Response to commentary by Dixon and Silman on the systematic review and meta-analysis by Bongartz et al.

A particular advantage of such trials is that there is almost complete follow up of each treatment arm, with patients maintained in the assigned groups for intent-to-treat analysis at least for the randomized portion of the trial, even if drug exposure is discontinued for whatever reason. The appropriate statistical analysis of such comparator groups in the trial context of equivalent follow up in each arm is an odds ratio rather than incidence rate ratio. Dixon and Silman raise the possibility of bias in our analysis because of the greater dropout rate in the placebo arm, potentially leading to a lower detection threshold for malignancies in the placebo compared with the treatment arm. We found no evidence for a difference in detection thresholds in the placebo follow-up period, which was equivalent to the treatment arm in duration for the controlled phase of the studies on which we performed the analysis. Dixon and Silman also note a classification or detection bias for serious infections because of the greater likelihood of placebo patients being hospitalized. In this case our analysis would underestimate the true risk for serious infection in treated compared with control patients.