title: The joint modeling of drug and positive control effects to estimate sample size and power in crossover "thorough" QT/QTc studies.
abstract: We present analytical results for computing the power and sample size in a thorough QT/QTc study with a four-period crossover design in which the treatments are placebo, positive control, supratherapeutic dose of investigational drug, and therapeutic dose of investigational drug. An assessment of noninferiority of the supratherapeutic dose to placebo is performed by the intersection-union test and assay sensitivity is tested (union-intersection test) at prespecified time points using positive control within the framework of a linear mixed-effects analysis. The power and sample size estimates are obtained using the joint distribution of statistics to test noninferiority of the supratherapeutic dose to placebo and to test assay sensitivity using positive control.
authors.affiliation: Division of Statistics, Northern Illinois University, DeKalb, IL 60115, USA. bala@math.niu.edu
authors.forename: Balakrishna
authors.initials: B
authors.lastname: Hosmane
authors.forename: Charles
authors.initials: C
authors.lastname: Locke
authors.forename: Yi-Lin
authors.initials: YL
authors.lastname: Chiu
mesh_terms: D002986:Clinical Trials as Topic / Q000379:methods / Q000706:statistics & numerical data; D018592:Cross-Over Studies; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis / Q000453:epidemiology; D015507:Drugs, Investigational / Q000009:adverse effects*; D004562:Electrocardiography / Q000706:statistics & numerical data; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D015233:Models, Statistical; D018401:Sample Size; D016008:Statistical Distributions
chemical_list: D015507:Drugs, Investigational