1 SHOULD THE NON-INFERIORITY MARGIN VARY WITH THE COMPARATOR RATE? AN ADAPTIVE STATISTICAL TEST

Choosing the equivalence margin for a non-inferiority trial of an anti-infective medication involves both clinical and statistical considerations. This paper argues that for some trials the equivalence margin should depend on the underlying success rates, rather than being set in advance at a fixed level d. A valid statistical test that adapts d to the underlying success rates is described. When the success rates for comparator drugs are well-established, a test of non-inferiority with a fixed d is appropriate. However, a fixed d may not be justifiable in a situation in which the expected success rates are difficult to estimate, such as for a new indication or for an unusual study design. As elucidated by Swartz[2], many organisms acquire resistance to anti-infective medications so that the success rates of these medications decrease over time. As an example, according to Swartz, “Resistance to penicillin and penicillin-gentamicin synergism led in the late 1970s to widespread use of vancomycin in the treatment of life-threatening enterococcal infections. By the late 1980s vancomycin