The initial ICH E14 guidance described the thorough QT/QTc (TQT) study with the purpose of evaluating whether a new drug has effects on the QTc interval. Following its adoption, concentration-QTc (C-QTc) modeling was applied to data from TQT studies, and results were comparable with those based on a "by time point" analysis. In 2014, the IQ-CSRC study demonstrated that a small study in healthy subjects using C-QTc as the primary analysis could detect mild drug-induced QTc prolongation. The study led to the revision of the E14 guidance in 2015, allowing the use of C-QTc modeling to exclude a QTc effect at the threshold of concern, 10 ms. The 2015 revision was the starting point for the use of C-QTc modeling applied to data from first-in-human (FIH) studies with the intent to waive requests for a designated TQT study. The 2022 revision (S7B/E14 Q&A) brought non-clinical studies into the decision process for a "definitive" QT evaluation. In this manuscript, the emergence of C-QTc analysis applied to FIH studies with the intent to waive the TQT study is described, and a survey of FDA labels and reviews of approved drugs since 2015 is shared. The uptake has been modest, with only 30% of approved drugs for which a TQT study would be expected using this approach, while a TQT study has been conducted in ∼70% of development programs. It can be expected that the 2022 S7B/E14 revision will increase the number of programs for which a TQT study can be replaced.