2019 PharmSci 360
In response to drug-induced torsades de pointes (TdP), thorough QT study was introduced in 2005 to determine if a drug has an effect on QTc prolongation and to inform the intensity of ECG monitoring in late-stage clinical trials. Extensive research was undertaken to apply pharmacometrics analyses to expand the flexibility in QT study design and to predict the QTc effect from early phase clinical trials. Sub-optimal design and inappropriate use of exposure-response analysis plan have been seen in regulatory submissions, which could otherwise help accelerate the clinical development program of new drugs. This presentation will provide an overview of scientific considerations and regulatory perspectives for using exposure-response analysis as the primary analysis for QT assessment. Case studies with different effect sizes, study designs, and product features will be discussed.