FIT as a Comparator for Evaluating the Effectiveness of New Non-invasive CRC Screening Test.

Randomized Controlled Trials (RCT) demonstrated that guaiac-based fecal occult blood test (gFOBT), sigmoidoscopy, or colonoscopy are effective at reducing colorectal cancer (CRC) risk and mortality. Even if the impact of fecal immunochemical test (FIT) has not been evaluated within population-based RCT with mortality as the outcome, the results of comparative analyses with gFOBT provide strong indirect evidence of its effectiveness. Extensive information is also available on sensitivity and specificity of FIT, compared with gFOBT. FIT has almost universally replaced gFOBT in organized screening programs worldwide. Using FIT as a comparator is an efficient way to evaluate the effectiveness of new tests, with respect to test performance and relevant intermediate outcomes such as rates of interval cancer and late-stage cancer incidence. Direct comparison with FIT in the pre-screening evaluation of the accuracy of the new test will guide selection of the cut-off of the new test, and document the potential gain in sensitivity. Comparison in cross-sectional single-round screening evaluation can either use paired or parallel designs. Only parallel designs allow direct comparisons of participation rates. Relative accuracy can be derived in both designs with an assumption of similar colorectal cancer and precursor prevalence between groups in parallel designs. Finally, multiple-rounds prospective comparison will document potential effect on risk of CRC and precancerous lesions, and on absolute reductions in late-stage incidence as a proxy of mortality. This paper provides an overview of evidence and rationale for using FIT as a comparator for evaluating new non-invasive tests with repeated testing at short intervals.