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Limburg, P. J.

Publications and source records attributed to Limburg, P. J..

2 recordsLinked to original sources
bioRxiv2020

Estimating the impact of differential adherence on the comparative effectiveness of stool-based colorectal cancer screening using the CRC-AIM microsimulation model

BackgroundReal-world adherence to colorectal cancer (CRC) screening strategies is imperfect. The CRC-AIM microsimulation model was used to estimate the impact of imperfect adherence on the relative benefits and burdens of guideline-endorsed, stool-based screening strategies. MethodsPredicted outcomes of multi-target stool DNA (mt-sDNA), fecal immunochemical tests (FIT), and high-sensitivity guaiac-based fecal occult blood tests (HSgFOBT) were simulated for 40-year-olds free of diagnosed CRC. For robustness, imperfect adherence was incorporated in multiple ways and with extensive sensitivity analysis. Analysis 1 assumed adherence from 0%-100%, in 10% increments. Analysis 2 longitudinally applied real-world first-round differential adherence rates (base-case imperfect rates=40% annual FIT vs 34% annual HSgFOBT vs 70% triennial mt-sDNA). Analysis 3 randomly assigned individuals to receive 1, 5, or 9 lifetime (9=100% adherence) mt-sDNA tests and 1, 5, or 9 to 26 (26=100% adherence) FIT tests. Outcomes are reported per 1000 individuals compared with no screening. ResultsEach screening strategy decreased CRC incidence and mortality versus no screening. In individuals screened between ages 50-75 and adherence ranging from 10%-100%, the life-years gained (LYG) for triennial mt-sDNA ranged from 133.1-300.0, for annual FIT from 96.3-318.1, and for annual HSgFOBT from 99.8-320.6. At base-case imperfect adherence rates, mt-sDNA resulted in 19.1% more LYG versus FIT, 25.4% more LYG versus HSgFOBT, and generally had preferable efficiency ratios while offering the most LYG. Completion of at least 21 FIT tests is needed to reach approximately the same LYG achieved with 9 mt-sDNA tests. ConclusionsAdherence assumptions affect the conclusions of CRC screening microsimulations that are used to inform CRC screening guidelines. LYG from FIT and HSgFOBT are more sensitive to changes in adherence assumptions than mt-sDNA because they require more tests be completed for equivalent benefit. At imperfect adherence rates, mt-sDNA provides more LYG than FIT or HSgFOBT at an acceptable tradeoff in screening burden.

cancer biology↗
bioRxiv2020

Description and Validation of the Colorectal Cancer and Adenoma Incidence & Mortality (CRC-AIM) Microsimulation Model

BackgroundMicrosimulation models of colorectal cancer (CRC) have helped inform national screening guidelines and health policy decision-making. However, detailed descriptions of particular underlying assumptions are not published, limiting access to robust platforms for exploratory analyses. We describe the development and validation of the Colorectal Cancer and Adenoma Incidence and Mortality (CRC-AIM) microsimulation model, a robust model built to facilitate collaborative simulation studies on disease progression and early detection through screening interventions. DesignWe used the Cancer Intervention and Surveillance Modeling Network (CISNET) CRC models, specifically CRC-SPIN, as a foundation for CRC-AIMs formulas and parameters. In addition, we developed novel submodels and recalibrated various parameters to address gaps and discrepancies in publicly available information. Along with evaluating the natural history and screening detection outcomes from CRC-AIM, we determined the impact of using different life tables (cohort versus period) on natural history outcomes. ResultsCRC-AIM demonstrated substantial cross-model validity when comparing multiple natural history and screening outputs and probability curves to those from CISNET models, particularly CRC-SPIN. Additionally, using period life tables, CRC-AIMs cumulative probability of developing CRC from ages 40 to 100 (7.1%) lies within the range of the CISNET models (6.7% to 7.2%). Using cohort tables, that probability increases to 8.0%. One notable difference is that, regardless of life table used, the cumulative probability of dying from CRC (3.2% for period; 3.8% for cohort) is slightly higher in CRC-AIM than the CISNET models (2.7% to 2.8%), due to CRC-AIMs different methodology for determining survival. Additionally, there is substantial overlap (e.g. 94-95% overall agreement for strategies on and off the efficient frontier for stool-based strategies) across multiple screening overlay outputs between CRC-AIM and the CISNET models, especially CRC-SPIN. ConclusionsWe developed and validated a robust CRC microsimulation model, CRC-AIM, and demonstrate the influence of life table choice on downstream outputs. We further describe CRC-AIMs parameters and include complete component tables to enhance transparency and encourage collaboration.

cancer biology↗