Several studies have now examined the influence of the number of samples used for testing on clinical
sensitivity and specificity. Allison takes any positive result from 3 stool samples measured using
FlexSure OBT as an indication for referral and shows higher sensitivity for cancer than studies using single stool samples (Allison et al. 2007). Unsurprisingly other studies show agreement with that
conclusion (St John et al. 1993; Allison et al. 1996; Knaani & Samuel 1997; Nakama et al. 1999;
Greenberg et al. 2000; Nakama, Zhang & Fattah 2000; Rozen, Wong et al. 2003). Nakama et al. using
Monohaem, showed sensitivities of 89% for cancer with 3 stools compared with 56% for a single stool
(Nakama et al. 1999).
Using Hem-SP, Morikawa showed low sensitivity for cancer using a single-day sample (Morikawa et al.
2005). Rozen et al. (2006) used 3 stools for the OC-Sensor which contrasts with 2-day samples used
in Japan (Nakama, Zhang & Fattah 2000) and 1-day biennial testing performed in Italy (Castiglione et
al. 2002). The relative insensitivity in the Italian study to lesions in the proximal bowel (16.3 vs
30.7%) raises further doubts about the use of a single-day sample. In a study using OC-Sensor in an
at-risk population, Levi et al. (2007) took numeric measurements from three samples and used the
highest concentration of the three as the discriminating factor. Recent studies have taken the average
concentration from 2 stool measurements as the discriminating parameter, an approach that reduces
the positivity rate.
The use of different cut-off limits and different numbers of stool samples illustrates how programme
algorithms can manipulate clinical sensitivities and specificities for the lesions of interest. Chen
describes the use of a cost-effectiveness model as a method of determining the optimal cut-off
concentration for an iFOBT (Chen et al. 2007). In the study by Levi et al. (2007) using an iFOBT OCMicro,
a scatter plot of 2 consecutive samples showed that of those with cancer or adenomas, 21 of
91 had elevated or markedly elevated faecal blood in one sample but were normal in the other. This is
further evidence of intermittent or variable bleeding, sample heterogeneity or poor sample technique
that will reduce clinical sensitivity. Imperiale (2007) commenting on the paper by Levi in his editorial
in Annals of Internal Medicine (Levi et al. 2007), speculated that concentration-related clinical
sensitivity and specificity could be used to determine post-test risk. If risk was related to subject age
or sex, this would provide more sophisticated criteria for colonoscopy referral than is currently used.
