Thorough QT (TQT) studies: concordance with torsadogenesis and an evolving cardiac safety testing paradigm

Barbara Wiśniowska; Zofia Tylutki; Sebastian Polak

doi:10.1016/j.drudis.2017.04.017

Thorough QT (TQT) studies: concordance with torsadogenesis and an evolving cardiac safety testing paradigm

Drug Discov Today. 2017 Oct;22(10):1460-1465. doi: 10.1016/j.drudis.2017.04.017. Epub 2017 May 13.

Authors

Barbara Wiśniowska¹, Zofia Tylutki², Sebastian Polak³

Affiliations

¹ Pharmacoepidemiology and Pharmacoeconomics Unit, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, Str., 30-688 Krakow, Poland. Electronic address: b.wisniowska@uj.edu.pl.
² Pharmacoepidemiology and Pharmacoeconomics Unit, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, Str., 30-688 Krakow, Poland.
³ Pharmacoepidemiology and Pharmacoeconomics Unit, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, Str., 30-688 Krakow, Poland; Simcyp (part of Certara), Sheffield S2 4SU, UK.

PMID: 28511997
DOI: 10.1016/j.drudis.2017.04.017

Abstract

Since 2005, when the International Conference on Harmonisation (ICH) E14 guideline was adopted, no drug has been withdrawn because of QTc prolongation or torsade de pointes arrhythmia. There are, however, costs associated with this success. In addition to the time and money invested, thorough QT (TQT) studies have limited the efficiency of the drug development pipeline. In this paper, we discuss the relevance of TQT trials as a tool for proarrhythmic risk prediction as a part of the debate regarding their usefulness.

Publication types

Review

MeSH terms

Arrhythmias, Cardiac / drug therapy
Arrhythmias, Cardiac / physiopathology
Drug Discovery / methods
Heart / drug effects
Heart / physiopathology*
Humans
Long QT Syndrome / drug therapy
Long QT Syndrome / physiopathology*
Pharmaceutical Preparations / administration & dosage

Substances

Pharmaceutical Preparations