The ABC of non-inferiority margin setting: an investigation of approaches

Objectives To assess the efficacy of a new investigative treatment a non-inferiority study is undertaken when it is no longer ethical to have a placebo control. Instead an active controlled trial is undertaken. The objective is thus to show that the new treatment is no worse than the active control. In analysing a non-inferiority trial, the following ABC needs to be considered [1]: 1. The Assay sensitivity of the active control in both the placebo controlled trials and in the active controlled non-inferiority trial is the same. 3. Bias is minimised through steps such as ensuring that the patient population and the primary efficacy endpoint are essentially the same for the placebo-controlled trial and the active-controlled trial. 2. Constancy assumption of the effect of the common comparator. Such that for two trials in sequence: Trial 1 and Trial 2 the control effect of Treatment B vs. Placebo in Trial 1 is assumed to be the same as the control effect of Treatment B vs. ‘Placebo’ in Trial 2 This presentation will describe how this ABC can be considered.