A Pathway For Replacing Costly TQT Studies

By Borje Darpo, M.D., Ph.D. – Chief Scientific Officer, Cardiac Safety at Clario

As described in the International Conference for Harmonization (ICH) E14 guidance document, as part of cardiovascular risk assessments, all new drugs are required to undergo testing for potential effects on electrocardiogram (ECG) parameters. In the initial version of the E14 guidance document, designated studies were described as a thorough QT (TQT) study, in which the potential impact of high doses of a new drug on the corrected QT interval (QTc) interval of healthy subjects was evaluated alongside that of a positive control group.

However, thanks to new studies and increased experience by regulators and drug developers, this process approach has been revised. In a small study sponsored by Clario, known as the IQ-CSRC Study, researchers found that the evaluation of potential QTc effect could be completed with a concentration-QTc (C-QTc) analysis—and without a positive control if sufficiently high concentrations of the drug were previously studied. Additionally, the recently approved S7B/E14 Q&A document has only further encouraged the adoption of early-stage C-QTc analysis.

Access the full article to learn how implementing the ECG technique, EPQT, into the design of early clinical studies in healthy subjects represents an efficient and cost-effective approach, providing an excellent opportunity to replace the TQT study.