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

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.