Inter‐test agreement and quantitative cross‐validation of immunochromatographical fecal occult blood tests

Abstract

Immunochromatographical fecal occult blood tests were shown to have higher sensitivity for detecting colorectal neoplasms than the commonly used guaiac-based test. However, positivity rates, sensitivity and specificity vary widely. We aimed to assess the reasons for this heterogeneity. Six dichotomous (qualitative) immunochromatographical tests were used in the same stool samples, taken before cathartic bowel preparation, from 1,330 participants of the German colonoscopy screening program. Positivity rates were determined, and inter-test agreement beyond chance was quantified by kappa coefficients (j). In addition, kappa coefficients were expressed in relation to their maximum possible values given differences in test positivity rates (j/j max ). Furthermore, the distribution of fecal hemoglobin concentration was assessed by an additional quantitative test in participants classified as clearly positive, borderline positive or clearly negative according to the qualitative tests. Positivity rates strongly varied from 6.4 to 46.8%. As a result, overall agreement between tests was only poor to moderate, with j ranging from 0.14 to 0.61. However, apart from the different positivity rates, agreement was mostly very high, with j/j max ranging from 0.53 to 1.00, and exceeding 0.70 in 12 of 15 cases. Distribution of fecal hemoglobin concentrations in the various categories strongly varied across tests. The observed patterns suggest that the strongly different positivity rates essentially reflect different cutoff levels of tests with otherwise very high inter-test agreement. Definition of cutoffs is a critical issue in the application of immunochromatographical tests and should be redefined for several of these tests.Fecal occult blood tests (FOBTs) are widely recommended and used for early detection of colorectal cancer (CRC) and its precursors.1 In particular, the guaiac-based FOBT, whose application has been shown to reduce incidence and mortality of CRC under trial conditions, 2 has been used for decades. In recent years, there has been increasing interest in immunochemical FOBTs, which overcome several analytical problems and might show better diagnostic performance compared with the guaiac-based FOBT.3-9 Both quantitative and qualitative (dichotomous) tests have been developed and are propagated for population-based screening. The latter are chromatographical tests requiring a visual interpretation of test results as positive or negative. A major advantage of immunochromatographical tests is their easy on-site implementation without the need of specific laboratory equipment. However, recent studies have disclosed major differences in the analytical performance of various tests. 7,10 In particular,we have shown in a study among 1,319 participants of screening colonoscopy that positivity rates, sensitivity and specificity of 6 qualitative immunochromatographical FOBTs, taken on stool samples from a single bowel movement, were varying widely across tests. 7 We aimed to explore the reasons for this heterogeneity by (i) ...

A future for faecal haemoglobin measurements in the medical laboratory

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“…The values range from 29 to 72% (ref. 13 ), owing to different sampling devices and different stabilities of the haemoglobin extract in the sampling buffer. Additional biochemical markers, such as haptoglobin and transferrin, are sometimes used as a second analyte detected in these test, in order to increase screening accuracy 14,15 .…”