title: Group sequential design and analysis of clinical equivalence assessment for generic nonsystematic drug products.
abstract: Clinical trials with therapeutical endpoints are designed with three arms to demonstrate both the efficacy and the equivalence of the test generic treatment and the reference treatment. A generic drug product is determined to be equivalent to the reference drug product if the ratio or difference between the mean responses is bounded within the pre-specified equivalence limits. Often the trials are oversized for the placebo arm. For improvement, we propose a group sequential design with hierarchical testing for the purpose of terminating the placebo arm before testing equivalence between the test and the reference treatments. The hierarchical feature of the proposal will reduce the sample size of the placebo arm and provide treatments to patients in a more efficient manner in a clinical trial setting. After dropping the placebo arm, the option of allocating the planned but unused sample size from the placebo group to the test and reference groups will increase the sample size and power of the equivalence test without inflating the type I error rate by delaying spending it.
authors.affiliation: Office of Biostatistics/Office of Pharmacoepidemiology and Statistical Sciences, Center of Drug Evaluation and Research, US Food and Drug Administration, Rockville, Maryland 20857, USA. TSONG@cder.fda.gov
authors.forename: Yi
authors.initials: Y
authors.lastname: Tsong
authors.forename: Juan Joanne
authors.initials: JJ
authors.lastname: Zhang
authors.forename: Sue Jane
authors.initials: SJ
authors.lastname: Wang
mesh_terms: D002986:Clinical Trials as Topic / Q000379:methods* / Q000592:standards; D016568:Drugs, Generic / Q000592:standards; D013810:Therapeutic Equivalency
chemical_list: D016568:Drugs, Generic