Comparison of non-inferiority frontiers
overinflation
EVENT
Here we compare the operating characteristics of different non-inferiority frontiers, analysed using the “Modify significance level if change non-inferiority margin” method. We planned to compare the stepped, steep, and linear frontiers to the SAFE frontier in terms of power and type 1 error for each possible true value of control event risk in the range considered.When using the “Modify significance level if change non-inferiority margin” method, the first thing to do is to find the lower significance level that could control type 1 error for each frontier. While changing the significance level to 0.005 when changing the non-inferiority margin was enough for the SAFE and linear frontiers, it still did not control type 1 error for the stepped and steep frontiers. In fact, no reasonable significance level, i.e. no significance level that could maintain reasonable power, or no significance level higher than 0.00005, was enough to analyse the trial data controlling type 1 error using either the stepped or steep frontier. As an example, Fig. Type 1 error rate at different values of true control event risk when using the stepped frontier with the “modify significance level if change margin” method with different lower significance levelsFigure Comparison of power for analysing D3 using the linear or SAFE non-inferiority frontiers with different true control event risksNote that the slight overinflation of type 1 error for very small event risks is not due to the use of frontiers, but rather to known limitations of Wald confidence intervals for very low event risks.