Non-inferiority frontiers
arc-sine transformation
EVENT
While choosing the non-inferiority frontier, several considerations were made. First, as previously proposed, we considered the possibility to use the power-stabilising frontier, which is based on the arc-sine transformation [Defining a frontier where the non-inferiority margin varies from the originally proposed 10 percentage point difference has some costs in terms of power; hence, we would define a frontier that only changes the non-inferiority margin within the range where the control event risk is reasonably likely to lie.We decided not to consider changing the non-inferiority margin for larger-than-expected event risks, as a control viral rebound risk (confirmed viral rebound >  = 50c/mL) larger than 12% was considered highly unlikely.We considered the originally selected non-inferiority margin of 10 percentage points reasonable for control event risk at or above 9%.In discussions with clinical colleagues, we chose to fix the non-inferiority margin at 5 percentage points for 1% control event risk and at 8 percentage points for 5% control event risk.These led us to consider the following frontiers, which are all plotted in Fig. Non-inferiority frontiers considered for the D3 trial. The grey line indicates the 10% risk difference margin and the three stars are the points at which the non-inferiority margin was agreed in discussion with clinicians