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Abstract:
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In testing for non-inferiority of anti-infective drugs, the primary endpoint is often the difference in the proportion of failures between the test and control group at a landmark time. The landmark time is chosen to approximately correspond to a specific historic quantile of the control group, and the non-inferiority margin is selected to be reasonable for that quantile. There is no guarantee that the control quantile from the study will be close to its historic value, and if the landmark time is far from the target control quantile then the pre-specified non-inferiority margin may no longer be reasonable. Exact variable margin tests have been developed by Rohmel and Kieser to address this problem, but these tests can have poor power if the control quantile is far from its historic value. We develop a new variable margin non-inferiority test (and associated R package: nivm) where we continue sampling until a pre-specified proportion of failures have occurred in the control group. Our new test is exact and has power comparable to (or greater than) its competitors when the control quantile from the study equals (or differs moderately from) its historic value.
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