According to the code of federal regulation , clinical investigations of a drug distinguish the effect of a drug from other influences through adequate and well-controlled clinical investigation. Randomized, double blind, placebo or active controlled trials are the gold standard. However, due to ethical concern or infeasibility, non-inferiority trials or single arm historical controlled trials are conducted. Inferences from these trials involve historical trials which could be substantially different from non-inferiority trials or single arm historical controlled trials, leading to potentially biased assessment therefore inadequate conclusions. In the presentation, we review statistical approaches developed to reduce the bias.