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Abstract

Comparing a new diagnostic with available methods to gain some idea about its performance at the early stage of usage is necessary. When the new diagnostic has evidently better sensitivity than the reference, poor specificity will surely be incurred. A latent class analysis has been introduced to overcome this disadvantage1Agarwal R. Maskey D. Aggarwal A.N. et al.Diagnostic performance of various tests and criteria employed in allergic bronchopulmonary aspergillosis: a latent class analysis.PLoS One. 2013; 8e61105Crossref PubMed Scopus (114) Google Scholar; however, it had seldom been used for TB diagnostic evaluation. Complexity and the need for knowledge of mathematics or statistics might be the main reasons impeding its application. Because of the paucibacillary characteristic of some type of TB, a composite reference standard (CRS) is frequently used as the “gold standard” for new diagnostic evaluation.2Bahr N.C. Nuwagira E. Evans E.E. et al.Diagnostic accuracy of Xpert MTB/RIF Ultra for tuberculous meningitis in HIV-infected adults: a prospective cohort study.Lancet Infect Dis. 2018; 18: 68-75Abstract Full Text Full Text PDF PubMed Scopus (184) Google Scholar A CRS is composed of clinical, laboratory, histopathologic, and radiologic examination features, follow-up data, and so on, and it is like latent class analysis to some extent. In our previous study on the validation of Xpert Ultra for pleural TB diagnosis, we used a CRS as well.3Wang G. Wang S. Yang X. et al.Accuracy of Xpert MTB/RIF Ultra for the diagnosis of pleural TB in a multicenter cohort study.Chest. 2020; 157: 268-275Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar We integrated Xpert assay outcome into the CRS because of its routine usage in China. If we exclude the Xpert assay from the CRS, our confirmed case number decreases from 117 to 102, but the sensitivity of Xpert and Xpert Ultra remains similar to that in the previous study (34 of 102 [33.33%] and 66 of 102 [64.71%], respectively; 40 of 117 [34.19%] and 74 of 117 [63.25%], respectively, in our previous study). The 15 Xpert-positive but microbiologic examination-negative cases would then be categorized into the probable pleural TB group; but this change would not affect the total sensitivity and specificity of the study. Therefore, we presume that evaluation of a new TB diagnostic, using the composite reference standard, is valuable and feasible. Beside the CRS, we further analyzed the sensitivities of the diagnostics among all the patients with any bacterial evidence of TB, including the Xpert Ultra assay itself. We compared the performance of Xpert and Xpert Ultra in parallel to demonstrate the superiority of Xpert Ultra in sensitivity over Xpert. This strategy is often used in studies with very low positive case numbers,2Bahr N.C. Nuwagira E. Evans E.E. et al.Diagnostic accuracy of Xpert MTB/RIF Ultra for tuberculous meningitis in HIV-infected adults: a prospective cohort study.Lancet Infect Dis. 2018; 18: 68-75Abstract Full Text Full Text PDF PubMed Scopus (184) Google Scholar or specimens with a very low bacillus-positive rate.4Wang G. Wang S. Jiang G. et al.Xpert MTB/RIF Ultra improved the diagnosis of paucibacillary tuberculosis: a prospective cohort study.J Infect. 2019; 78: 311-316Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar This practice requires that the evaluated test have very high specificity, so that we can assume that the positive outcome of the new diagnostic may be trusted. This further analysis could improve the understanding of the new diagnostic, and could be used as a supplemental analysis. Accuracy of Xpert MTB/RIF Ultra for the Diagnosis of Pleural TB in a Multicenter Cohort StudyCHESTVol. 157Issue 2PreviewThe Xpert MTB/RIF (Xpert) assay has greatly improved the diagnosis of TB and identification of resistance to rifampicin (RIF). However, sensitivity of Xpert remains poor for pleural fluid detection. This study evaluated the performance of the novel next-generation Xpert MTB/RIF Ultra (Xpert Ultra) in comparison with Xpert for pleural TB diagnosis. Full-Text PDF Can a Test Being Evaluated in a Study Be Itself Used as a Reference Standard?CHESTVol. 159Issue 1PreviewWe read the article by Wang et al1 in CHEST (February 2020).1 We congratulate the authors for an interesting study. We do, however, have a specific question regarding the reference standard used in the study. Full-Text PDF