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

PLoS One. 2020 Dec 29;15(12):e0244431. doi: 10.1371/journal.pone.0244431. eCollection 2020.


Background: Real-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.

Methods: Predicted 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.

Results: Each screening strategy decreased CRC incidence and mortality versus no screening. In individuals screened between ages 50-75 and adherence ranging from 10%a-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.

Conclusions: Adherence 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / epidemiology*
  • Colorectal Neoplasms / genetics
  • DNA / analysis*
  • Early Detection of Cancer / methods*
  • Female
  • Guideline Adherence
  • Humans
  • Incidence
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Models, Theoretical
  • Mortality
  • Occult Blood
  • Practice Guidelines as Topic


  • DNA

Grants and funding

Financial support for this study was provided by a contract with Exact Sciences Corporation. AP received compensation from Exact Sciences through a consulting agreement with Exact Sciences and EmpiriQA, LLC. LS, MM, ABO, and MP are employees of the study sponsor and received a salary. PJL is Chief Medical Officer for Screening at Exact Sciences but is not an employee of Exact Sciences. The specific roles of these authors are articulated in the ‘author contributions’ section. The funder had no other role in in study design, data collection and analysis, decision to publish, or preparation of the manuscript.