Back to the Top
Can any one please explain the concept of Concentration - QT
modelling which is done in through QT studies. How is the statistical
analysis done for the same.
I have read in the literatures that a linear mixed effect model is
used to assess the effect of concentration on the QT/QTc.
Also, if in a study the plasma concentrations and the ECGs are not
recorded at the same time points then how do we select the timepoints
for the analysis.
Thanks in anticipation.
Vaibhav M. Kerkar
Back to the Top
The following message was posted to: PharmPK
> Can any one please explain the concept of Concentration - QT
> modelling which is done in through QT studies. How is the
> analysis done for the same.
I think it is important to understand that concentration based models
for QT have nothing to do with statistical analysis in the usual
hypothesis testing P value generation sense. Once the modelling has been
done then the results can be applied to test hypotheses.
PKPD models have been used by clinical pharmacologists for decades to
describe the time course of QT changes in relation to plasma
concentrations of drug. In recent years regulatory authorities have
woken up to the idea that perhaps a PKPD model based approach could help
in evaluating pro-arrhythmic risk of drugs.
A regulatory science commentary has appeared recently (Garnett et al
2008) that describes how PKPD models can "used to plan and interpret the
TQT study, to evaluate QT
risk for drugs that have no TQT study, to assess QT risk in
subpopulations, to make dose adjustments, and to write informative drug
labels." [TQT=Thorough QT]
> I have read in the literatures that a linear mixed effect model is
> used to assess the effect of concentration on the QT/QTc.
Most commonly PKPD models will be based on non-linear mixed effect
models because the time course of drug concentration and effects
(usually delayed wrt conc) will nearly always require a non-linear
> Also, if in a study the plasma concentrations and the ECGs are not
> recorded at the same time points then how do we select the timepoints
> for the analysis.
One of the many advantages of a PKPD model approach is that it does not
require sampling for concentrations and QT intervals at the same time.
Garnett CE, Beasley N, Bhattaram VA, Jadhav PR, Madabushi R, Stockbridge
N, et al. Concentration-QT Relationships Play a Key Role in the
Evaluation of Proarrhythmic Risk During Regulatory Review. J Clin
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New
Want to post a follow-up message on this topic?
If this link does not work with your browser send a follow-up message to PharmPK@boomer.org with "Concentration - QT modelling" as the subject
Support PharmPK by using the
Copyright 1995-2011 David W. A. Bourne (email@example.com)