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taken from the same area. Unfortunately, the authors do not report whether the samples were obtained from the same area, and if so, how the procedure was done. The k concordance coefficient between TBLC and the final diagnosis at the second multidisciplinary assessment (MDA2, or after biopsy) was 0.31 (95% confidence interval, 0.06–0.56), and that between SLB and the final diagnosis was 0.51 (95% confidence interval, 0.27–0.75). Sample-size calculation is required for studies that apply inferential statistics, and should be included in all protocols according to Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines, as failing to do so can lead to erroneous conclusions. Although the k coefficient does not have a defined sample-size calculation (as there is no standard null hypothesis value) and is highly dependent on the prespecified minimum acceptable level of agreement (not provided in this paper), as a general rule, sample sizes should not consist of fewer than 30 comparisons. One would expect conclusions drawn from only 17 cases to have little statistical value. Additionally, the results reported in this study are very difficult to interpret because the data were not blinded for the members of the MDA2. This means that three of the most influential biases that can affect the internal validity of any diagnostic accuracy study are present: clinical review bias (experimental tests are interpreted with knowledge of the participants’ clinical characteristics), test review bias (experimental tests are interpreted with knowledge of the reference standard test results), and diagnostic review bias (the reference standard test results are interpreted with knowledge of the experimental test results). Romagnoli and colleagues’ study makes an interesting contribution to the discussion about TBLC versus SLB. It will be difficult to conduct larger, statistically reliable series due to safety and ethical concerns. In view of the enormous potential of TBLC, however, it is important to address issues regarding diagnostic yield and safety in multicenter, randomized controlled trials. n

american journal of respiratory and critical care medicine

Cryobiopsy Compared with Surgical Lung Biopsy in ILD: Reply to Maldonado et al., Froidure et al., Bendstrup et al., Agarwal et al., Richeldi et al., Rajchgot et al., and Quadrelli et al.