A valid formulation of the analysis of noninferiority trials under random effects meta-analysis

Biostatistics.oxfordjournals.org: 3/30/12

A noninferiority (NI) trial is sometimes employed to show efficacy of a new treatment when it is unethical to randomize current patients to placebo because of the established efficacy of a standard treatment. Under this framework, if the NI trial determines that the treatment advantage of the standard to the new drug (i.e. S−N) is less than the historic advantage of the standard to placebo (S−P), then the efficacy of the new treatment (N−P) is established indirectly. We explicitly combine information from the NI trial with estimates from a random effects model, allowing study-to-study variability in k historic trials. Existing methods under random effects, such as the synthesis method, fail to account for the variability of the true standard versus placebo effect in the NI trial. Our method effectively uses a prediction interval for the missing standard versus placebo effect rather than a confidence interval of the mean.  Read More