title: TACT method for non-inferiority testing in active controlled trials.
abstract: In active controlled trials without a placebo arm, non-inferiority testing is often considered but has different objectives. For the objective of demonstrating the efficacy of an experimental treatment or retention of a fraction of the control effect by the treatment, there are two types of statistical methods for testing - the synthesis method and the confidence interval method. According to the study of Wang, Hung and Tsong, the former is efficient under the so-called constancy condition but may have the alpha error rate inflate rapidly if the condition does not hold. In contrast, the latter method with careful selection of the non-inferiority margin tends to be conservative if the condition holds and may still have a valid alpha error otherwise unless the effect of the active control is less to a large extent in the active controlled trial than in the historical trials. We developed the TACT method, Two-stage Active Control Testing, as a viable compromise between the two methods. Through the TACT method, the uninterpretable non-inferiority testing may be avoided prior to the end of the trial. The TACT method carefully constructed can have a valid alpha error rate and the power close to the synthesis method if the constancy condition holds. In addition, the TACT method is more powerful than the confidence interval method for testing for the efficacy of the new treatment relative to the putative placebo and for showing that the new treatment is not inferior to the active control comparator.
authors.affiliation: Division of Biometrics II, OB/OPaSS/CDER/FDA, Rockville, MD 20857, USA. wangs@cder.fda.gov
authors.forename: Sue-Jane
authors.initials: SJ
authors.lastname: Wang
authors.forename: H M James
authors.initials: HM
authors.lastname: Hung
mesh_terms: D016001:Confidence Intervals; D018849:Controlled Clinical Trials as Topic / Q000379:methods*; D004341:Drug Evaluation / Q000379:methods*; D006801:Humans; D009010:Monte Carlo Method; D010919:Placebos; D012107:Research Design; D013223:Statistics as Topic
chemical_list: D010919:Placebos