A unifying approach to non-inferiority, equivalence and superiority tests via multiple decision processes

Abstract

Two approaches of multiple decision processes are proposed for unifying the non-inferiority, equivalence and superiority tests in a comparative clinical trial for a new drug against an active control. One is a method of confidence set with confidence coefficient 0.95 improving the conventional 0.95 confidence interval in the producer's risk and also the consumer's risk in some cases. It requires to include 0 within the region as well as to clear the non-inferiority margin so that a trial with somewhat large number of subjects and inappropriately large non-inferiority margin for proving non-inferiority of a drug that is actually inferior should be unsuccessful. The other is the closed testing procedure which combines the one- and two-sided tests by applying the partitioning principle and justifies the switching procedure by unifying the non-inferiority, equivalence and superiority tests. In particular regarding the non-inferiority, the proposed method justifies simultaneously the old Japanese Statistical Guideline (one-sided 0.05 test) and the International Guideline ICH E9 (one-sided 0.025 test). The method is particularly attractive, changing the strength of the evidence of relative efficacy of the test drug against a control at five levels according to the achievement of the clinical trial. The meaning of the non-inferiority test and also the rationale of switching from it to superiority test will be discussed.