Early Drug Discovery Prediction of Proarrhythmia Potential and Its Covariates

Abstract

from different backgrounds introduced the audience to the current safety testing paradigm, the latest achievements within drug safety and remaining hurdles regarding the integration of multiple sources of data acquired both at the preclinical and clinicallevel,andtheirtranslationtothehumaninvivosituation. Despite a reasonable knowledge of the mechanisms related to proarrhythmic cardiotoxicity, there are still questions whether the new paradigm of testing will be able to provide all stakeholders with a sufficient level of confidence with the application of these novel concepts and models to drug safety. This article gives a short overview of the discussed problems, summarizes the discussion, and gives a flavor of a new cardiac safety testing pathway likely to be introduced in the near future. Some of the statements in the text, like the feasibility of the individualized risk assessment, can be contradictory what was left intentionally and shows the line of discussion between speakers. The three leading topics include a description of the molecular and clinical background of drug-induced proarrhythmic effects, a brief presentation of current methods used in the early prediction of such effects together with anticipated changes in the testing paradigm and a discussion of the in vitro–in vivo extrapolation approach, all of which promise the possibility of risk assessment at the individual patient level.