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Assessment of equivalence on multiple endpoints
Author(s) -
Quan Hui,
Bolognese Jim,
Yuan Weiying
Publication year - 2001
Publication title -
statistics in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.996
H-Index - 183
eISSN - 1097-0258
pISSN - 0277-6715
DOI - 10.1002/sim.985
Subject(s) - equivalence (formal languages) , clinical endpoint , confidence interval , medicine , clinical trial , computer science , intersection (aeronautics) , mathematics , statistics , discrete mathematics , engineering , aerospace engineering
Abstract Some clinical trials aim to demonstrate therapeutic equivalence on multiple primary endpoints. For example, therapeutic equivalence studies of agents for the treatment of osteoarthritis use several primary endpoints including investigator's global assessment of disease activity, patient's global assessment of response to therapy, and pain. In this paper, thoughts on simultaneous equivalence assessment on three endpoints are presented. As pointed out by Berger and Hsu (1996), the conventional intersection‐union test can be conservative. Simulation and computation are conducted to provide an insight on the conservativeness. We also provide a method to lower the confidence level and at the same time maintain the type I error when endpoints have normal distributions and are independent. If, in a particular analysis, the goal is to demonstrate equivalence on as many endpoints as possible, a step‐up procedure can be used for selecting those endpoints for which equivalence may be demonstrated. This step‐up procedure at the same time controls experimentwise error rate. The techniques are illustrated by a data example. Copyright © 2001 John Wiley & Sons, Ltd.