Joint testing of mortality and a non-fatal outcome in clinical trials.

The following procedures are proposed for clinical trials of potentially lethal diseases with a non-fatal primary outcome: (i) comparison of treatments on worst-rank scores combining mortality and the non-fatal outcome; (ii) testing first for mortality differences, and then for differences on the worst-rank scoring if there is no significant evidence for mortality differences. Power and control of type I error rate while testing mortality and worst-rank scores by Bonferroni or closed testing procedures are compared. Used together these procedures improve power to detect treatments with favourable effects on both mortality and the designated non-fatal outcome, while reducing the likelihood of declaring that a treatment benefits patients when undetected adverse effects on mortality are present. Copyright 2001 John Wiley & Sons, Ltd.