The network meta-analytic-predictive approach to non-inferiority trials.

In non-inferiority clinical trials, a test treatment is compared to an active-control rather than to placebo. Such designs are considered when placebo is unethical or not feasible. The critical question is whether the test treatment would have been superior to placebo, had placebo been used in the non-inferiority trial. This question can only be addressed indirectly, based on information from relevant historical trials with data on active-control and placebo. The network meta-analytic-predictive approach to non-inferiority trials is based on a network meta-analysis of the data from the historical trials and the non-inferiority trial, and the prediction of the putative test vs. placebo effect in the non-inferiority trial. The approach extends previous work by incorporating between-trial variability for all relevant parameters and focusing on the parameters in the non-inferiority trial rather than on population means. Two prominent examples with binary outcomes are used to illustrate the approach.