Risks encountered when not adjusting for diurnal variation and food effect in QTcF analysis based on Phase I data

MIDD

Pharmacometrics

Methodology

J Pharmacokinet Pharmacodyn. 2026 Feb;53(1):6.

Bardol M, Sarr C, Henrich A, Mezzalana E, Langenhorst J

About the publication

Phase I studies are increasingly used to assess drug QT liability—the risk that a compound may prolong the QT interval on an electrocardiogram (ECG). This measurement serves as a critical indicator of cardiac risk and represents a fundamental safety concern in drug development.

However, these early-phase trials often lack the strict controls for meal intake and sampling times found in dedicated "thorough QT" (TQT) studies. Without such standardization, significant variability can be introduced, potentially masking or exaggerating the perceived proarrhythmic risk.

This latest publication, authored by Maddlie Bardol, Andrea Henrich, Céline Sarr, Enrica Mezzalana, and Jürgen Langenhorst in the Journal of Pharmacokinetics and Pharmacodynamics, uses simulation analysis to examine how the uncontrolled factors affect the reliability of concentration-QTc modeling.

About the publication

Key conclusions include