If a trial intended to demonstrate efficacy by showing superiority of a test intervention to control lacks assay sensitivity, it will fail to show that the test intervention is superior and will fail to lead to a conclusion of efficacy.
In contrast, if a trial intended to demonstrate efficacy by showing a test intervention is non-inferior to an active control lacks assay sensitivity, the trial may find an ineffective intervention to be non-inferior and could lead to an erroneous conclusion of efficacy.
For instance, if there is reliable and reproducible evidence from previous superiority trials of an effect size of 10% for a control intervention compared to placebo, an appropriately designed non-inferiority trial designed to rule out that the test intervention may be as much as 5% less effective than the control would have assay sensitivity.
In addition, a valid noninferiority trial is not possible in situations in which there is a lack of data demonstrating a reliable and reproducible effect of the control compared to placebo.
In addition to choosing a margin based upon credible past evidence, to have assay sensitivity, the planned non-inferiority trial must be designed in a way similar to the past trials which demonstrated the effectiveness of the control compared to placebo, the so-called "constancy assumption".