title: Evaluation of ventricular arrhythmias in early clinical pharmacology trials and potential consequences for later development.
abstract: 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.
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC 27709, USA. sherene.s.min@gsk.com <sherene.s.min@gsk.com>
authors.forename: Sherene S
authors.initials: SS
authors.lastname: Min
authors.forename: J Rick
authors.initials: JR
authors.lastname: Turner
authors.forename: Adel
authors.initials: A
authors.lastname: Nada
authors.forename: Tara L
authors.initials: TL
authors.lastname: DiMino
authors.forename: Ivo
authors.initials: I
authors.lastname: Hynie
authors.forename: Robert
authors.initials: R
authors.lastname: Kleiman
authors.forename: Peter
authors.initials: P
authors.lastname: Kowey
authors.forename: Mitchell W
authors.initials: MW
authors.lastname: Krucoff
authors.forename: Jay W
authors.initials: JW
authors.lastname: Mason
authors.forename: Alex
authors.initials: A
authors.lastname: Phipps
authors.forename: Christopher
authors.initials: C
authors.lastname: Newton-Cheh
authors.forename: Robert
authors.initials: R
authors.lastname: Pordy
authors.forename: Colette
authors.initials: C
authors.lastname: Strnadova
authors.forename: Shari
authors.initials: S
authors.lastname: Targum
authors.forename: Kathleen
authors.initials: K
authors.lastname: Uhl
authors.forename: John
authors.initials: J
authors.lastname: Finkle
mesh_terms: 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