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

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