Appendix 1b: Description of the SimCRC model for natural history and intervention model
SimCRC Model
SimCRC overview. The SimCRC model of CRC was developed to evaluate the impact of past and future interventions on CRC incidence and mortality in the U.S. The model is population-based, meaning that it simulates the life histories of multiple cohorts of individuals of a given year of birth. These cohorts can be aggregated to yield a full cross-section of the population in a given calendar year. For this analysis, we simulated the life histories of only one cohort—those aged 65 years in 2005. SimCRC is a hybrid model, specifically it is a cross between a Markov model and a discrete event simulation. While annual (often age-specific) probabilities define the likelihood of transitioning through a series of health states, the model does not have annual cycles. Instead, the age at which a given transition takes place for each simulated individual is drawn from a cumulative probability function.
SimCRC simulation of the natural history of CRC. The SimCRC natural history model describes the progression of underlying colorectal disease (i.e., the adenoma-carcinoma sequence) among an unscreened population. Each simulated individual is assumed to be free of adenomas and CRC at birth. Over time, he is at risk of forming one or more adenomas. Each adenoma may grow in size from small (≤5 mm) to medium (6-9 mm) to large (≥10 mm). Medium and large adenomas may progress to preclinical CRC, although most will not in an individual's lifetime. Preclinical cancers may progress in stage (I-IV) and may be detected via symptoms, becoming a clinical case. Individuals with CRC may die from their cancer or from other causes.
The SimCRC model allows for heterogeneity in growth and progression rates across multiple adenomas within an individual. While all adenomas have the potential to develop into CRC, most will not. The likelihood of adenoma growth and progression to CRC is allowed to vary by location in the colorectal tract (i.e., proximal colon vs. distal colon vs. rectum).
SimCRC simulation of screening. The screening component of the SimCRC model is superimposed on the natural history model. It allows for the detection and removal of adenomas and the diagnosis of preclinical CRC. In a screening year, a person with an underlying (i.e., undiagnosed) adenoma or preclinical cancer faces the chance that the lesion is detected based on the sensitivity of the test for adenomas by size or for cancer and the reach of the test. Individuals who do not have an underlying adenoma or preclinical cancer also face the risk of having a positive screening test (and undergoing unnecessary follow-up procedures) due to the imperfect specificity of the test. While the model does not explicitly simulate non-adenomatous polyps, they are accounted for through the specificity of the test. Additionally, individuals with false-negative screening tests (i.e., individuals with an adenoma or preclinical cancer that was missed by the screening test) may be referred for follow-up due to the detection of non-adenomatous polyps. The model incorporates the risk of fatal and non-fatal complications associated with various screening procedures. It also accounts for the fact that not all individuals are adherent with CRC screening guidelines and that adherence patterns are correlated within an individual.