Concentration‐QT Relationships Play a Key Role in the Evaluation of Proarrhythmic Risk During Regulatory Review 论文

摘要

The criterion for assessing whether a drug prolongs QT as described in the International Conference on Harmonization topic E14 guideline does not explicitly account for individual drug concentrations. The authors' experience with reviewing QT studies indicates that understanding the relationship, if any, between individual drug concentration and QT change provides important additional information to support regulatory decision making. Therefore, regulatory reviews of "thorough QT" studies routinely include a characterization of the concentration-QT relationship. The authors provide examples to illustrate how the concentration-QT relationship has been used to plan and interpret the thorough QT study, to evaluate QT risk for drugs that have no thorough QT studies, to assess QT risk in subpopulations, to make dose adjustments, and to write informative drug labels.