QTc-exposure Modeling in Thorough QT Studies
*Xiaoling Meng, sanofi-aventis  *William Wang, Biostatistics and Research Decision Sciences, Merck Research Laboratory, Merck 

Keywords: direct effect, model selection, and PD endpoint selection

Thorough QTc studies are routinely conducted in drug development, and drug effect versus placebo on QT prolongation is analyzed to assess its cardiovascular risk. QTc-exposure modeling and prediction draw increasing interests not only in supporting the primary PD analysis but also in better understanding drug QTc profile and making decisions for future clinical study designs. When a direct exposure-PD relationship holds, a simple direct linear or non-linear model is often fitted. In this presentation, some issues in simple direct modeling are discussed including direct exposure-PD relationship assessment, PD endpoint definition and model selection/evaluation.