Assessing proarrhythmic potential of drugs when optimal studies are infeasible.
Assessing the potential for a new drug to cause life-threatening arrhythmias is now an integral component of premarketing safety assessment. International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use Guideline (ICH) E14 recommends the "Thorough QT Study" (TQT) to assess clinical QT risk. Such a study calls for careful evaluation of drug effects on the electrocardiographic QT interval at multiples of therapeutic exposure and with a positive control to confirm assay sensitivity. Yet for some drugs and diseases, elements of the TQT Study may be impractical or unethical. In these instances, alternative approaches to QT risk assessment must be considered. This article presents points to consider for evaluation of QT risk when alternative approaches are needed.
GlaxoSmithKline R&D, King of Prussia, PA 19406-0930, USA. edwin.p.rock@gsk.com
Edwin P
EP
Rock
John
J
Finkle
Howard J
HJ
Fingert
Brian P
BP
Booth
Christine E
CE
Garnett
Stephen
S
Grant
Robert L
RL
Justice
Richard J
RJ
Kovacs
Peter R
PR
Kowey
Ignacio
I
Rodriguez
Wendy R
WR
Sanhai
Colette
C
Strnadova
Shari L
SL
Targum
Yi
Y
Tsong
Kathleen
K
Uhl
Norman
N
Stockbridge
D000818:Animals; D018849:Controlled Clinical Trials as Topic / Q000379:methods; D017277:Drug Approval / Q000458:organization & administration; D004353:Drug Evaluation, Preclinical / Q000379:methods; D015507:Drugs, Investigational / Q000009:adverse effects*; D004562:Electrocardiography / Q000187:drug effects; D006801:Humans; D007391:International Cooperation; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000503:physiopathology
D015507:Drugs, Investigational