Comparison of a brush-sampling fecal immunochemical test for hemoglobin with a sensitive guaiac-based fecal occult blood test in detection of colorectal neoplasia

Authors

  • Robert H. Fletcher MD, MSc,

    1. Department of Ambulatory Care and Prevention, Harvard Medical School Cambridge, Massachusetts
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    • From 1998 to 2002, David Ransohoff was chair of the Scientific Advisory Board of Exact Sciences. Thomas Imperiale is a consultant for Exact Sciences. Robert Fletcher is a member of the Scientific Advisory Board of Exact Sciences, which has developed a DNA-based stool test for colorectal cancer.

  • David F. Ransohoff MD,

    1. Division of Gastroenterology, Department of Medicine, University of North Carolina Chapel Hill, North Carolina
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    • From 1998 to 2002, David Ransohoff was chair of the Scientific Advisory Board of Exact Sciences. Thomas Imperiale is a consultant for Exact Sciences. Robert Fletcher is a member of the Scientific Advisory Board of Exact Sciences, which has developed a DNA-based stool test for colorectal cancer.

  • Thomas F. Imperiale MD

    1. Division of Gastroenterology, Department of Medicine, Indiana University School of Medicine Indianapolis, Indiana
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    • From 1998 to 2002, David Ransohoff was chair of the Scientific Advisory Board of Exact Sciences. Thomas Imperiale is a consultant for Exact Sciences. Robert Fletcher is a member of the Scientific Advisory Board of Exact Sciences, which has developed a DNA-based stool test for colorectal cancer.


Smith et al.1 compared the performance of a fecal immunochemical test (FIT) for hemoglobin to a sensitive, guaiac-based fecal occult blood test (GFOBT) in a large cohort of average-risk adults and found that the FIT was more sensitive for cancers and significant adenomas. They report that “…the FIT returned a true-positive result…in cancer…[of] 87.5%.” Readers should not mistake this result for the true sensitivity in the usual sense: the proportion of all patients with cancer who have a positive test.

The study by Smith et al was conducted in such a way that true sensitivity is necessarily overestimated and easily can approach 100%. Almost all participants in this study underwent colonoscopy only if 1 of the 2 fecal occult blood tests was positive. Patients with cancer who had negative tests—which would have been counted as false-negative results, causing lower sensitivity—systematically were excluded. This problem, known as diagnostic work-up bias,2 would have been avoided only by performing colonoscopy on all members of the cohort, regardless of the test results.3

The extent to which the reported “true-positive rate” may have overestimated true sensitivity is illustrated by the following example: The literature suggests that no more than half of colorectal cancers bleed at a given point in time. If so, then at least 48 of the 2512 study participants would have had cancer, not just the 24 that were diagnosed because they bled, causing 1 or both of the tests to be positive. The true sensitivity for FIT then would have been 21 of 48 (43.8%), and not the 21 of 24 (87.5%) reported. Taking into account statistical uncertainty (the 95% confidence interval), sensitivity would have been in the 29% to 58% range. The “true positive rate” used for comparing 2 tests within a study like the one by Smith et al1 is not a valid estimate of true sensitivity for comparison with the sensitivities of other tests reported in the literature.

Robert H. Fletcher MD, MSc*, David F. Ransohoff MD†, Thomas F. Imperiale MD‡, * Department of Ambulatory Care and Prevention, Harvard Medical School Cambridge, Massachusetts, † Division of Gastroenterology, Department of Medicine, University of North Carolina Chapel Hill, North Carolina, ‡ Division of Gastroenterology, Department of Medicine, Indiana University School of Medicine Indianapolis, Indiana.

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