An application of this strategy has been reported in which the primary constraint is the quantity of DNA available for study subjects [25]. About 44 per cent of the sample had sufficient DNA to be typed for all markers, with the remaining 56 per cent used for the second stage. An important feature of this study is that the test statistics are calculated over the full sample, with adjustment made for the interim test. This is in contrast to the simpler approach used in the simulation studies [21,23], in which test statistics were calculated separately for the two stages and their p-values combined into an overall significance. Analysing both stages at once[25] makes more efficient use of information and will be the more powerful method for computing significance in the whole sample.
