Clinical performance

Description of terms used to describe test effectiveness 

gFOBT screening has been proven to be effective in reducing colorectal cancer mortality (Hewitson et al. 2007). In randomised trials the reduction in cause-specific mortality ranged from 15% (Hardcastle et al. 1996) to 33% (Mandel et al. 1993). Such a large variance in mortality can be explained by test differences, different numbers of faecal samples, different intervals between invitation cycles (one-year or two-year) and different responses to invitation associated with the characteristics and composition of the population screened. The sensitivity and specificity quoted for a test will therefore be influenced both by the test’s analytical characteristics and the context in which the test is used and evaluated.

gFOBTs come in two forms, the conventional form with normal sensitivity and the more sensitive variety, Hemoccult SENSA, in which the sample is hydrated before analysis. Hemoccult SENSA performs quite differently from the gFOBTs used in European trials (Hardcastle et al. 1996; Kronborg et al. 1996) and is both more sensitive and less specific. Comparison of the clinical performance of gFOBT and iFOBT is complex because iFOBTs can have different levels of specificity and sensitivity indeed they may have variable positive cut-off concentrations. Changes in cut-off concentrations result in different clinical performance characteristics.

Although only one population-based RCT has been described with iFOBT (van Rossum et al. 2008), the many published diagnostic accuracy studies provide information on the comparative ability of current tests to distinguish subjects with or without colorectal cancer and adenoma and can be considered an acceptable indication of the satisfactory performance of iFOBT in population screening (Burch et al. 2007). 

Diagnostic accuracy studies have compared: 

a) subjects performing one or both tests (gFOBT and iFOBT) and performing a total colonoscopy (or sigmoidoscopy) independently from the result of the test (cohort studies);

 b) subjects performing one or both tests and undergoing colonoscopy if one or both tests are positive (cohort studies); 

c) Diagnosis determined beforehand and the test performed subsequently (case-control studies); and 

d) Different subjects performing different tests 

Colorectal cancer, large adenomas ( 10 mm), high-risk adenomas (high-grade dysplasia, villous change, serrated histology or 3 polyps), all adenomas (including small adenomas), alone or combined have been used as reference standards in the various studies.

The comparative clinical performance of the different tests has usually been based on the following indicators: Sensitivity, specificity, Positive Predictive Value (PPV), false positive rate, likelihood ratio for a positive or a negative test which is derived from sensitivity and specificity (sensitivity/(1-specificity)) for + LR; (1-sensitivity)/specificity for –LR.