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This topic is managed by the Cardiac Safety Advisory Board (Alex Dmitrienko).

Zhang, L., Dmitrienko, A., Luta, G. (2008). Sample size calculations in thorough QT studies. Journal of Biopharmaceutical Statistics. 18, 468-482.

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 cross-over 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.

This section includes SAS code for sample size calculations in the more basic case (under the assumption of a single post-dose time point).

Download the code for performing sample size calculations presented in Table 4 (total sample size in cross-over thorough QT studies with a selected population using Fridericia-corrected QT interval). Note that the sample sizes produced by the program are slightly lower than those given in Table 4 because sample size calculations in the paper were performed using a different package (nQuery Advisor).

This section includes SAS code for general sample size calculations (any number of post-dose time points). The code was written by Anne-Michelle Noone and George Luta (Georgetown University) and utilizes the MVN_DIST macro (Genz adn Bretz, 2002).

Download QTPOWER macro (main macro for performing sample size calculations).
Download example (example of QTPOWER calls).
Download MVN_DIST macro (this macro is used by the QTPOWER macro).

Genz, A., Bretz, F. (2002). Methods for the computation of multivariate t-probabilities. Journal of Computational and Graphical Statistics. 11, 950-971.