Colorectal Cancer Comparative Analyses

Cost Effectiveness of Stool DNA Screening for Colorectal Cancer

Stool DNA testing for the screening of colorectal cancer represents one of the new screening approaches which has been considered by the Centers for Medicare & Medicaid Services, often the first adopter of innovative screening tests.  CISNET modelers utilizing two different models analyzed the current conditions for which stool DNA could be cost-effective compared to current, reimbursable screening tests.  At the current estimated cost and a screening interval of every 3 5 years, modelers found stool DNA tests yielded fewer life-years and higher costs than established, recommended screening methods in both a cohort of CMS persons as well as those of average screening age, 50 years and older.  (Lansdorp-Vogelaar 2010).  Until overall cost of stool DNA screening decreases, this screening strategy does not represent a cost-effective alternative to the majority of currently reimbursable screening tests.

Using Microsimulation modeling to Inform Health Policy: Estimation of benefits, burden, and harms of CRC screening strategies for the US Preventive Services Task Force

The US Preventive Services Task Force requested a decision analysis from the CISNET colorectal working group to inform their updated recommendation process for CRC screening. This is the second time CISNET work has been used in the USPSTF recommendation process, and it was evaluated alongside a systematic review of clinical evidence. The CISNET team modeled 204 unique screening strategies, including ages to begin and end screening, screening intervals, and screening modality. CISNET models found that for screening between ages 50 and 75, there were four model-recommendable strategies: colonoscopy every 10 years, annual FIT, sigmoidoscopy every 5 years combined with annual FIT, and CT-colonography every 5 years. The supporting modeling paper points out the need for further clinical evidence on an earlier start age for CRC screening and test-specific adherence over multiple rounds of screening. Overall, however, while the models differed slightly in terms of absolute outcomes, they yielded consistent relative predictions across screening modalities and similar rankings within the different classes of modalities. This lends strength to the argument that model results are a valid source of data for informing health policy (Knudsen 2016). An interactive web resource for this paper can be found at:

Model Validation: accuracy of model predictions based on randomized trial data and implications for use

Models require assumptions about unobservable processes; in the case of CRC, this includes inputs of the natural history of disease. Because of these assumptions, it is important to assess a model's predictive accuracy based on clinical trial data. The CISNET group decided to validate all three CRC models against outcomes from the United Kingdom Flexible Sigmoidoscopy Screening (UKFSS) Trial, which was a randomized trial examining one-time flexible sigmoidoscopy. In this validation exercise, all three models accurately predicted the relative reduction in CRC mortality 10 years after screening. 10-year CRC incidence was accurately predicted in the two models with longer average preclinical duration. The MISCAN model underestimated the incidence reduction due to shorter dwell time estimates, and has since been recalibrated to yield predictions that are consistent with both mortality and incidence reductions. This exercise proved that model accuracy can be established only through external validation, and that such exercises are essential for the accuracy of any decision model (Rutter 2016).

Modeling Benefits and Harms of Screening Cessation Ages Based on Comorbid Conditions

The US Preventive Services Task Force has recommended against screening past the age of 74 for breast and colorectal cancers. However, as life expectancy increases and people are living longer, this may no longer be an effective screening stop age for everyone. In order to determine whether we could risk stratify screening cessation age, we modeled the benefits and harms of screening based on comorbid conditions. This comparative analysis was unique in that we modeled for three CISNET cancer sites: CRC, breast, and prostate. We found that comorbid conditions are an important determinant of both benefits and harms of screening. For persons with no, mild, moderate, and severe comorbid conditions, screening until ages 76, 74, 72, and 66 years, respectively, resulted in harms and benefits similar to average-health persons. These findings may help tailor personalized screening regimens for persons with differential comorbid conditions who want to continue screening past the recommended stop age of 74. (Lansdorp-Vogelaar 2014).