Thorough QT/QTc study

Darpo B (2010) The thorough QT/QTc study four years after the implementation of the ICH E14 1452 guidance. Br J Clin Pharmacol 159(l) 49-57 

Table 3.4 Problems encountered in conducting the thorough QT/QTc study in adult healthy volunteers.

Zhang J, Machado SG (2008) Statistical issues including design and sample size calculation in thorough QT/QTc studies. J Biopharm Stat 18 451 67 

FDA established its QT interdisciplinary review team (IRT), which reviews protocols and study reports for thorough QT/QTc studies and advises review divisions accordingly 

Taubel J, Naseem A, Harada T et al (2010) Levofloxacin can be used effectively as a positive control in thorough QT/QTc studies in healthy volunteers. Br J Clin Pharmacol 69 391-400 Taubel J, Wong AH, Naseem A, Ferber G, Camm AJ (2012) Shortening of the QT interval after food can be used to demonstrate assay sensitivity in thorough QT studies. J Clin Pharmacol 52 1558-1565 

Table 7.1 Timeline of important events in the evolution and employment of the thorough QT/QTc study as described in ICH Guideline E14

Bouvy JC, Koopmanschap MA, Shah RR, ScheUekens H (2012) The cost-effectiveness of drug regulation the example of thorough QT/QTc studies. Qin Pharmacol Ther 91 281-288 

Salvi V, Karnad DR, Kerkar V et al (2014) Comparison of two methods of estimating reader variability in QT interval measurements in thorough QT/QTc studies. Ann Noninvasive Electrocardiol 19 182-189 

Sun GG, Quan H, Kringle R, Meng Z (2012) Comparison of statistical models adjusting for baseline in the analysis of parallel-group thorough QT/QTc studies. J Biopharm Stat 22 438-462 

The Proarrhythmic Cardiac Safety Regulatory Landscape Circa 2005-2015 Drug-Induced hERG Channel Block and the Thorough QT/QTc Study 

Another unanswered question is the evaluation of the effect on cardiac repolarization of oncologic drugs, for which the thorough QT/QTc study in volunteers cannot be performed [166], In these cases, not only central tendency (i.e. mean QTc increase) and proportion of outliers but also other findings such as syncope, ventricular tachyarrhythmias and other cardiac effects should be more closely defined. 

Davy M, Upward J, Arumugham T et al (2013) Cmdiac repoleuization with gabapentin enacarbil in a randomized, double-bhnd, placebo- and active-controlled, crossover thorough QT/QTc study in healthy adults. Clin Ther 35 1964—1974 

Sano M, Aizawa Y, Katsumata Y et al (2014) Evaluation of differences in automated QT/QTc measurements between Fukuda Denshi and Nihon Koden systems. PLoS One 9 e 106947 Satin LZ, Durham TA, Turner JR (2011) Assessing a dmg s proarrhythmic liability an overview of computer simulation modeling, nonclinical assays, and the thorough QT/QTc Study. Drug Inf J 45 357-375 

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