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.
McMahon
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RP
Maryland Psychiatric Research Center, University of Maryland Baltimore, Department of Psychiatry, Baltimore MD 21228, USA. rmcmahon@mprc.umaryland.edu
Harrell
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FE
D015982:Bias; D003627:Data Interpretation, Statistical; D006801:Humans; D015233:Models, Statistical; D009026:Mortality; D011336:Probability; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D016896:Treatment Outcome