About half of the noninferiority trials tested superior treatments: a trial-register based study

A concern that noninferiority (NI) trials pose a risk of degradation of the treatment effects is prevalent. Thus, we aimed to determine the fraction of positive true effects (superiority rate) and the average true effect of current NI trials based on data from registered NI trials. All NI trials carried out between 2000 and 2007 analyzing the NI of efficacy as the primary objective and registered in one of the two major clinical trials registers were studied. Having retrieved results from these trials, random effects modeling of the effect estimates was performed to determine the distribution of true effects. Effect estimates were available for 79 of 99 eligible trials identified. For trials with binary outcome, we estimated a superiority rate of 49% (95% confidence interval = 27–70%) and a mean true log odds ratio of −0.005 (−0.112, 0.102). For trials with continuous outcome, the superiority rate was 58% (41–74%) and the mean true effect as Cohen's d of 0.06 (−0.064, 0.192). The unanticipated finding of a positive average true effect and superiority of the new treatment in most NI trials suggest that the current practice of choosing NI designs in clinical trials makes degradation on average unlikely. However, the distribution of true treatment effects demonstrates that, in some NI trials, the new treatment is distinctly inferior.