title: Exposure-response modeling approach for assessing QT effect in "thorough" QT/QTc studies.
abstract: We assess the QT effect using an exposure-response model in a "thorough QT/QTc study" with a four-period crossover design in which the treatments are placebo, positive control, higher dose of investigational drug, and therapeutic dose of investigational drug. In the study, QTc interval values and the drug concentrations are obtained for several specified times during treatment. This approach to the assessment of non-inferiority of the higher dose to placebo is an alternative strategy suggested in ICH-E14 guideline (Section 2.2.5) to the intersection-union test.
authors.affiliation: Northern Illinois University, DeKalb, Illinois, 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: D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D003198:Computer Simulation; D018592:Cross-Over Studies; D003627:Data Interpretation, Statistical; D004562:Electrocardiography / Q000706:statistics & numerical data; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D016014:Linear Models; D015233:Models, Statistical; D009010:Monte Carlo Method; D015990:Placebo Effect; D013997:Time Factors