LAUSR

443 placebo is observed in patient-reported outcomes or subjective measures; the effect of placebo on objective biomarkers or hard outcomes such as mortality are likely minimal.(2) Hence, in this study, when evaluating mortality as primary outcome, we believe that “placebo” and “no treatment” can be considered equivalent and be treated as a common comparator. With regard to differences in effect estimates from direct and indirect comparisons, we acknowledge that for some comparisons, there was a difference in the magnitude of effect observed from head-to-head trials and indirect comparisons from first-order loops. In these instances, congruent with GRADE methodology,(4) we rated the quality of evidence down for intransitivity (or inconsistency in effect estimates from direct and indirect comparisons). Likewise, evidence was rated down for imprecision in effect estimates either due to wide confidence intervals crossing unity or small number of events with failure to achieve optimal information size. This concept encompasses the authors’ concerns regarding reporting P values.