Dr. Knudsen, a Senior Scientist at the MGH Institute for Technology Assessment and an Assistant Professor at Harvard Medical School, has expertise in decision science. Her research focus is on development and application of data analytics and simulation models to address important questions pertaining to cancer prevention and opioid misuse reduction. Recognized nationally for her leadership in decision science and colorectal cancer screening, Dr. Knudsen's research has significantly influenced national colorectal cancer screening policies. This includes contributions to the Centers for Medicare and Medicaid Services’ National Coverage Determinations for colorectal cancer screening tests and the screening recommendations of both the US Preventive Services Task Force and the American Cancer Society.
Notably, Dr. Knudsen developed one of the three colorectal cancer models funded by the National Cancer Institute’s Cancer Intervention and Surveillance Modeling Network (CISNET), a consortium of independent research teams focused on evaluating cancer-control policies.
Dr. Knudsen received a BS with Distinction in policy analysis from Cornell University and a PhD in Health Policy from Harvard University. While at Harvard, Amy was the recipient of a Cancer Prevention Training Grant from the National Cancer Institute (NCI) and a Dissertation Completion Fellowship from Harvard University. She completed a NCI-funded post-doctoral fellowship in the Dana-Farber/Harvard Cancer Center Program in Cancer Outcomes Research Training (PCORT). She has worked for health-economics consulting firms where she developed decision-analytic models to assess the lifetime health and economic consequences of obesity and the benefits of weight loss.
Dr. Knudsen’s career goal is to improve cancer outcomes by identifying the most effective and cost-effective options for prevention, screening, and treatment. Her research focuses on the use of disease simulation models to inform cancer control policies. Her work to date has focused on colorectal cancer, the second most common cause of cancer death in the US. She developed and programmed a computer model, SimCRC, that simulates the natural history of colorectal cancer among the US population over time and incorporates the effects of prevention, screening, and treatment interventions. SimCRC has been used to inform both state- and national screening coverage decisions and guidelines. Dr. Knudsen’s research aims to evaluate how existing and emerging screening methodologies can best be used to minimize the burden of colorectal cancer.
Selected Publications
van den Puttelaar, Rosita; de Lima, Pedro Nascimento; Knudsen, Amy B; Rutter, Carolyn M; Kuntz, Karen M; de Jonge, Lucie; Escudero, Fernando Alarid; Lieberman, David; Zauber, Ann G; Hahn, Anne I; Inadomi, John M; Lansdorp-Vogelaar, Iris
In: Gastroenterology, vol. 167, no. 2, pp. 368–377, 2024, ISSN: 1528-0012.
@article{pmid38552671b,
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 = {2024-07-01},
journal = {Gastroenterology},
volume = {167},
number = {2},
pages = {368--377},
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.},
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pubstate = {published},
tppubtype = {article}
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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.
Pineda-Antunez, Carlos; Seguin, Claudia; van Duuren, Luuk A; Knudsen, Amy B; Davidi, Barak; de Lima, Pedro Nascimento; Rutter, Carolyn; Kuntz, Karen M; Lansdorp-Vogelaar, Iris; Collier, Nicholson; Ozik, Jonathan; Alarid-Escudero, Fernando
Emulator-Based Bayesian Calibration of the CISNET Colorectal Cancer Models Journal Article
In: Med Decis Making, vol. 44, no. 5, pp. 543-553, 2024, ISSN: 1552-681X.
@article{pmid38858832,
title = {Emulator-Based Bayesian Calibration of the CISNET Colorectal Cancer Models},
author = {Carlos Pineda-Antunez and Claudia Seguin and Luuk A van Duuren and Amy B Knudsen and Barak Davidi and Pedro Nascimento de Lima and Carolyn Rutter and Karen M Kuntz and Iris Lansdorp-Vogelaar and Nicholson Collier and Jonathan Ozik and Fernando Alarid-Escudero},
doi = {10.1177/0272989X241255618},
issn = {1552-681X},
year = {2024},
date = {2024-07-01},
urldate = {2024-07-01},
journal = {Med Decis Making},
volume = {44},
number = {5},
pages = {543-553},
abstract = {PURPOSE: To calibrate Cancer Intervention and Surveillance Modeling Network (CISNET)\'s SimCRC, MISCAN-Colon, and CRC-SPIN simulation models of the natural history colorectal cancer (CRC) with an emulator-based Bayesian algorithm and internally validate the model-predicted outcomes to calibration targets.nnMETHODS: We used Latin hypercube sampling to sample up to 50,000 parameter sets for each CISNET-CRC model and generated the corresponding outputs. We trained multilayer perceptron artificial neural networks (ANNs) as emulators using the input and output samples for each CISNET-CRC model. We selected ANN structures with corresponding hyperparameters (i.e., number of hidden layers, nodes, activation functions, epochs, and optimizer) that minimize the predicted mean square error on the validation sample. We implemented the ANN emulators in a probabilistic programming language and calibrated the input parameters with Hamiltonian Monte Carlo-based algorithms to obtain the joint posterior distributions of the CISNET-CRC models\' parameters. We internally validated each calibrated emulator by comparing the model-predicted posterior outputs against the calibration targets.nnRESULTS: The optimal ANN for SimCRC had 4 hidden layers and 360 hidden nodes, MISCAN-Colon had 4 hidden layers and 114 hidden nodes, and CRC-SPIN had 1 hidden layer and 140 hidden nodes. The total time for training and calibrating the emulators was 7.3, 4.0, and 0.66 h for SimCRC, MISCAN-Colon, and CRC-SPIN, respectively. The mean of the model-predicted outputs fell within the 95% confidence intervals of the calibration targets in 98 of 110 for SimCRC, 65 of 93 for MISCAN, and 31 of 41 targets for CRC-SPIN.nnCONCLUSIONS: Using ANN emulators is a practical solution to reduce the computational burden and complexity for Bayesian calibration of individual-level simulation models used for policy analysis, such as the CISNET CRC models. In this work, we present a step-by-step guide to constructing emulators for calibrating 3 realistic CRC individual-level models using a Bayesian approach.nnHIGHLIGHTS: We use artificial neural networks (ANNs) to build emulators that surrogate complex individual-based models to reduce the computational burden in the Bayesian calibration process.ANNs showed good performance in emulating the CISNET-CRC microsimulation models, despite having many input parameters and outputs.Using ANN emulators is a practical solution to reduce the computational burden and complexity for Bayesian calibration of individual-level simulation models used for policy analysis.This work aims to support health decision scientists who want to quantify the uncertainty of calibrated parameters of computationally intensive simulation models under a Bayesian framework.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
PURPOSE: To calibrate Cancer Intervention and Surveillance Modeling Network (CISNET)'s SimCRC, MISCAN-Colon, and CRC-SPIN simulation models of the natural history colorectal cancer (CRC) with an emulator-based Bayesian algorithm and internally validate the model-predicted outcomes to calibration targets.nnMETHODS: We used Latin hypercube sampling to sample up to 50,000 parameter sets for each CISNET-CRC model and generated the corresponding outputs. We trained multilayer perceptron artificial neural networks (ANNs) as emulators using the input and output samples for each CISNET-CRC model. We selected ANN structures with corresponding hyperparameters (i.e., number of hidden layers, nodes, activation functions, epochs, and optimizer) that minimize the predicted mean square error on the validation sample. We implemented the ANN emulators in a probabilistic programming language and calibrated the input parameters with Hamiltonian Monte Carlo-based algorithms to obtain the joint posterior distributions of the CISNET-CRC models' parameters. We internally validated each calibrated emulator by comparing the model-predicted posterior outputs against the calibration targets.nnRESULTS: The optimal ANN for SimCRC had 4 hidden layers and 360 hidden nodes, MISCAN-Colon had 4 hidden layers and 114 hidden nodes, and CRC-SPIN had 1 hidden layer and 140 hidden nodes. The total time for training and calibrating the emulators was 7.3, 4.0, and 0.66 h for SimCRC, MISCAN-Colon, and CRC-SPIN, respectively. The mean of the model-predicted outputs fell within the 95% confidence intervals of the calibration targets in 98 of 110 for SimCRC, 65 of 93 for MISCAN, and 31 of 41 targets for CRC-SPIN.nnCONCLUSIONS: Using ANN emulators is a practical solution to reduce the computational burden and complexity for Bayesian calibration of individual-level simulation models used for policy analysis, such as the CISNET CRC models. In this work, we present a step-by-step guide to constructing emulators for calibrating 3 realistic CRC individual-level models using a Bayesian approach.nnHIGHLIGHTS: We use artificial neural networks (ANNs) to build emulators that surrogate complex individual-based models to reduce the computational burden in the Bayesian calibration process.ANNs showed good performance in emulating the CISNET-CRC microsimulation models, despite having many input parameters and outputs.Using ANN emulators is a practical solution to reduce the computational burden and complexity for Bayesian calibration of individual-level simulation models used for policy analysis.This work aims to support health decision scientists who want to quantify the uncertainty of calibrated parameters of computationally intensive simulation models under a Bayesian framework.
Lima, Pedro Nascimento De; Puttelaar, Rosita Van Den; Knudsen, Amy B; Hahn, Anne I; Kuntz, Karen M; Ozik, Jonathan; Collier, Nicholson; Alarid-Escudero, Fernando; Zauber, Ann G; Inadomi, John M; Lansdorp-Vogelaar, Iris; Rutter, Carolyn M
Characteristics of a cost-effective blood test for colorectal cancer screening Journal Article
In: J Natl Cancer Inst, 2024, ISSN: 1460-2105.
@article{pmid38845072,
title = {Characteristics of a cost-effective blood test for colorectal cancer screening},
author = {Pedro Nascimento De Lima and Rosita Van Den Puttelaar and Amy B Knudsen and Anne I Hahn and Karen M Kuntz and Jonathan Ozik and Nicholson Collier and Fernando Alarid-Escudero and Ann G Zauber and John M Inadomi and Iris Lansdorp-Vogelaar and Carolyn M Rutter},
doi = {10.1093/jnci/djae124},
issn = {1460-2105},
year = {2024},
date = {2024-06-01},
journal = {J Natl Cancer Inst},
abstract = {BACKGROUND: Blood-based biomarker tests can potentially change the landscape of colorectal cancer (CRC) screening. We characterize the conditions under which blood test screening would be as effective and cost-effective as annual fecal immunochemical testing (FIT) or decennial colonoscopy.nnMETHODS: We used the three CISNET-Colon models to compare scenarios of no screening, annual FIT, decennial colonoscopy, and a blood test meeting CMS coverage criteria (74% CRC sensitivity and 90% specificity). We varied the sensitivity to detect CRC (74%-92%), advanced adenomas (AAs, 10%-50%), screening interval (1-3 years), and test cost ($25-$500). Primary outcomes included quality-adjusted life-years gained (QALYG) from screening and costs for an US average-risk 45-year-old cohort.nnRESULTS: Annual FIT yielded 125-163 QALYG per 1,000 at a cost of $3,811-5,384 per person, whereas colonoscopy yielded 132-177 QALYG at a cost of $5,375-7,031 per person. A blood test with 92% CRC sensitivity and 50% AA sensitivity yielded 117-162 QALYG if used every three years and 133-173 QALYG if used every year but would not be cost-effective if priced above $125 per test. If used every three years, a $500 blood test only meeting CMS coverage criteria yielded 83-116 QALYG, at a cost of $8,559-9,413 per person.nnCONCLUSION: Blood tests that only meet CMS coverage requirements should not be recommended to patients who would otherwise undergo screening by colonoscopy or FIT due to lower benefit. Blood tests need higher AA sensitivity (above 40%) and lower costs (below $125) to be cost-effective.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Blood-based biomarker tests can potentially change the landscape of colorectal cancer (CRC) screening. We characterize the conditions under which blood test screening would be as effective and cost-effective as annual fecal immunochemical testing (FIT) or decennial colonoscopy.nnMETHODS: We used the three CISNET-Colon models to compare scenarios of no screening, annual FIT, decennial colonoscopy, and a blood test meeting CMS coverage criteria (74% CRC sensitivity and 90% specificity). We varied the sensitivity to detect CRC (74%-92%), advanced adenomas (AAs, 10%-50%), screening interval (1-3 years), and test cost ($25-$500). Primary outcomes included quality-adjusted life-years gained (QALYG) from screening and costs for an US average-risk 45-year-old cohort.nnRESULTS: Annual FIT yielded 125-163 QALYG per 1,000 at a cost of $3,811-5,384 per person, whereas colonoscopy yielded 132-177 QALYG at a cost of $5,375-7,031 per person. A blood test with 92% CRC sensitivity and 50% AA sensitivity yielded 117-162 QALYG if used every three years and 133-173 QALYG if used every year but would not be cost-effective if priced above $125 per test. If used every three years, a $500 blood test only meeting CMS coverage criteria yielded 83-116 QALYG, at a cost of $8,559-9,413 per person.nnCONCLUSION: Blood tests that only meet CMS coverage requirements should not be recommended to patients who would otherwise undergo screening by colonoscopy or FIT due to lower benefit. Blood tests need higher AA sensitivity (above 40%) and lower costs (below $125) to be cost-effective.
van den Puttelaar, Rosita; de Lima, Pedro Nascimento; Knudsen, Amy B; Rutter, Carolyn M; Kuntz, Karen M; de Jonge, Lucie; Escudero, Fernando Alarid; Lieberman, David; Zauber, Ann G; Hahn, Anne I; Inadomi, John M; Lansdorp-Vogelaar, Iris
In: Gastroenterology, 2024, ISSN: 1528-0012.
@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}
}
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.
Peters, Mary Linton B; Eckel, Andrew; Seguin, Claudia L; Davidi, Barak; Howard, David H; Knudsen, Amy B; Pandharipande, Pari V
Cost-Effectiveness Analysis of Screening for Pancreatic Cancer Among High-Risk Populations Journal Article
In: JCO Oncol Pract, vol. 20, iss. 2, pp. 278-290, 2024, ISSN: 2688-1535.
@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 = {},
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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.
Knudsen, Amy B; Trentham-Dietz, Amy; Kim, Jane J; Mandelblatt, Jeanne S; Meza, Rafael; Zauber, Ann G; Castle, Philip E; Feuer, Eric J
Estimated US Cancer Deaths Prevented With Increased Use of Lung, Colorectal, Breast, and Cervical Cancer Screening Journal Article
In: JAMA Netw Open, vol. 6, no. 11, pp. e2344698, 2023, ISSN: 2574-3805.
@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.},
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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.
van den Berg, Danica M N; de Lima, Pedro Nascimento; Knudsen, Amy B; Rutter, Carolyn M; Weinberg, David; and, Iris Lansdorp-Vogelaar
NordICC Trial Results in Line With Expected Colorectal Cancer Mortality Reduction After Colonoscopy: A Modeling Study Journal Article
In: Gastroenterology, vol. 165, no. 4, pp. 1077–1079.e2, 2023, ISSN: 1528-0012.
@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}
}
Seguin, Claudia L; Davidi, Barak; Peters, Mary Linton B; Eckel, Andrew; Harisinghani, Mukesh G; Goiffon, Reece J; Knudsen, Amy B; Pandharipande, Pari V
Ultrasound Surveillance of Small, Incidentally Detected Gallbladder Polyps: Projected Benefits by Sex, Age, and Comorbidity Level Journal Article
In: J Am Coll Radiol, vol. 20, no. 10, pp. 1031-1041, 2023, ISSN: 1558-349X.
@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}
}
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.
van den Berg, Danica M N; de Lima, Pedro Nascimento; Knudsen, Amy B; Rutter, Carolyn M; Weinberg, David; and, Iris Lansdorp-Vogelaar
NordICC trial results in line with expected colorectal cancer mortality reduction after colonoscopy: a modelling study Journal Article
In: Gastroenterology, 2023, ISSN: 1528-0012.
@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}
}
Zauber, Ann G; Winawer, Sidney J; O'Brien, Michael J; Mills, Glenn M; Allen, John I; Feld, Andrew D; Jordan, Paul A; Fleisher, Martin; Orlow, Irene; Meester, Reinier G S; Lansdorp-Vogelaar, Iris; Rutter, Carolyn M; Knudsen, Amy B; Mandelson, Margaret; Shaukat, Aasma; Mendelsohn, Robin B; Hahn, Anne I; Lobaugh, Stephanie M; Palmer, Brittany Soto; Serrano, Victoria; Kumar, Julie R; Fischer, Sara E; Chen, Jennifer C; Bayuga-Miller, Sharon; Kuk, Deborah; O'Connell, Kelli; Church, Timothy R
Randomized Trial of Facilitated Adherence to Screening Colonoscopy vs Sequential Fecal-Based Blood Test Journal Article
In: Gastroenterology, vol. 165, iss. 1, pp. 252-266, 2023, ISSN: 1528-0012.
@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}
}
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.