On non-inferiority margin and statistical tests in active control trials.
The problem of selecting a non-inferiority margin and the corresponding statistical test for non-inferiority in active control trials is considered. For selection of non-inferiority margin, the guideline by the International Conference on Harmonization (ICH) recommends that the non-inferiority margin should be chosen in such a way that if the non-inferiority of the test therapy to the active control agent is claimed, the test therapy is not only non-inferior to the active control agent, but also superior to the placebo. Furthermore, variability should be taken into account. Along this line, a method for selecting non-inferiority margins with some statistical justification is proposed. Statistical tests for non-inferiority designed in the situation where the non-inferiority margin is an unknown parameter are derived. An example concerning a cancer trail for testing non-inferiority with the primary study endpoint of the time to disease progression is presented to illustrate the proposed method.
Chow
Shein-Chung
SC
Millennium Pharmaceuticals, Inc., Cambridge, MA 02139, USA.
Shao
Jun
J
D000970:Antineoplastic Agents; D004341:Drug Evaluation / Q000379:methods*; D017408:Guidelines as Topic; D006801:Humans; D015233:Models, Statistical; D010919:Placebos; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design
D000970:Antineoplastic Agents; D010919:Placebos