Simulation Modeling Approach.},

author = {Davis Weaver and Anna Lietz and Sarah Fletcher Mercaldo and Mary Linton B. Peters and Chin Hur and Chung Yin Kong and Brian M Wolpin and Alec J Megibow and Lincoln L Berland and Amy Knudsen and Pari Pandharipande},

url = {https://www.ncbi.nlm.nih.gov/pubmed/30620679},

doi = {10.2214/AJR.18.20180},

issn = {1546-3141},

year  = {2019},

date = {2019-03-01},

urldate = {2019-03-01},

journal = {AJR. American journal of roentgenology},

volume = {212},

number = {3},

pages = {596-601},

abstract = {The objective of our study was to test for the possibility that published malignancy risks for side-branch intraductal papillary mucinous neoplasms (IPMNs) are overestimates, likely due to verification bias. We tested for possible verification bias using simulation modeling techniques. First, in age-defined hypothetical cohorts of 10 million persons, we projected the frequency of pancreatic ductal adenocarcinoma (PDAC) arising from side-branch IPMNs over 5 years using published estimates of their prevalence (4.4%) and rate of malignant transformation (1.9%). Second, we projected the total number of PDAC cases in corresponding cohorts over the same time horizon using national cancer registry data. For each cohort, we determined whether the percentage of all PDAC cases that arose from side-branch IPMNs (i.e., side-branch IPMN-associated PDAC cases) was clinically plausible using an upper limit of 10% to define plausibility, as estimated from the literature. Model assumptions and parameter uncertainty were evaluated in sensitivity analysis. Across all cohorts, percentages of side-branch IPMN-associated PDACs greatly exceeded 10%. In the base case (mean age = 55.7 years), 80% of PDAC cases arose from side-branch IPMNs (7877/9786). In the oldest cohort evaluated (mean age = 75 years), this estimate was 76% (14,227/18,714). In a secondary analysis, we found that if an upper limit threshold of 10% for side-branch IPMN-associated PDAC was imposed, the model-predicted rate of malignancy for side-branch IPMNs would be less than 0.24% over a 5-year time horizon, substantially lower than most literature-based estimates. Our results suggest that reported malignancy risks associated with side-branch IPMNs are likely to be overestimates and imply the presence of verification bias.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{10.1001/jamanetworkopen.2018.7621,

title = {Prevention of Prescription Opioid Misuse and Projected Overdose Deaths in the United States},

author = {Qiushi Chen and Marc R. Larochelle and Davis Weaver and Anna Lietz and Peter P. Mueller and Sarah Fletcher Mercaldo and Sarah E. Wakeman and Kenneth A. Freedberg and Tiana Raphel and Amy Knudsen and Pari Pandharipande and Jagpreet Chhatwal},

url = {https://dx.doi.org/10.1001/jamanetworkopen.2018.7621},

doi = {10.1001/jamanetworkopen.2018.7621},

issn = {2574-3805},

year  = {2019},

date = {2019-02-01},

journal = {JAMA Network Open},

volume = {2},

number = {2},

pages = {e187621-e187621},

abstract = {Deaths due to opioid overdose have tripled in the last decade. Efforts to curb this trend have focused on restricting the prescription opioid supply; however, the near-term effects of such efforts are unknown.To project effects of interventions to lower prescription opioid misuse on opioid overdose deaths from 2016 to 2025.This system dynamics (mathematical) model of the US opioid epidemic projected outcomes of simulated individuals who engage in nonmedical prescription or illicit opioid use from 2016 to 2025. The analysis was performed in 2018 by retrospectively calibrating the model from 2002 to 2015 data from the National Survey on Drug Use and Health and the Centers for Disease Control and Prevention.Comparison of interventions that would lower the incidence of prescription opioid misuse from 2016 to 2025 based on historical trends (a 7.5% reduction per year) and 50% faster than historical trends (an 11.3% reduction per year), vs a circumstance in which the incidence of misuse remained constant after 2015.Opioid overdose deaths from prescription and illicit opioids from 2016 to 2025 under each intervention.Under the status quo, the annual number of opioid overdose deaths is projected to increase from 33 100 in 2015 to 81 700 (95% uncertainty interval [UI], 63 600-101 700) in 2025 (a 147% increase from 2015). From 2016 to 2025, 700 400 (95% UI, 590 200-817 100) individuals in the United States are projected to die from opioid overdose, with 80% of the deaths attributable to illicit opioids. The number of individuals using illicit opioids is projected to increase by 61%\textemdashfrom 0.93 million (95% UI, 0.83-1.03 million) in 2015 to 1.50 million (95% UI, 0.98-2.22 million) by 2025. Across all interventions tested, further lowering the incidence of prescription opioid misuse from 2015 levels is projected to decrease overdose deaths by only 3.0% to 5.3%.This study’s findings suggest that interventions targeting prescription opioid misuse such as prescription monitoring programs may have a modest effect, at best, on the number of opioid overdose deaths in the near future. Additional policy interventions are urgently needed to change the course of the epidemic.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lietz2019,

title = {Potential survival benefits from optimized chemotherapy implementation in advanced ovarian cancer: Projections from a microsimulation model.},

author = {Anna Lietz and Davis Weaver and Alexander Melamed and Jose Alejandro Rauh-Hain and Jason D Wright and Alexi Wright and Amy Knudsen and Pari Pandharipande},

url = {https://www.ncbi.nlm.nih.gov/pubmed/31539415},

doi = {10.1371/journal.pone.0222828},

issn = {1932-6203},

year  = {2019},

date = {2019-01-01},

journal = {PloS one},

volume = {14},

pages = {e0222828},

abstract = {Ovarian cancer is often diagnosed in advanced stages, when survival is poor. Treatment advances have been made, but are inconsistently implemented. Our purpose was to project the maximum life expectancy gains that could be achieved in women with stage IIIC epithelial ovarian cancer if the implementation of available chemotherapy regimens could be optimized. We used a microsimulation model to estimate life expectancy benefits associated with "optimized" implementation of four post-operative chemotherapy options: standard intravenous chemotherapy; intraperitoneal + intravenous chemotherapy; bevacizumab + intravenous chemotherapy; and hyperthermic intraperitoneal chemotherapy + intravenous chemotherapy. Optimized implementation was defined as follows. Patients triaged to primary cytoreductive surgery received intraperitoneal + intravenous chemotherapy if optimally or completely cytoreduced, and bevacizumab + intravenous chemotherapy if suboptimally cytoreduced. Patients triaged to neoadjuvant chemotherapy received hyperthermic intraperitoneal chemotherapy at interval cytoreductive surgery if optimally or completely cytoreduced, and standard IV chemotherapy if suboptimally cytoreduced. Life expectancy associated with optimized implementation was compared with that of current utilization practices, estimated using published literature and the National Cancer Database. Effects of model uncertainty were evaluated in sensitivity analyses. Life expectancy associated with optimized implementation vs. current practice was 76.7 vs. 64.5 months (life expectancy gain = 12.2 months). Providing intraperitoneal + intravenous chemotherapy to all eligible patients was the largest driver of life expectancy gains, due to both the potential benefit conferred by intraperitoneal + intravenous chemotherapy and the proportion of eligible women who do not receive intraperitoneal + intravenous chemotherapy in current practice. Population-level life expectancy in stage IIIC epithelial ovarian cancer could be substantially improved through greater uptake of available chemotherapy regimens.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Naber2019,

title = {Cost-effectiveness of a multitarget stool DNA test for colorectal cancer screening of Medicare beneficiaries.},

author = {Steffie K Naber and Amy Knudsen and Ann G Zauber and Carolyn M Rutter and Sara E Fischer and Chester J Pabiniak and Brittany Soto and Karen M Kuntz and Iris Lansdorp-Vogelaar},

url = {https://www.ncbi.nlm.nih.gov/pubmed/31483796},

doi = {10.1371/journal.pone.0220234},

issn = {1932-6203},

year  = {2019},

date = {2019-01-01},

journal = {PloS one},

volume = {14},

pages = {e0220234},

abstract = {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. 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. 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. 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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Neal2018,

title = {Patient Navigation to Improve Cancer Screening in Underserved Populations: Reported Experiences, Opportunities, and Challenges},

author = {Chrishanae Neal and Davis Weaver and Tiana Raphel and Anna Lietz and Efren J Flores and Sanja Percac-Lima and Amy Knudsen and Pari Pandharipande},

url = {http://www.ncbi.nlm.nih.gov/pubmed/29685346},

doi = {10.1016/j.jacr.2018.03.001},

issn = {1558-349X},

year  = {2018},

date = {2018-11-01},

journal = {Journal of the American College of Radiology : JACR},

volume = {15},

number = {11},

pages = {1565-1572},

abstract = {Our goal is to define patient navigation for an imaging audience, present a focused selection of published experiences with navigation programs for breast and colorectal cancer screening, and expose principal barriers to the success of such programs. Despite numerous advances in the early detection of cancers, many patients still present with advanced disease. A disproportionate number are low-income minority patients who experience worse health outcomes than their white or more financially stable counterparts. Patient navigation, which aims to assist the medically underserved by overcoming specific barriers to care, may represent one solution to narrowing disparities. Related research suggests that in general, patient navigation programs that have addressed breast or colorectal cancer screening have been successful in improving screening rates and timeliness of follow-up care. However, although beneficial, navigation is expensive and may present an unmanageable financial burden for many health care centers. To overcome this challenge, navigation efforts will likely need to target those patients that are most likely to benefit. Further research to identify such patients will be critically important for improving the sustainability of navigation programs, and, in turn, for realizing the benefits of such programs in reducing cancer disparities.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Meester2018,

title = {Optimizing colorectal cancer screening by race and sex: Microsimulation analysis II to inform the American Cancer Society colorectal cancer screening guideline.},

author = {Reinier G S Meester and Elisabeth F P Peterse and Amy Knudsen and Anne C Weerdt and Jennifer C Chen and Anna Lietz and Andrea Dwyer and Dennis J Ahnen and Rebecca L Siegel and Robert A Smith and Ann G Zauber and Iris Lansdorp-Vogelaar},

url = {http://www.ncbi.nlm.nih.gov/pubmed/29846942},

doi = {10.1002/cncr.31542},

issn = {1097-0142},

year  = {2018},

date = {2018-07-01},

urldate = {2018-07-01},

journal = {Cancer},

volume = {124},

number = {15},

pages = {2974-2985},

abstract = {Colorectal cancer (CRC) risk varies by race and sex. This study, 1 of 2 microsimulation analyses to inform the 2018 American Cancer Society CRC screening guideline, explored the influence of race and sex on optimal CRC screening strategies. Two Cancer Intervention and Surveillance Modeling Network microsimulation models, informed by US incidence data, were used to evaluate a variety of screening methods, ages to start and stop, and intervals for 4 demographic subgroups (black and white males and females) under 2 scenarios for the projected lifetime CRC risk for 40-year-olds: 1) assuming that risk had remained stable since the early screening era and 2) assuming that risk had increased proportionally to observed incidence trends under the age of 40 years. Model-based screening recommendations were based on the predicted level of benefit (life-years gained) and burden (required number of colonoscopies), the incremental burden-to-benefit ratio, and the relative efficiency in comparison with strategies with similar burdens. When lifetime CRC risk was assumed to be stable over time, the models differed in the recommended age to start screening for whites (45 vs 50 years) but consistently recommended screening from the age of 45 years for blacks. When CRC risk was assumed to be increased, the models recommended starting at the age of 45 years, regardless of race and sex. Strategies recommended under both scenarios included colonoscopy every 10 or 15 years, annual fecal immunochemical testing, and computed tomographic colonography every 5 years through the age of 75 years. Microsimulation modeling suggests that CRC screening should be considered from the age of 45 years for blacks and for whites if the lifetime risk has increased proportionally to the incidence for younger adults. Cancer 2018. © 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Weaver2018,

title = {Modeling treatment outcomes for patients with advanced ovarian cancer: Projected benefits of a test to optimize treatment selection.},

author = {Davis Weaver and Tiana Raphel and Alexander Melamed and Jose Alejandro Rauh-Hain and John O Schorge and Amy Knudsen and Pari Pandharipande},

url = {http://www.ncbi.nlm.nih.gov/pubmed/29486993},

doi = {10.1016/j.ygyno.2018.02.007},

issn = {1095-6859},

year  = {2018},

date = {2018-05-01},

journal = {Gynecologic oncology},

volume = {149},

number = {2},

pages = {256-262},

abstract = {For patients with advanced stage epithelial ovarian cancer (EOC), substantial emphasis has been placed on diagnostic tests that can discern which of two treatment options - primary cytoreductive surgery (PCS) or neoadjuvant chemotherapy followed by interval cytoreductive surgery (NACT+ICS) - optimizes patient-level outcomes. Our goal was to project potential life expectancy (LE) gains that could be achieved by use of such a test. We developed a microsimulation model to project LE for patients with stage IIIC EOC. We compared: a "standard-of-care" strategy, in which patients were triaged to PCS vs. NACT+ICS based on current clinical practice; and a "test" strategy, in which patients were triaged based on results of a hypothetical test. We identified those test performance characteristics for which the test strategy outperformed the standard-of-care strategy, from a LE standpoint. Effects of parameter uncertainty were evaluated in sensitivity analysis. Even with a perfect test, the LE gain was modest (LE with test vs. standard-of-care strategy=67.6 vs. 66.4months; LE gain=1.2months). In order to outperform the standard-of-care, the test had to have a high probability of correctly identifying "resectable" patients at PCS (i.e. those for whom complete or optimal cytoreduction would be possible); this test property was more important than correct triage of unresectable patients to NACT+ICS. Results were sensitive to the proportion of patients whose underlying disease was resectable at PCS. Diagnostic tests that are designed to triage patients with advanced stage EOC will likely have only a modest effect on LE.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Raphel2018,

title = {Imaging Follow-up of Low-Risk Incidental Pancreas and Kidney Findings: Effects of Patient Age and Comorbidity on Projected Life Expectancy.},

author = {Tiana Raphel and Davis Weaver and Lincoln L Berland and Brian R Herts and Alec J Megibow and Amy Knudsen and Pari Pandharipande},

url = {https://www.ncbi.nlm.nih.gov/pubmed/29401040},

doi = {10.1148/radiol.2018171701},

issn = {1527-1315},

year  = {2018},

date = {2018-05-01},

urldate = {2018-05-01},

journal = {Radiology},

volume = {287},

number = {2},

pages = {504-514},

abstract = {Purpose To determine the effects of patient age and comorbidity level on life expectancy (LE) benefits associated with imaging follow-up of Bosniak IIF renal cysts and pancreatic side-branch (SB) intraductal papillary mucinous neoplasms (IPMNs). Materials and Methods A decision-analytic Markov model to evaluate LE benefits was developed. Hypothetical cohorts with varied age (60-80 years) and comorbidities (none, mild, moderate, or severe) were evaluated. For each finding, LE projections from two strategies were compared: imaging follow-up and no imaging follow-up. Under follow-up, it was assumed that cancers associated with the incidental finding were successfully treated before they spread. For patients without follow-up, mortality risks from Bosniak IIF cysts (renal cell carcinoma) and SBIPMNs (pancreatic ductal adenocarcinoma) were incorporated. Model assumptions and parameter uncertainty were evaluated in sensitivity analysis. Results In the youngest, healthiest cohorts (age, 60 years; no comorbidities), projected LE benefits from follow-up were as follows: Bosniak IIF cyst, 6.5 months (women) and 5.8 months (men); SBIPMN, 6.4 months (women) and 5.3 months (men). Follow-up of Bosniak IIF cysts in 60-year-old women with severe comorbidities yielded a LE benefit of 3.9 months; in 80-year-old women with no comorbidities, the benefit was 2.8 months, and with severe comorbidities the benefit was 1.5 months. Similar trends were observed in men and for SBIPMN. Results were sensitive to the performance of follow-up for cancer detection; malignancy risks; and stage at presentation of malignant, unfollowed Bosniak IIF cysts. Conclusion With progression of age and comorbidity level, follow-up of low-risk incidental findings yields increasingly limited benefits for patients. © RSNA, 2018 Online supplemental material is available for this article.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Rutter2016,

title = {Validation of Models Used to Inform Colorectal Cancer Screening Guidelines: Accuracy and Implications},

author = {Carolyn M. Rutter and Amy Knudsen and Tracey L. Marsh and V Paul Doria-Rose and Eric Johnson and Chester Pabiniak and Karen M. Kuntz and Marjolein Ballegooijen and Ann G. Zauber and Iris Lansdorp-Vogelaar},

url = {http://www.ncbi.nlm.nih.gov/pubmed/26746432},

doi = {10.1177/0272989X15622642},

year  = {2016},

date = {2016-07-01},

journal = {Med Decis Making},

volume = {36},

number = {5},

pages = {604-14},

institution = {Intervention Research Branch, Bethesda, MD, USA (VPD)Group Health Research Institute, Seattle, WA, USA (EJ, CP)Department of Health Policy and Management, School of Public Health, University of Minnesota, Minneapolis, MN, USA (KMK)Department of Public He},

abstract = {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.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.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.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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Knudsen2016,

title = {Estimation of Benefits, Burden, and Harms of Colorectal Cancer Screening Strategies: Modeling Study for the US Preventive Services Task Force},

author = {Amy Knudsen and Ann G. Zauber and Carolyn M. Rutter and Steffie K. Naber and V Paul Doria-Rose and Chester Pabiniak and Colden Johanson and Sara E. Fischer and Iris Lansdorp-Vogelaar and Karen M. Kuntz},

url = {http://www.ncbi.nlm.nih.gov/pubmed/27305518},

doi = {10.1001/jama.2016.6828},

year  = {2016},

date = {2016-06-01},

urldate = {2016-06-01},

journal = {JAMA},

volume = {315},

number = {23},

pages = {2595--2609},

institution = {Department of Health Policy and Management, School of Public Health, University of Minnesota, Minneapolis.},

abstract = {The US Preventive Services Task Force (USPSTF) is updating its 2008 colorectal cancer (CRC) screening recommendations.To inform the USPSTF by modeling the benefits, burden, and harms of CRC screening strategies; estimating the optimal ages to begin and end screening; and identifying a set of model-recommendable strategies that provide similar life-years gained (LYG) and a comparable balance between LYG and screening burden.Comparative modeling with 3 microsimulation models of a hypothetical cohort of previously unscreened US 40-year-olds with no prior CRC diagnosis.Screening with sensitive guaiac-based fecal occult blood testing, fecal immunochemical testing (FIT), multitarget stool DNA testing, flexible sigmoidoscopy with or without stool testing, computed tomographic colonography (CTC), or colonoscopy starting at age 45, 50, or 55 years and ending at age 75, 80, or 85 years. Screening intervals varied by modality. Full adherence for all strategies was assumed.Life-years gained compared with no screening (benefit), lifetime number of colonoscopies required (burden), lifetime number of colonoscopy complications (harms), and ratios of incremental burden and benefit (efficiency ratios) per 1000 40-year-olds.The screening strategies provided LYG in the range of 152 to 313 per 1000 40-year-olds. Lifetime colonoscopy burden per 1000 persons ranged from fewer than 900 (FIT every 3 years from ages 55-75 years) to more than 7500 (colonoscopy screening every 5 years from ages 45-85 years). Harm from screening was at most 23 complications per 1000 persons screened. Strategies with screening beginning at age 50 years generally provided more LYG as well as more additional LYG per additional colonoscopy than strategies with screening beginning at age 55 years. There were limited empirical data to support a start age of 45 years. For persons adequately screened up to age 75 years, additional screening yielded small increases in LYG relative to the increase in colonoscopy burden. With screening from ages 50 to 75 years, 4 strategies yielded a comparable balance of screening burden and similar LYG (median LYG per 1000 across the models): colonoscopy every 10 years (270 LYG); sigmoidoscopy every 10 years with annual FIT (256 LYG); CTC every 5 years (248 LYG); and annual FIT (244 LYG).In this microsimulation modeling study of a previously unscreened population undergoing CRC screening that assumed 100% adherence, the strategies of colonoscopy every 10 years, annual FIT, sigmoidoscopy every 10 years with annual FIT, and CTC every 5 years performed from ages 50 through 75 years provided similar LYG and a comparable balance of benefit and screening burden.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Goede2015,

title = {Cost-Savings to Medicare From Pre-Medicare Colorectal Cancer Screening},

author = {Simon L. Goede and Karen M. Kuntz and Marjolein Ballegooijen and Amy Knudsen and Iris Lansdorp-Vogelaar and Florence K. Tangka and David H. Howard and Joseph Chin and Ann G. Zauber and Laura C. Seeff},

url = {http://www.ncbi.nlm.nih.gov/pubmed/26067885},

doi = {10.1097/MLR.0000000000000380},

year  = {2015},

date = {2015-07-01},

journal = {Med Care},

volume = {53},

number = {7},

pages = {630--638},

institution = {*Department of Public Health, Erasmus University Medical Center, Rotterdam, The Netherlands †Division of Health Policy and Management, University of Minnesota, Minneapolis, MN ‡Department of Radiology, Institute for Technology Assessment, Massachusetts Ge},

abstract = {Many individuals have not received recommended colorectal cancer (CRC) screening before they become Medicare eligible at the age of 65. We aimed to estimate the long-term implications of increased CRC screening in the pre-Medicare population (50-64 y) on costs in the pre-Medicare and Medicare populations (65+ y).We used 2 independently developed microsimulation models [Microsimulation Screening Analysis Colon (MISCAN) and Simulation Model of CRC (SimCRC)] to project CRC screening and treatment costs under 2 scenarios, starting in 2010: "current trends" (60% of the population up-to-date with screening recommendations) and "enhanced participation" (70% up-to-date). The population was scaled to the projected US population for each year between 2010 and 2060. Costs per year were derived by age group (50-64 and 65+ y).By 2060, the discounted cumulative total costs in the pre-Medicare population were $35.7 and $28.1 billion higher with enhanced screening participation, than in the current trends scenario ($252.1 billion with MISCAN and $239.5 billion with SimCRC, respectively). Because of CRC treatment savings with enhanced participation, cumulative costs in the Medicare population were $18.3 and $32.7 billion lower (current trends: $423.5 billion with MISCAN and $372.8 billion with SimCRC). Over the 50-year time horizon an estimated 60% (MISCAN) and 89% (SimCRC) of the increased screening costs could be offset by savings in Medicare CRC treatment costs.Increased CRC screening participation in the pre-Medicare population could reduce CRC incidence and mortality, whereas the additional screening costs can be largely offset by long-term Medicare treatment savings.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{vanderSteen2015,

title = {Optimal colorectal cancer screening in states' low-income, uninsured populations-the case of South Carolina},

author = {Alex Steen and Amy Knudsen and Frank Hees and Gailya P. Walter and Franklin G. Berger and Virginie G. Daguise and Karen M. Kuntz and Ann G. Zauber and Marjolein Ballegooijen and Iris Lansdorp-Vogelaar},

url = {http://www.ncbi.nlm.nih.gov/pubmed/25324198},

doi = {10.1111/1475-6773.12246},

year  = {2015},

date = {2015-06-01},

urldate = {2015-06-01},

journal = {Health Serv Res},

volume = {50},

number = {3},

pages = {768--789},

institution = {Department of Public Health, Erasmus MC, Rotterdam, The Netherlands.},

abstract = {To determine whether, given a limited budget, a state's low-income uninsured population would have greater benefit from a colorectal cancer (CRC) screening program using colonoscopy or fecal immunochemical testing (FIT).South Carolina's low-income, uninsured population.Comparative effectiveness analysis using microsimulation modeling to estimate the number of individuals screened, CRC cases prevented, CRC deaths prevented, and life-years gained from a screening program using colonoscopy versus a program using annual FIT in South Carolina's low-income, uninsured population. This analysis assumed an annual budget of $1 million and a budget availability of 2 years as a base case.The annual FIT screening program resulted in nearly eight times more individuals being screened, and more important, approximately four times as many CRC deaths prevented and life-years gained than the colonoscopy screening program. Our results were robust for assumptions concerning economic perspective and the target population, and they may therefore be generalized to other states and populations.A FIT screening program will prevent more CRC deaths than a colonoscopy-based program when a state's budget for CRC screening supports screening of only a fraction of the target population.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Rutter2013,

title = {Secular Trends in Colon and Rectal Cancer Relative Survival},

author = {Carolyn M. Rutter and Eric A. Johnson and Eric J. Feuer and Amy Knudsen and Karen M. Kuntz and Deborah Schrag},

url = {http://www.ncbi.nlm.nih.gov/pubmed/24174654},

doi = {10.1093/jnci/djt299},

year  = {2013},

date = {2013-12-01},

urldate = {2013-12-01},

journal = {J Natl Cancer Inst},

volume = {105},

number = {23},

pages = {1806-13},

institution = {Affiliations of authors: Group Health Research Institute, Seattle, WA (CMR, EAJ); Division of Cancer Control and Population Sciences National Cancer Institute, Bethesda, MD (EJF); Institute for Technology Assessment, Department of Radiology, Massach},

abstract = {Treatment options for colorectal cancer (CRC) have improved substantially 

	over the past 25 years. Measuring the impact of these improvements 

	on survival outcomes is challenging, however, against the background 

	of overall survival gains from advancements in the prevention, screening, 

	and treatment of other conditions. Relative survival is a metric 

	that accounts for these concurrent changes, allowing assessment of 

	changes in CRC survival. We describe stage- and location-specific 

	trends in relative survival after CRC diagnosis.We analyzed survival 

	outcomes for 233965 people in the Surveillance Epidemiology and End 

	Results (SEER) program who were diagnosed with CRC between January 

	1, 1975, and December 31, 2003. All models were adjusted for sex, 

	race (black vs white), age at diagnosis, time since diagnosis, and 

	diagnosis year. We estimated the proportional difference in survival 

	for CRC patients compared with overall survival for age-, sex-, race-, 

	and period-matched controls to account for concurrent changes in 

	overall survival using two-sided Wald tests.We found statistically 

	significant reductions in excess hazard of mortality from CRC in 

	2003 relative to 1975, with excess hazard ratios ranging from 0.75 

	(stage IV colon cancer; P},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Knudsen2012,

title = {Rescreening of persons with a negative colonoscopy result: results	from a microsimulation model},

author = {Amy Knudsen and Chin Hur and G. Scott Gazelle and Deborah Schrag and Elizabeth G. McFarland and Karen M. Kuntz},

url = {http://www.ncbi.nlm.nih.gov/pubmed/23128861},

doi = {10.7326/0003-4819-157-9-201211060-00005},

year  = {2012},

date = {2012-11-01},

journal = {Ann Intern Med},

volume = {157},

number = {9},

pages = {611--620},

abstract = {Persons with a negative result on screening colonoscopy are recommended to repeat the procedure in 10 years.To assess the effectiveness and costs of colonoscopy versus other rescreening strategies after an initial negative colonoscopy result.Microsimulation model.Literature and data from the Surveillance, Epidemiology, and End Results program.Persons aged 50 years who had no adenomas or cancer detected on screening colonoscopy.Lifetime.Societal.No further screening or rescreening starting at age 60 years with colonoscopy every 10 years, annual highly sensitive guaiac fecal occult blood testing (HSFOBT), annual fecal immunochemical testing (FIT), or computed tomographic colonography (CTC) every 5 years.Lifetime cases of colorectal cancer, life expectancy, and lifetime costs per 1000 persons, assuming either perfect or imperfect adherence.Rescreening with any method substantially reduced the risk for colorectal cancer compared with no further screening (range, 7.7 to 12.6 lifetime cases per 1000 persons [perfect adherence] and 17.7 to 20.9 lifetime cases per 1000 persons [imperfect adherence] vs. 31.3 lifetime cases per 1000 persons with no further screening). 

 

In both adherence scenarios, the differences in life-years across rescreening strategies were small (range, 30 893 to 30 902 life-years per 1000 persons [perfect adherence] vs. 30 865 to 30 869 life-years per 1000 persons [imperfect adherence]). Rescreening with HSFOBT, FIT, or CTC had fewer complications and was less costly than continuing colonoscopy.Results were sensitive to test-specific adherence rates.Data on adherence to rescreening were limited.Compared with the currently recommended strategy of continuing colonoscopy every 10 years after an initial negative examination, rescreening at age 60 years with annual HSFOBT, annual FIT, or CTC every 5 years provides approximately the same benefit in life-years with fewer complications at a lower cost. Therefore, it is reasonable to use other methods to rescreen persons with negative colonoscopy results.National Cancer Institute.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Vanness2011,

title = {Comparative economic evaluation of data from the ACRIN National CT 

	Colonography {T}rial with three cancer intervention and surveillance 

	modeling network microsimulations},

author = {D. J. Vanness and Amy Knudsen and I. Lansdorp-Vogelaar and C. M. Rutter and I. F. Gareen and B. A. Herman and K. M. Kuntz and A. G. Zauber and M. Ballegooijen and E. J. Feuer and M. H. Chen and C. D. Johnson},

url = {http://www.ncbi.nlm.nih.gov/pubmed/21813740},

issn = {1527-1315 (Electronic) 0033-8419},

year  = {2011},

date = {2011-11-01},

journal = {Radiology},

volume = {261},

number = {2},

pages = {487-98},

abstract = {PURPOSE: To estimate the cost-effectiveness of computed tomographic 

	(CT) colonography for colorectal cancer (CRC) screening in average-risk 

	asymptomatic subjects in the United States aged 50 years. MATERIALS 

	AND METHODS: Enrollees in the American College of Radiology Imaging 

	Network National CT Colonography Trial provided informed consent, 

	and approval was obtained from the institutional review board at 

	each site. CT colonography performance estimates from the trial were 

	incorporated into three Cancer Intervention and Surveillance Modeling 

	Network CRC microsimulations. Simulated survival and lifetime costs 

	for screening 50-year-old subjects in the United States with CT colonography 

	every 5 or 10 years were compared with those for guideline-concordant 

	screening with colonoscopy, flexible sigmoidoscopy plus either sensitive 

	unrehydrated fecal occult blood testing (FOBT) or fecal immunochemical 

	testing (FIT), and no screening. Perfect and reduced screening adherence 

	scenarios were considered. Incremental cost-effectiveness and net 

	health benefits were estimated from the U.S. health care sector perspective, 

	assuming a 3% discount rate. RESULTS: CT colonography at 5- and 10-year 

	screening intervals was more costly and less effective than FOBT 

	plus flexible sigmoidoscopy in all three models in both 100% and 

	50% adherence scenarios. Colonoscopy also was more costly and less 

	effective than FOBT plus flexible sigmoidoscopy, except in the CRC-SPIN 

	model assuming 100% adherence (incremental cost-effectiveness ratio: 

	$26,300 per life-year gained). CT colonography at 5- and 10-year 

	screening intervals and colonoscopy were net beneficial compared 

	with no screening in all model scenarios. The 5-year screening interval 

	was net beneficial over the 10-year interval except in the MISCAN 

	model when assuming 100% adherence and willingness to pay $50,000 

	per life-year gained. CONCLUSION: All three models predict CT colonography 

	to be more costly and less effective than non-CT colonographic screening 

	but net beneficial compared with no screening given model assumptions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Rutter2011,

title = {Computer disease simulation models: integrating evidence for health 

	policy},

author = {C. M. Rutter and Amy Knudsen and Pari Pandharipande},

url = {http://www.ncbi.nlm.nih.gov/pubmed/21435924},

issn = {1878-4046 (Electronic) 1076-6332},

year  = {2011},

date = {2011-09-01},

journal = {Acad Radiol},

volume = {18},

number = {9},

pages = {1077-86},

abstract = {Computer disease simulation models are increasingly being used to 

	evaluate and inform health care decisions across medical disciplines. 

	The aim of researchers who develop these models is to integrate and 

	synthesize short-term outcomes and results from multiple sources 

	to predict the long-term clinical outcomes and costs of different 

	health care strategies. Policy makers, in turn, can use the predictions 

	generated by disease models together with other evidence to make 

	decisions related to health care practices and resource utilization. 

	Models are particularly useful when the existing evidence does not 

	yield obvious answers or does not provide answers to the questions 

	of greatest interest, such as questions about the relative cost-effectiveness 

	of different practices. This review focuses on models used to inform 

	decisions about imaging technology, discussing the role of disease 

	models for health policy development and providing a foundation for 

	understanding the basic principles of disease modeling. This manuscript 

	draws from the collective computed tomographic colonography modeling 

	experience, reviewing 10 published investigations of the clinical 

	effectiveness and cost-effectiveness of computed tomographic colonography 

	relative to colonoscopy. The discussion focuses on implications of 

	different modeling assumptions and difficulties that may be encountered 

	when evaluating the quality of models. This underscores the importance 

	of forging stronger collaborations between researchers who develop 

	disease models and radiologists, to ensure that policy-level models 

	accurately represent the experience of everyday clinical practices.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lansdorp-Vogelaar2011,

title = {Cost-effectiveness of colorectal cancer screening},

author = {I. Lansdorp-Vogelaar and Amy Knudsen and H. Brenner},

url = {http://www.ncbi.nlm.nih.gov/pubmed/21633092},

issn = {1478-6729 (Electronic) 0193-936X},

year  = {2011},

date = {2011-07-01},

journal = {Epidemiol Rev},

volume = {33},

number = {1},

pages = {88-100},

abstract = {Colorectal cancer is an important public health problem. Several screening 

	methods have been shown to be effective in reducing colorectal cancer 

	mortality. The objective of this review was to assess the cost-effectiveness 

	of the different colorectal cancer screening methods and to determine 

	the preferred method from a cost-effectiveness point of view. Five 

	databases (MEDLINE, EMBASE, the Cost-Effectiveness Analysis Registry, 

	the British National Health Service Economic Evaluation Database, 

	and the lists of technology assessments of the Centers for Medicare 

	and Medicaid Services) were searched for cost-effectiveness analyses 

	published in English between January 1993 and December 2009. Fifty-five 

	publications relating to 32 unique cost-effectiveness models were 

	identified. All studies found that colorectal cancer screening was 

	cost-effective or even cost-saving compared with no screening. However, 

	the studies disagreed as to which screening method was most effective 

	or had the best incremental cost-effectiveness ratio for a given 

	willingness to pay per life-year gained. There was agreement among 

	studies that the newly developed screening tests of stool DNA testing, 

	computed tomographic colonography, and capsule endoscopy were not 

	yet cost-effective compared with the established screening options.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Haug2011,

title = {Sensitivity of immunochemical faecal occult blood testing for detecting 

	left- vs right-sided colorectal neoplasia},

author = {U. Haug and K. M. Kuntz and Amy Knudsen and S. Hundt and H. Brenner},

url = {http://www.ncbi.nlm.nih.gov/pubmed/21559011},

issn = {1532-1827 (Electronic) 0007-0920},

year  = {2011},

date = {2011-05-01},

journal = {Br J Cancer},

volume = {104},

number = {11},

pages = {1779-85},

abstract = {BACKGROUND: Faecal occult blood tests (FOBTs) are used for colorectal 

	cancer (CRC) screening. We aimed to assess the sensitivity of an 

	immunochemical FOBT for detecting advanced colorectal neoplasia in 

	the left vs the right colon and to explore reasons for potential 

	differences in site-specific test performance. METHODS: We prospectively 

	measured faecal occult blood levels by a quantitative immunochemical 

	FOBT (RIDASCREEN) in 2310 average-risk subjects undergoing screening 

	colonoscopy. We compared diagnostic performance for subjects with 

	left- vs right-sided advanced neoplasia, as well as patient characteristics 

	and adenoma characteristics that have been suggested to impact faecal 

	haemoglobin levels. RESULTS: Sensitivities for subjects with left- 

	vs right-sided advanced neoplasia were 33% (95% confidence interval (CI), 26-41%) and 20% (CI, 11-31%) (P=0.04) at a specificity of 95% 

	(overall sensitivity: 29%) and the areas under the receiver-operating 

	characteristics curve were 0.71 (CI, 0.69-0.72) and 0.60 (CI, 0.58-0.63), 

	respectively. Pedunculated shape was strikingly more common in participants 

	with left- vs right-sided advanced neoplasia (47% vs 14%). In logistic 

	regression analyses adjusted for site, pedunculated shape was statistically significantly associated with test sensitivity (P=0.04). CONCLUSIONS: 

	The immunochemical FOBT in our study was more sensitive for detecting 

	subjects with left- vs right-sided advanced colorectal neoplasia. 

	Our findings may stimulate further diagnostic research in the field 

	as well as modelling analyses to estimate the potential effect of 

	site-specific test performance on the effectiveness of annual or 

	biennial FOBT-based screening programmes, in particular with respect 

	to protection from right-sided CRC.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gonzalez2011,

title = {Radiation-related cancer risks from CT colonography screening: a 

	risk-benefit analysis},

author = {A. Berrington Gonzalez and K. P. Kim and Amy Knudsen and I. Lansdorp-Vogelaar and C. M. Rutter and R. Smith-Bindman and J. Yee and K. M. Kuntz and M. Ballegooijen and A. G. Zauber and C. D. Berg},

url = {http://www.ncbi.nlm.nih.gov/pubmed/21427330},

issn = {1546-3141 (Electronic) 0361-803X},

year  = {2011},

date = {2011-04-01},

journal = {AJR Am J Roentgenol},

volume = {196},

number = {4},

pages = {816-23},

abstract = {OBJECTIVE: The purpose of this study was to estimate the ratio of 

	cancers prevented to induced (benefit-risk ratio) for CT colonography 

	(CTC) screening every 5 years from the age of 50 to 80 years. MATERIALS 

	AND METHODS: Radiation-related cancer risk was estimated using risk 

	projection models based on the National Research Council's Biological 

	Effects of Ionizing Radiation (BEIR) VII Committee's report and screening 

	protocols from the American College of Radiology Imaging Network's 

	National CT Colonography Trial. Uncertainty intervals were estimated 

	using Monte Carlo simulation methods. Comparative modeling with three 

	colorectal cancer microsimulation models was used to estimate the 

	potential reduction in colorectal cancer cases and deaths. RESULTS: 

	The estimated mean effective dose per CTC screening study was 8 mSv 

	for women and 7 mSv for men. The estimated number of radiation-related 

	cancers resulting from CTC screening every 5 years from the age of 

	50 to 80 years was 150 cases/100,000 individuals screened (95% uncertainty 

	interval, 80-280) for men and women. The estimated number of colorectal 

	cancers prevented by CTC every 5 years from age 50 to 80 ranged across 

	the three microsimulation models from 3580 to 5190 cases/100,000 

	individuals screened, yielding a benefit-risk ratio that varied from 

	24:1 (95% uncertainty interval, 13:1-45:1) to 35:1 (19:1-65:1). The 

	benefit-risk ratio for cancer deaths was even higher than the ratio 

	for cancer cases. Inclusion of radiation-related cancer risks from 

	CT examinations performed to follow up extracolonic findings did 

	not materially alter the results. CONCLUSION: Concerns have been 

	raised about recommending CTC as a routine screening tool because 

	of potential harms including the radiation risks. Based on these 

	models, the benefits from CTC screening every 5 years from the age 

	of 50 to 80 years clearly outweigh the radiation risks.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Stock2011,

title = {Colorectal cancer mortality prevented by use and attributable to 

	nonuse of colonoscopy},

author = {C. Stock and Amy Knudsen and I. Lansdorp-Vogelaar and U. Haug and H. Brenner},

url = {http://www.ncbi.nlm.nih.gov/pubmed/21353840},

year  = {2011},

date = {2011-01-01},

journal = {Gastrointest Endosc},

volume = {73},

pages = {435-443 e5},

abstract = {BACKGROUND: Use of colonoscopy is thought to reduce colorectal cancer 

	(CRC) mortality, but its impact at the population level is unclear. 

	OBJECTIVE: To estimate the effect of current colonoscopy use on CRC 

	mortality and its further potential in reducing CRC mortality. DESIGN: 

	Population-level analysis was performed by using the concepts of 

	prevented and attributable fractions, by using data from the National 

	Health Interview Survey, the Surveillance, Epidemiology and End Results 

	Program, and estimates of the effectiveness of colonoscopy at reducing 

	CRC mortality. SETTING: The 2005 U.S. population aged 50 years and 

	older. EXPOSURE: Colonoscopy within 10 years or less. MAIN OUTCOME 

	MEASUREMENTS: Percentages and absolute numbers of CRC deaths prevented 

	and potentially preventable by colonoscopy. LIMITATIONS: Uncertainty 

	in effectiveness estimates. RESULTS: Overall, the proportions of 

	CRC deaths in 2005 prevented by colonoscopy (ie, the prevented fractions) 

	range from 13% (95% CI, 1115 to 19% (95% CI, 1224 across the estimates 

	of colonoscopy effectiveness. Corresponding numbers of CRC deaths 

	prevented range from 7314 (95% CI, 6010-8467) to 11,711 (95% CI, 

	7077-14,898). The proportions of CRC deaths attributable to nonuse 

	of colonoscopy (ie, the attributable fractions) range from 28% (95% 

	CI, 2233 to 44% (95% CI, 2460, depending on the assumed effectiveness. 

	Corresponding numbers of CRC deaths attributed to nonuse of colonoscopy 

	range from 13,796 (95% CI, 11,076-16,255) to 22,088 (95% CI, 12,189-29,947). 

	CONCLUSIONS: Although we estimate that colonoscopy has prevented 

	substantial numbers of CRC deaths, many more deaths could have been 

	prevented with more widespread use. These findings highlight the 

	potential benefits from public health interventions to increase the 

	use of screening colonoscopy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ballegooijen2011,

title = {Clarifying differences in natural history between models of screening: 

	the case of colorectal cancer},

author = {M. Ballegooijen and C. M. Rutter and Amy Knudsen and A. G. Zauber and J. E. Savarino and I. Lansdorp-Vogelaar and R. Boer and E. J. Feuer and J. D. Habbema and K. M. Kuntz},

url = {http://www.ncbi.nlm.nih.gov/pubmed/21673187},

year  = {2011},

date = {2011-01-01},

journal = {Med Decis Making},

volume = {31},

pages = {540-9},

abstract = {BACKGROUND: Microsimulation models are important decision support 

	tools for screening. However, their complexity makes them difficult 

	to understand and limits realization of their full potential. Therefore, 

	it is important to develop documentation that clarifies their structure 

	and assumptions. The authors demonstrate this problem and explore 

	a solution for natural history using 3 independently developed colorectal 

	cancer screening models. METHODS: The authors first project effectiveness 

	and cost-effectiveness of colonoscopy screening for the 3 models 

	(CRC-SPIN, SimCRC, and MISCAN). Next, they provide a conventional 

	presentation of each model, including information on structure and 

	parameter values. Finally, they report the simulated reduction in 

	clinical cancer incidence following a one-time complete removal of 

	adenomas and preclinical cancers for each model. They call this new 

	measure the maximum clinical incidence reduction (MCLIR). RESULTS: 

	Projected effectiveness varies widely across models. For example, 

	estimated mortality reduction for colonoscopy screening every 10 

	years from age 50 to 80 years, with surveillance in adenoma patients, 

	ranges from 65% to 92 Given only conventional information, it is 

	difficult to explain these differences, largely because differences 

	in structure make parameter values incomparable. In contrast, the 

	MCLIR clearly shows the impact of model differences on the key feature 

	of natural history, the dwell time of preclinical disease. Dwell 

	times vary from 8 to 25 years across models and help explain differences 

	in projected screening effectiveness. CONCLUSIONS: The authors propose 

	a new measure, the MCLIR, which summarizes the implications for predicted 

	screening effectiveness of differences in natural history assumptions. 

	Including the MCLIR in the standard description of a screening model 

	would improve the transparency of these models.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kuntz2011,

title = {A systematic comparison of microsimulation models of colorectal cancer: the role of assumptions about adenoma progression},

author = {K. M. Kuntz and I. Lansdorp-Vogelaar and C. M. Rutter and Amy Knudsen and M. Ballegooijen and J. E. Savarino and E. J. Feuer and A. G. Zauber},

url = {http://www.ncbi.nlm.nih.gov/pubmed/21673186},

year  = {2011},

date = {2011-01-01},

urldate = {2011-01-01},

journal = {Med Decis Making},

volume = {31},

pages = {530-9},

abstract = {BACKGROUND: As the complexity of microsimulation models increases, 

	concerns about model transparency are heightened. METHODS: The authors 

	conducted model "experiments" to explore the impact of variations 

	in "deep" model parameters using 3 colorectal cancer (CRC) models. 

	All natural history models were calibrated to match observed data 

	on adenoma prevalence and cancer incidence but varied in their underlying 

	specification of the adenocarcinoma process. The authors projected 

	CRC incidence among individuals with an underlying adenoma or preclinical 

	cancer v. those without any underlying condition and examined the 

	impact of removing adenomas. They calculated the percentage of simulated 

	CRC cases arising from adenomas that developed within 10 or 20 years 

	prior to cancer diagnosis and estimated dwell time-defined as the 

	time from the development of an adenoma to symptom-detected cancer 

	in the absence of screening among individuals with a CRC diagnosis. 

	RESULTS: The 20-year CRC incidence among 55-year-old individuals 

	with an adenoma or preclinical cancer was 7 to 75 times greater than 

	in the condition-free group. The removal of all adenomas among the 

	subgroup with an underlying adenoma or cancer resulted in a reduction 

	of 30% to 89% in cumulative incidence. Among CRCs diagnosed at age 

	65 years, the proportion arising from adenomas formed within 10 years 

	ranged between 4% and 67 The mean dwell time varied from 10.6 to 

	25.8 years. CONCLUSIONS: Models that all match observed data on adenoma 

	prevalence and cancer incidence can produce quite different dwell 

	times and very different answers with respect to the effectiveness 

	of interventions. When conducting applied analyses to inform policy, 

	using multiple models provides a sensitivity analysis on key (unobserved) 

	"deep" model parameters and can provide guidance about specific areas 

	in need of additional research and validation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{haug_is_2011,

title = {Is fecal occult blood testing more sensitive for left- versus right-sided colorectal neoplasia? A systematic literature review},

author = {U. Haug and Amy Knudsen and H. Brenner and K. M. Kuntz},

url = {http://www.ncbi.nlm.nih.gov/pubmed/21745014},

doi = {Research Support, Non-U.S. Gov't Review},

issn = {1744-8352 (Electronic) 1473-7159},

year  = {2011},

date = {2011-01-01},

urldate = {2011-01-01},

journal = {Expert Rev Mol Diagn},

volume = {11},

pages = {605--16},

abstract = {Owing to its slow development from removable precursor lesions and early cancer stages with good prognosis, screening for colorectal cancer holds potential to reduce both the incidence and mortality of the disease. While sigmoidoscopy only detects left-sided neoplasia, there is accumulating evidence that colonoscopy is also more effective in protecting from neoplasia in the left versus the right colon and rectum. In this context, it is an important question whether the sensitivity of the most common noninvasive screening tool for colorectal cancer, fecal occult blood testing (FOBT), also differs for left- versus right-sided neoplasia. Therefore, we systematically searched the literature for prospective screening studies conducted in average-risk adults that performed FOBT (immunochemical and/or guaiac-based) and colonoscopy among all participants, and reported site-specific sensitivities of FOBT for advanced colorectal neoplasia. Most of the seven included studies showed a higher sensitivity of FOBT for advanced neoplasia in the left versus right colon, but this finding needs to be confirmed since the available literature is scarce and not entirely consistent.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lansdorp-Vogelaar2010,

title = {Stool DNA testing to screen for colorectal cancer in the Medicare 

	population: a cost-effectiveness analysis},

author = {I. Lansdorp-Vogelaar and K. M. Kuntz and Amy Knudsen and J. A. Wilschut and A. G. Zauber and M. Ballegooijen},

url = {http://www.ncbi.nlm.nih.gov/pubmed/20855801},

issn = {1539-3704 (Electronic) 0003-4819},

year  = {2010},

date = {2010-09-01},

journal = {Ann Intern Med},

volume = {153},

number = {6},

pages = {368-77},

abstract = {BACKGROUND: The Centers for Medicare \& Medicaid Services considered 

	whether to reimburse stool DNA testing for colorectal cancer screening 

	among Medicare enrollees. OBJECTIVE: To evaluate the conditions under 

	which stool DNA testing could be cost-effective compared with the 

	colorectal cancer screening tests currently reimbursed by the Centers 

	for Medicare \& Medicaid Services. DESIGN: Comparative microsimulation 

	modeling study using 2 independently developed models. DATA SOURCES: 

	Derived from literature. TARGET POPULATION: A cohort of persons aged 

	65 years. A sensitivity analysis was also conducted, in which a cohort 

	of persons aged 50 years was studied. TIME HORIZON: Lifetime. Perspective: 

	Third-party payer. Intervention: Stool DNA test every 3 or 5 years 

	in comparison with currently recommended colorectal cancer screening 

	strategies. OUTCOME MEASURES: Life expectancy, lifetime costs, incremental 

	cost-effectiveness ratios, and threshold costs. RESULTS OF BASE-CASE 

	ANALYSIS: Assuming a cost of $350 per test, strategies of stool DNA 

	testing every 3 or 5 years yielded fewer life-years and higher costs 

	than the currently recommended colorectal cancer screening strategies. 

	Screening with the stool DNA test would be cost-effective at a per-test 

	cost of $40 to $60 for stool DNA testing every 3 years, depending 

	on the simulation model used. There were no levels of sensitivity 

	and specificity for which stool DNA testing would be cost-effective 

	at its current cost of $350 per test. Stool DNA testing every 3 years 

	would be cost-effective at a cost of $350 per test if the relative 

	adherence to stool DNA testing were at least 50% better than that 

	with other screening tests. RESULTS OF SENSITIVITY ANALYSIS: None 

	of the results changed substantially when a cohort of persons aged 

	50 years was considered. LIMITATION: No pathways other than the traditional 

	adenoma-carcinoma sequence were modeled. CONCLUSION: Stool DNA testing 

	could be a cost-effective alternative for colorectal cancer screening 

	if the cost of the test substantially decreased or if its availability 

	would entice a large fraction of otherwise unscreened persons to 

	receive screening.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Knudsen2010,

title = {Cost-effectiveness of computed tomographic colonography screening 

	for colorectal cancer in the medicare population},

author = {Amy Knudsen and I. Lansdorp-Vogelaar and C. M. Rutter and J. E. Savarino and M. Ballegooijen and K. M. Kuntz and A. G. Zauber},

url = {http://www.ncbi.nlm.nih.gov/pubmed/20664028},

issn = {1460-2105 (Electronic) 0027-8874},

year  = {2010},

date = {2010-08-01},

journal = {J Natl Cancer Inst},

volume = {102},

number = {16},

pages = {1238-52},

abstract = {BACKGROUND: The Centers for Medicare and Medicaid Services (CMS) considered 

	whether to reimburse computed tomographic colonography (CTC) for 

	colorectal cancer screening of Medicare enrollees. To help inform 

	its decision, we evaluated the reimbursement rate at which CTC screening 

	could be cost-effective compared with the colorectal cancer screening 

	tests that are currently reimbursed by CMS and are included in most 

	colorectal cancer screening guidelines, namely annual fecal occult 

	blood test (FOBT), flexible sigmoidoscopy every 5 years, flexible 

	sigmoidoscopy every 5 years in conjunction with annual FOBT, and 

	colonoscopy every 10 years. METHODS: We used three independently 

	developed microsimulation models to assess the health outcomes and 

	costs associated with CTC screening and with currently reimbursed 

	colorectal cancer screening tests among the average-risk Medicare 

	population. We assumed that CTC was performed every 5 years (using 

	test characteristics from either a Department of Defense CTC study 

	or the National CTC Trial) and that individuals with findings of 

	6 mm or larger were referred to colonoscopy. We computed incremental 

	cost-effectiveness ratios for the currently reimbursed screening 

	tests and calculated the maximum cost per scan (ie, the threshold 

	cost) for the CTC strategy to lie on the efficient frontier. Sensitivity 

	analyses were performed on key parameters and assumptions. RESULTS: 

	Assuming perfect adherence with all tests, the undiscounted number 

	life-years gained from CTC screening ranged from 143 to 178 per 1000 

	65-year-olds, which was slightly less than the number of life-years 

	gained from 10-yearly colonoscopy (152-185 per 1000 65-year-olds) 

	and comparable to that from 5-yearly sigmoidoscopy with annual FOBT 

	(149-177 per 1000 65-year-olds). If CTC screening was reimbursed 

	at $488 per scan (slightly less than the reimbursement for a colonoscopy 

	without polypectomy), it would be the most costly strategy. CTC screening 

	could be cost-effective at $108-$205 per scan, depending on the microsimulation 

	model used. Sensitivity analyses showed that if relative adherence 

	to CTC screening was 25% higher than adherence to other tests, it 

	could be cost-effective if reimbursed at $488 per scan. CONCLUSIONS: 

	CTC could be a cost-effective option for colorectal cancer screening 

	among Medicare enrollees if the reimbursement rate per scan is substantially 

	less than that for colonoscopy or if a large proportion of otherwise 

	unscreened persons were to undergo screening by CTC.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lansdorp-Vogelaar2010a,

title = {Cost-effectiveness of colorectal cancer screening - an overview},

author = {I. Lansdorp-Vogelaar and Amy Knudsen and H. Brenner},

url = {http://www.ncbi.nlm.nih.gov/pubmed/20833348},

issn = {1532-1916 (Electronic) 1521-6918},

year  = {2010},

date = {2010-08-01},

journal = {Best Pract Res Clin Gastroenterol},

volume = {24},

number = {4},

pages = {439-49},

abstract = {There are several modalities available for a colorectal cancer (CRC) 

	screening program. When determining which CRC screening program to 

	implement, the costs of such programs should be considered in comparison 

	to the health benefits they are expected to provide. Cost-effectiveness 

	analysis provides a tool to do this. In this paper we review the 

	evidence on the cost-effectiveness of CRC screening. Published studies 

	universally indicate that when compared with no CRC screening, all 

	screening modalities provide additional years of life at a cost that 

	is deemed acceptable by most industrialized nations. Many recent 

	studies even find CRC screening to be cost-saving. However, when 

	the alternative CRC screening strategies are compared against each 

	other in an incremental cost-effectiveness analysis, no single optimal 

	strategy emerges across the studies. There is consensus that the 

	new technologies of stool DNA testing, computed tomographic colonography 

	and capsule endoscopy are not yet cost-effective compared with the 

	established CRC screening tests.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Greenblatt2009,

title = {Cost-effectiveness of prophylactic surgery for duodenal cancer in 

	familial adenomatous polyposis},

author = {Wesley Greenblatt and Chin Hur and Amy Knudsen and J. A. Evans and D. C. Chung and G. Scott Gazelle},

url = {http://www.ncbi.nlm.nih.gov/pubmed/19789369},

issn = {1538-7755 (Electronic) 1055-9965},

year  = {2009},

date = {2009-10-01},

journal = {Cancer Epidemiol Biomarkers Prev},

volume = {18},

number = {10},

pages = {2677-84},

abstract = {BACKGROUND: Duodenal cancer is the leading cause of cancer death in 

	familial adenomatous polyposis after colorectal cancer. The lifetime 

	risk for developing duodenal cancer is 4% to 10%. Current treatment 

	guidelines recommend endoscopic surveillance with a prophylactic 

	pancreaticoduodenectomy in advanced duodenal polyposis, defined using 

	the Spigelman staging system. Because no clinical trials have assessed 

	this recommendation, a modeling approach was used to evaluate the 

	cost-effectiveness of various treatment strategies. METHODS: A Markov 

	model was constructed to estimate the life expectancy and cost of 

	three different strategies: pancreaticoduodenectomy at Spigelman 

	stage III, pancreaticoduodenectomy at Spigelman stage IV, and pancreaticoduodenectomy 

	at cancer diagnosis. A cohort of 30-year-old familial adenomatous 

	polyposis patients with total colectomies was simulated until age 

	80. The analysis was from a societal perspective. Extensive sensitivity 

	analysis was performed to assess the impact of model uncertainty 

	on results. RESULTS: At all stages of polyposis and all ages \<80 

	years, prophylactic surgery at Spigelman stage IV resulted in the 

	greatest life expectancy. Surgery at stage IV was more effective 

	and more expensive than surgery at cancer diagnosis, with an incremental 

	cost of $3,200 per quality-adjusted life year gained. Surgery at 

	stage III was not a viable option. The results were robust to wide 

	variation in model parameters but were sensitive to the post-pancreaticoduodenectomy 

	quality of life score. CONCLUSIONS: Prophylactic pancreaticoduodenectomy 

	at stage IV duodenal polyposis in familial adenomatous polyposis 

	is a cost-effective approach that results in greater life expectancy 

	than surgery at either stage III or cancer diagnosis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Stout2009,

title = {Calibration methods used in cancer simulation models and suggested 

	reporting guidelines},

author = {N. K. Stout and Amy Knudsen and Chung Yin Kong and Pamela M. McMahon and G. Scott Gazelle},

url = {http://www.ncbi.nlm.nih.gov/pubmed/19663525},

year  = {2009},

date = {2009-01-01},

journal = {PharmacoEconomics},

volume = {27},

pages = {533-45},

abstract = {Increasingly, computer simulation models are used for economic and 

	policy evaluation in cancer prevention and control. A model's predictions 

	of key outcomes, such as screening effectiveness, depend on the values 

	of unobservable natural history parameters. Calibration is the process 

	of determining the values of unobservable parameters by constraining 

	model output to replicate observed data. Because there are many approaches 

	for model calibration and little consensus on best practices, we 

	surveyed the literature to catalogue the use and reporting of these 

	methods in cancer simulation models. We conducted a MEDLINE search 

	(1980 through 2006) for articles on cancer-screening models and supplemented 

	search results with articles from our personal reference databases. 

	For each article, two authors independently abstracted pre-determined 

	items using a standard form. Data items included cancer site, model 

	type, methods used for determination of unobservable parameter values 

	and description of any calibration protocol. All authors reached 

	consensus on items of disagreement. Reviews and non-cancer models 

	were excluded. Articles describing analytical models, which estimate 

	parameters with statistical approaches (e.g. maximum likelihood) 

	were catalogued separately. Models that included unobservable parameters 

	were analysed and classified by whether calibration methods were 

	reported and if so, the methods used. The review process yielded 

	154 articles that met our inclusion criteria and, of these, we concluded 

	that 131 may have used calibration methods to determine model parameters. 

	Although the term 'calibration' was not always used, descriptions of calibration or 'model fitting' were found in 50% (n = 66) of the articles, with an additional 16% (n = 21) providing a reference to 

	methods. Calibration target data were identified in nearly all of 

	these articles. Other methodological details, such as the goodness-of-fit metric, were discussed in 54% (n = 47 of 87) of the articles reporting 

	calibration methods, while few details were provided on the algorithms 

	used to search the parameter space. Our review shows that the use 

	of cancer simulation modelling is increasing, although thorough descriptions 

	of calibration procedures are rare in the published literature for 

	these models. Calibration is a key component of model development 

	and is central to the validity and credibility of subsequent analyses 

	and inferences drawn from model predictions. To aid peer-review and 

	facilitate discussion of modelling methods, we propose a standardized 

	Calibration Reporting Checklist for model documentation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Zauber2008,

title = {Evaluating test strategies for colorectal cancer screening: a decision analysis for the U.S. Preventive Services Task Force},

author = {A. G. Zauber and I. Lansdorp-Vogelaar and Amy Knudsen and J. Wilschut and M. Ballegooijen and K. M. Kuntz},

url = {http://www.ncbi.nlm.nih.gov/pubmed/18838717},

issn = {1539-3704 (Electronic) 0003-4819},

year  = {2008},

date = {2008-11-01},

urldate = {2008-11-01},

journal = {Ann Intern Med},

volume = {149},

number = {9},

pages = {659-69},

abstract = {BACKGROUND: The U.S. Preventive Services Task Force requested a decision 

	analysis to inform their update of recommendations for colorectal 

	cancer screening. OBJECTIVE: To assess life-years gained and colonoscopy 

	requirements for colorectal cancer screening strategies and identify 

	a set of recommendable screening strategies. DESIGN: Decision analysis 

	using 2 colorectal cancer microsimulation models from the Cancer 

	Intervention and Surveillance Modeling Network. DATA SOURCES: Derived 

	from the literature. TARGET POPULATION: U.S. average-risk 40-year-old 

	population. PERSPECTIVE: Societal. TIME HORIZON: Lifetime. INTERVENTIONS: 

	Fecal occult blood tests (FOBTs), flexible sigmoidoscopy, or colonoscopy 

	screening beginning at age 40, 50, or 60 years and stopping at age 

	75 or 85 years, with screening intervals of 1, 2, or 3 years for 

	FOBT and 5, 10, or 20 years for sigmoidoscopy and colonoscopy. Outcome 

	Measures: Number of life-years gained compared with no screening 

	and number of colonoscopies and noncolonoscopy tests required. RESULTS 

	OF BASE-CASE ANALYSIS: Beginning screening at age 50 years was consistently 

	better than at age 60. Decreasing the stop age from 85 to 75 years 

	decreased life-years gained by 1% to 4%, whereas colonoscopy use 

	decreased by 4% to 15%. Assuming equally high adherence, 4 strategies 

	provided similar life-years gained: colonoscopy every 10 years, annual 

	Hemoccult SENSA (Beckman Coulter, Fullerton, California) testing 

	or fecal immunochemical testing, and sigmoidoscopy every 5 years 

	with midinterval Hemoccult SENSA testing. Annual Hemoccult II and 

	flexible sigmoidoscopy every 5 years alone were less effective. RESULTS 

	OF SENSITIVITY ANALYSIS: The results were most sensitive to beginning 

	screening at age 40 years. Limitation: The stop age for screening 

	was based only on chronologic age. CONCLUSION: The findings support 

	colorectal cancer screening with the following: colonoscopy every 

	10 years, annual screening with a sensitive FOBT, or flexible sigmoidoscopy 

	every 5 years with a midinterval sensitive FOBT from age 50 to 75 

	years.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Pearson2008a,

title = {Assessing the comparative effectiveness of a diagnostic technology: CT colonography},

author = {Steven Pearson and Amy Knudsen and R. W. Scherer and J. Weissberg and G. Scott Gazelle},

url = {http://www.ncbi.nlm.nih.gov/pubmed/18997205},

issn = {1544-5208 (Electronic) 0278-2715},

year  = {2008},

date = {2008-00-01},

urldate = {2008-00-01},

journal = {Health Aff (Millwood)},

volume = {27},

number = {6},

pages = {1503-14},

abstract = {Medical imaging is a prime example of an innovation that has brought 

	important advances to medical care while triggering concerns about 

	potential overuse and excessive costs. Many hopes are riding on comparative 

	effectiveness research to help guide better decision making to improve 

	quality and value. But the dynamic nature of medical imaging poses 

	challenges for the traditional paradigms of evidentiary review and 

	analysis at the heart of comparative effectiveness. This paper discusses 

	these challenges and presents policy lessons for manufacturers, evidence 

	reviewers, and decisionmakers, illustrated by an assessment of a 

	prominent emerging imaging technique: computed tomography (CT) colonography.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Knudsen2007,

title = {Use of modeling to evaluate the cost-effectiveness of cancer screening programs},

author = {Amy Knudsen and Pamela M. McMahon and G. Scott Gazelle},

url = {http://www.ncbi.nlm.nih.gov/pubmed/17210941},

year  = {2007},

date = {2007-01-01},

urldate = {2007-01-01},

journal = {J Clin Oncol},

volume = {25},

pages = {203-8},

abstract = {Cost-effectiveness analysis (CEA) is an analytic tool that provides 

	a framework for comparing the health benefits and resource expenditures 

	associated with competing medical and public health interventions, 

	thereby allowing decision makers to identify interventions that yield 

	the greatest amount of health, given their resource constraints. 

	Models are important components of most, if not all, CEAs, and they 

	play a key role in evaluating the cost-effectiveness of cancer screening 

	programs, in particular. In this article, we describe the basic types 

	of models used to evaluate cancer screening programs and provide 

	examples of the use of models in CEAs and to guide cancer screening 

	policy. Finally, we offer some suggestions for important concepts 

	to consider when interpreting model results.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}