Since the implementation of the International Conference on Harmonization (ICH) E14 guideline in 2005, regulators have required a ‘Thorough QTc’ (TQT) study for evaluating the effects of investigational drugs on delayed cardiac repolarization as manifested by a prolonged QTc interval. However, TQT studies have increasingly been viewed unfavorably due to their low cost-effectiveness. Several researchers have noted that a robust drug concentration-QTc (conc-QTc) modeling assessment in early phase development should, in most cases, obviate the need for a subsequent TQT study. In December 2015, ICH released an ‘E14 Q&As (R3)’ document supporting the use of conc-QTc modeling for regulatory decisions. In this presentation, we propose a simple improvement of two popular conc-QTc assessment methods for typical first-in-human crossover-like single ascending dose clinical pharmacology trials. The improvement is achieved, in part, by leveraging routinely encountered (and expected) intra-subject correlation patterns encountered in such trials. A real example involving a single ascending dose and corresponding TQT trial, along with results from a simulation study, illustrate the strong performance of the proposed method. The improved conc-QTc assessment will further enable highly reliable go/no-go decisions in early phase clinical development and deliver results that support subsequent TQT study waivers by regulators.