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Misclassification of patients by an imperfect reference test will lead to bias in the assessment of a diagnostic test [ 63, 64].
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In a first step, we assessed the bias of comparative measures of the diagnostic accuracy of two tests induced by the use of an imperfect reference test.
A CRS addresses an imperfect reference standard by adding a second test [ 13].
Potential explanations for this include SWE technology variation, type II error owing to small sample sizes, incorrect estimation of fibrosis by biopsy, which is known to be an imperfect reference standard, [ 34] operator variability, or a true lack of correlation.
CSF Gram staining and real-time PCR are theoretically less affected by antibiotics; however, it is difficult to evaluate these tests with an imperfect reference standard.
The Alere™ i test and real-time PCR diagnostic techniques were compared by PPA and NPA, considering the real-time PCR test as an imperfect reference standard.
Furthermore, arthroscopy also has limitations and should be considered an imperfect reference standard for grading of cartilage defects [27].
Finally, the comparison of a test against an imperfect reference standard could result in underestimation of test accuracy.
The true accuracy of commercial NAATs may actually be higher than reported when using an imperfect reference standard [140].
This could potentially result in an imperfect reference standard [ 35].
In general, an imperfect reference test will underestimate the performance of a diagnostic test.
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Justyna Jupowicz-Kozak
CEO of Professional Science Editing for Scientists @ prosciediting.com