An analysis of QTc data collected in four thorough QT studies conducted at Eli Lilly and Company was performed to estimate the variability of the QTc interval and to calculate the variance components related to time-to-time, day-to-day variability, etc. The results were used to develop a sample size calculation framework that enables clinical trial researchers to account for key features of their thorough QT studies, including study design (parallel and crossover designs), number of ECG replicates, number of post-baseline ECG recordings, and subject population (based on subject gender and age). The sample size calculation framework is illustrated using several popular study designs.