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Estimation of the Power of the Food Effect on QTc to Show Assay Sensitivity
Author(s) -
Ferber Georg,
Fernandes Sara,
Täubel Jörg
Publication year - 2018
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.975
Subject(s) - sensitivity (control systems) , qt interval , meal , assay sensitivity , positive control , food and drug administration , medicine , control (management) , statistics , pharmacology , econometrics , mathematics , computer science , engineering , traditional medicine , artificial intelligence , pathology , alternative medicine , electronic engineering
The most recent International Conference on Harmonisation E14 Q&A document states that a separate positive control would not be necessary provided sufficiently high exposures are achieved in the early‐phase studies. Realistically, a phase 1 study is unlikely to include a pharmacological positive control, and in cases in which plasma levels of the drug exceeding therapeutic levels are not achieved, the lack of a positive control can constitute a limitation when excluding an effect of regulatory concern. It has been proposed to use the effect of a standardized meal on the estimate of the diurnal time course of QTc to show assay sensitivity. We conducted simulations by subsampling subjects from a 3 different studies and could show that the effect on food on QTc can be reliably prove assay sensitivity for sample sizes as low as 3 × 6 subjects with a power greater than 80%.