Abstract
Objective
To present and compare three statistical approaches for analyzing a noninferiority
trial when the noninferiority margin depends on the control event rate.
Study design and setting
In noninferiority trials with a binary outcome, the noninferiority margin is often
defined as a fixed δ, the largest clinically acceptable difference in event rates
between treatment groups. An alternative and more flexible approach is to allow δ
to vary according to the true event rate in the control group. The appropriate statistical
method for evaluating noninferiority with a variable noninferiority margin is not
apparent. Three statistical approaches are proposed and compared: an observed event
rate (OER) approach based on equating the true control rate to the observed rate,
a Bayesian approach, and a likelihood ratio test.
Results and conclusions
Simulations studies indicate that the proportion of trials in which noninferiority
was erroneously demonstrated was higher for the OER approach than with the Bayesian
and likelihood ratio approaches. In some cases, the Type I error rate exceeded 10%
for the OER approach. The OER approach is not recommended for the analysis of noninferiority
trials with a variable margin of equivalence. The Bayesian and likelihood ratio methods
yielded better operating characteristics.
Keywords
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Article info
Publication history
Accepted:
May 28,
2004
Footnotes
Supported by National Institute of Health grant nos. UO1 AR42540-03 and P30 CA13330.
Identification
Copyright
© 2004 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
