Tests of one-sided versus two-sided hypotheses in placebo-controlled clinical trials

The p value associated with a test of significance is supposed to represent the probability of observed results given that the null hypothesis is actually true. In evaluating the efficacy of a new drug against placebo, regulatory considerations focus on superiority of the new drug over placebo. The disapproval consequence of placebo superiority is no different from the disapproval consequence of equivalence between drug and placebo. It is furthermore inconceivable that a drug company will submit a New Drug Application claiming superior efficacy for placebo. Thus, the only probability of concern is the probability that apparent superiority of drug over placebo is a chance finding, and that is the probability associated with a one-tailed test. Where multiple studies must be evaluated with regard to the regulatory decision, meta-analytic considerations further support the relevance of one-sided p values.