Navigation
This page is maintained by the Cardiac Safety
Advisory Board ( Alex
Dmitrienko). Annotated bibliography project
The annotated bibliography lists publications
(papers, book chapters and presentations) that deal with cardiac
safety issues in pharmaceutical applications. Each publication
is accompanied by a brief summary that describes the proposed
methodology and its applications to pharmaceutical research.
Thorough QT studies are recommended in the
ICH E14 guidance document as a definitive tool for assessing the
cardiac repolarization potential of investigational drugs.
Regulatory action was taken and the development
of the ICH E14 guidance on the aspect of cardiac safety and QTc
prolongation initiated following several reports of sudden death
in the marketplace for several drugs associated with QTc prolongation.
Examples of the analysis of QTc data in the
clinical setting.
The length of QT interval is known to be
influenced by a large number of parameters, including heart rate,
age, gender and circadian rhythm. The heart rate is the most influential
of these parameters (QT interval shortens when heart rate is increased
and vice versa). To be able to interpret drug-induced changes
in QT interval, one needs to remove the correlation between the
length of QT interval and heart rate (or RR interval) using a
QT correction method.
Pharmacokinetic-pharmacodynamic modeling
is useful for understanding the results of 'positive' thorough
QTc safety trials, but users should be cautious in the interpretation
of such modeling/learning techniques.
|
