NONINFERIORITY STUDIES WITH MULTIPLE NEW TREATMENTS AND HETEROGENEOUS VARIANCES

摘要

The objective of a noninferiority (NI) trial is to affirm the efficacy of a new treatment compared with an active control by verifying that the new treatment maintains a considerable portion of the treatment effect of the control. Compensation by benefits other than efficacy is usually the justification for using a new treatment, as long as the loss of efficacy is within an acceptable margin (NI margin) from the standard treatment. A popular approach is to express this margin in terms of the efficacy difference between the new treatment and the active control. Based on this approach and the realization that NI trials often comprise several new treatments, statistical procedures that simultaneously conduct NI tests of several new treatments have been developed. However, these procedures rely on the assumption that the variances of the treatments are homogeneous. In this article, we discuss the undesirable effect of using these procedures on the familywise Type I error rate when the treatment responses have heterogeneous variances. To alleviate this problem, we reveal potential procedures that are more appropriate. Further, a power study is conducted to compare the different procedures to provide guidance on the selection of adequate testing procedures in NI trials. Clinical examples are given for illustrative purposes.