New confidence bounds for QT studies

Abstract

The proposed guidelines for the assessment of the effect of new pharmaceutical agents on the QT interval (beginning of QRS complex to end of T wave on the electrocardiogram) are based on the maximum of a series over time of simple one-sided 95 per cent upper confidence bounds. This procedure is typically very conservative as a procedure for obtaining a 95 per cent bound for the maximum of the population parameters. This paper proposes new bounds for the maximum, both analytical and bootstrap-based, that are lower but still achieve correct coverage in the context of crossover and parallel designs for the most realistic portions of the parameter space.