Sir

In their commentary on Casey et al, Boylan and Labovitz raise a number of important issues. The authors first propose that study groups ‘were analyzed separately or in a combination in ways that enhanced the appearance of benefit and reduced the evidence of risk.’ The efficacy analysis reported in the manuscript was the protocol-specified primary analysis. The study was powered to compare the efficacy between monotherapy (olanzapine or risperidone) and combination therapy (divalproex added to one of the two atypical antipsychotics). Two atypicals were chosen to increase the generalizability of the results, and olanzapine and risperidone were specifically chosen based on a studies showing similar efficacy (Davis et al, 2003). Boylan and Labovitz argue that combining antipsychotics in the efficacy analysis was justified on the basis of a test for interaction that was underpowered to detect a difference in a study of this size. The purpose of the test for an interaction in the primary efficacy outcome was to verify no serious departure from the assumption of no difference between antipsychotic groups. However, a visual inspection of the separate antipsychotic groups (Figure 1 in the original study) suggests that the separate antipsychotics were similar in their efficacy (combination therapy is on the favorable side of efficacy at each time point for both drugs by a similar magnitude).

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