Without a placebo arm, any non-inferiority inference involving assessment of the placebo effect under the active control trial setting is difficult. The statistical risk for falsely concluding non-inferiority cannot be evaluated unless the constancy assumption approximately holds that the effect of the active control under the historical trial setting where the control effect can be assessed carries to the noninferiority trial setting. The constancy assumption cannot be checked because of missing the placebo arm in the non-inferiority trial. Depending on how serious the violation of the assumption is thought to be, one may need to seek an alternative design strategy that includes a cushion for a very conservative non-inferiority analysis or shows superiority of the experimental treatment over the control. Determination of the non-inferiority margin depends on what objective the non-inferiority analysis is intended to achieve. The margin can be a fixed margin or a margin functionally defined. Between-trial differences always exist and need to be properly considered.