Subsequently, for the remaining 6 years of Rodin, there was a specified data collection form so that the trial was clearly prospective and involved both generation rFVIII concentrates. This article appears to have combined the data from both study periods in their biostatistical analysis rather than analysing the results separately as well as combined. It is not clear DAPT how this approach may have confounded their conclusions; however, there are currently in process several well-designed prospective studies, which may confirm or contradict Rodin’s findings. Two initial aspects of the Rodin trial design

should be examined. First, patients were allocated to the products indicated by their treaters and thus were subject to the potential ‘biases’ of their treaters and/or their Hemophilia Treatment Centers’ own local guidelines, preferences, or attitudes. It is indeed possible that such treatment decisions resulted in ascertainment or selection bias. Second, although the study authors discount the possibility that centre-specific bias could have confounded their conclusions,

given that the variability of prophylaxis Pictilisib regimens and intensity of treatment have already been adjusted for, it would have been more supportive and reassuring if alternative analytical approaches for this study design had been employed to control for the risk of bias. Such statistical techniques could have included propensity score analysis [8] and centre-stratified or adjusted Cox-regression, or an assessment of deviation from the overall mean rate of inhibitor formation in different centres. In the setting of a post hoc analysis, exploring 上海皓元 the potential sources of variability with multiple techniques is generally useful to distinguish robust findings from chance ones. A further methodological concern of the Rodin trial is that it relied on the Bethesda unit inhibitor levels to be measured at each individual HTC rather than performed at a central laboratory. It is not apparent whether all the HTC laboratories were standardized in their assay techniques. At first

reading this might appear irrelevant for the study, which focuses on only clinically relevant inhibitors, but this is not the case, because Rodin employed a highly laboratory-dependent definition of inhibitor clinical relevance. Of most concern in the Rodin study design is the possible deviation from the complete analysis of the entire inception cohort [9]. According to the Methods of the Rodin study, 648 ‘eligible’ patients were recruited to the study, of whom 74 were ultimately excluded from the statistical analysis. Of these, 19 in the initial cut and 30 patients in the subsequent cut were excluded for reasons related to inhibitor development/ascertainment, based on information provided in the patients’ disposition flow chart. In the third cut, two individuals had documented inhibitors, but were not included in the final statistics.