Sample size for equivalence trials: A case study from a vaccine lot consistency trial

For some trials, simple but subtle assumptions can have a profound impact on the size of the trail. A case in point is a vaccine lot consistency (or equivalence) trial. Standard sample size formulas used for lot consistency trials rely oil only one component of variation, namely, the variation in antibody titers within lots. The other component the variation in the means of titers between lots, is assumed to be equal to zero. In reality, some amount of variation between lots, however small, will be present even under the best manufacturing practices. Using data from a published lot consistency trial, we demonstrate that when the between-lot variation is only 0.5 per cent of the total variation, the increase in the sample size is nearly 300 per cent when compared with the size assuming that the lots are identical. The increase in the sample size is so pronounced that in order to maintain power one is led to consider a less stringent both components of variation is provided. We also due to correlated comparisons arising from tree pairs of lots as a function of the between-lot variance. Copyright (C) 2008 John Wiley & Sons, Ltd.