Study Design and Statistical Evaluation of QT Prolongation

The ICH E14 guideline provides recommendation to assess QT interval prolongation and proarrhythmic potential of non-antiarrhythmic drugs in clinical studies. As there exist many statistical issues in the clinical evaluation of QT prolongation, electrocardiograms, background information of the guideline and QT interval correction methods are described for introduction. Because of the inverse relationship to heart rates, QT intervals are corrected for heart rates in order to obtain a variable which is independent of heart rate. Population-derived correction, subject-specific correction, and other correction methods are introduced. Assumptions of each correction method and its properties are discussed. Study design should be considered to collect appropriate data and estimate accurate heart rate correction formulae.