A new procedure for testing equivalence in comparative bioavailability and other clinical trials

The problem of testing for equivalence in clinical trials is restated here in terms of the proper clinical hypotheses and a simple classical frequentist significance test based on the central t distribution is derived. This method is then shown to be more powerful than the methods based on usual (shortest) and symmetric confidence intervals. We begin by considering a noncentral t statistic and then consider three approximations to it. A simulation is used to compare actual test sizes to the nominal values in crossover and completely randomized designs. A central t approximation was the best. The power calculation is then shown to be based on a central t distribution, and a method is developed for obtaining the sample size required to obtain a specified power. For the approximations, a simulation compares actual powers to those obtained for the t distribution and confirms that the theoretical results are close to the actual powers.

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