Evaluation of ventricular arrhythmias in early clinical pharmacology trials and potential consequences for later development.
This white paper, prepared by members of the Cardiac Safety Research Consortium, discusses several important issues regarding the evaluation of ventricular arrhythmias in early clinical pharmacology trials and their potential consequences for later clinical drug development. Ventricular arrhythmias are infrequent but potentially important medical events whose occurrence in early clinical pharmacology trials can dramatically increase safety concerns. Given the increasing concern with all potential safety signals and the resultant more extensive electrocardiographic monitoring of subjects participating in early phase trials, an important question must be addressed: Are relatively more frequent observations of ventricular arrhythmias related simply to more extensive monitoring, or are they genuinely related to the drug under development? The discussions in this paper provide current thinking and suggestions for addressing this question.
Min
Sherene S
SS
GlaxoSmithKline, Research Triangle Park, NC 27709, USA. sherene.s.min@gsk.com <sherene.s.min@gsk.com>
Turner
J Rick
JR
Nada
Adel
A
DiMino
Tara L
TL
Hynie
Ivo
I
Kleiman
Robert
R
Kowey
Peter
P
Krucoff
Mitchell W
MW
Mason
Jay W
JW
Phipps
Alex
A
Newton-Cheh
Christopher
C
Pordy
Robert
R
Strnadova
Colette
C
Targum
Shari
S
Uhl
Kathleen
K
Finkle
John
J
D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000453:epidemiology / Q000503:physiopathology; D017321:Clinical Trials, Phase I as Topic / Q000592:standards; D003362:Cost-Benefit Analysis; D055808:Drug Discovery; D004562:Electrocardiography; D006801:Humans; D008991:Monitoring, Physiologic; D018579:Patient Selection; D015995:Prevalence; D018570:Risk Assessment; D013686:Telemetry