Global Two-Group Multiple Endpoint Adjustment Methods Applied to Clinical Trials

Abstract

Often, clinical trial results are reported and used for claiming a treatment effect without adjusting for the multiplicity arising from the presence of multiple endpoints. It is well recognized that this practice is likely to inflate the type I error rate unless the endpoints are highly correlated. To control such an inflation of the type I error rate, two approaches, both appropriate on their own grounds, are in use. One is the ‘global’ approach which aims at demonstrating overall treatment effect and considers all given endpoints simultaneously. The other approach, often called the ‘endpoint-specific’ approach, assesses significance for each endpoint separately, assuring meaningful control of the overall type I error rate. This paper addresses and discusses some of these global multiple endpoint adjustment methods in the context of clinical trial applications where two treatments are being compared (for example, active treatment with a placebo), and gives some simulation results to assess their performance regarding the α-level protection and power.