Seminar
Brian Smith
Covariate-Adjusted Analysis of QT Interval: Population and Individualized Corrections
Over the last ten years one of the leading causes of removal of a drug from the market by the Food and Drug
Administration has been due to drug induced torsade de pointes (TdP), a cardiac arrhythmia that can lead
to sudden death. A feature of TdP is a pronounced prolongation of the QT interval. Although imperfect in
its predictiveness, many believe that drugs that increase QT interval by 10 msec or more may have an
unacceptably high risk of causing TdP. For this reason it is paramount for pharmaceutical companies and
regulators to understand a drugs impact on the QT interval. Unfortunately, however, there are many issues
that cloud our ability to draw reliable inference from the analysis of this endpoint. One of those issues
deals with the fact that QT interval is inversely related to heart rate. This causes particular analytical
concerns for drugs that increase heart rate. This talk will focus on this issue and propose methods that
seem to fix most concerns.
