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Med Decis Making. 2016 Jul;36(5):604-14. doi: 10.1177/0272989X15622642. Epub 2016 Jan 8.

Validation of Models Used to Inform Colorectal Cancer Screening Guidelines: Accuracy and Implications.

Author information

RAND Corporation, Santa Monica, CA, USA (CMR)
Institute for Technology Assessment, Massachusetts General Hospital, Boston, MA, USA (ABK)
Department of Biostatistics, University of Washington, Seattle, WA, USA (TLM)
National Cancer Institute, Health Systems & 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 Health, Erasmus MC, Rotterdam, Netherlands (MVB, IL)
Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA (AGZ)



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.


colorectal cancer; discrete event simulation; gastroenterology; preventive medicine; simulation methods

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