Investigating Drug-Induced QT and QTc Prolongation in the Clinic: A Review of Statistical Design and Analysis Considerations: Report from the Pharmaceutical Research and Manufacturers of America QT Statistics Expert Team

The dangers inherent to the public via the use of drugs known to prolong the QT and QTc interval such as terfenadine and cisapride call for a careful evaluation of this potential in drug development. Methods in development for this assessment in preclinical and clinical development are reviewed, and statistical issues in the design and analysis of clinical trials used to assess this potential are described. Methods, measurement, and analysis are illustrated using data from clinical trials, and issues in the analysis and interpretation of data are developed. It is recommended that the statistical rigor of the International Conference on Harmonisation guidance currently in development for clinical assessment be enhanced and that further research be conducted in the choice of endpoints, testing of hypotheses, and interpretation of QT and QTc data.