Research On Drug-induced Tosade De Points Risk Management

Drug-induced Torsade De Pointes (TdP) is life-threatening Serious AdverseEvent (SAE). It is characterized by acute onset, rapid progress, and high mortality.About20%TdP cases result in ventricular fibrillation and sudden cardiac death.Unacceptable TdP risk is one of the most common reasons that drugs were withdrawnfrom the market in recent years. Currently, in China, the research on TdP risk is stillat its preliminary stage.This study is focus on drug-induced TdP risk early prediction, identification,survey, assessment and treatment throughout the entire life cycle of the drug in orderto minimize the risk and increase the safety of drug. This research establishedsystemic strategy to predict, indentify and prevent drug-induced TdP utilizing statisticanalysis, modeling, data mining, Analytic Hierarchy Process，clinical research, drugepidemiology and empirical research.During early stage of new drug development: we build up a scientific model topredict the risk of TdP, which is used to screen and evaluate the risk of drug-inducedTdP. The model will provide the pharmaceutical manufacturers decision making toprevent high-risk drug from entering the clinical research stage and eventuallyentering the market, and to avoid its potential harm to the subjects in trials and/or thepatients, and at the same time it will save the drug-developing companies valuablemanpower, resources, money and time.During the clinical research stage: we establish drug-induced QT/QTc or TdPspecific risk indentifying clinical research protocol, based on the principle of ICH E14guidance regarding thorough QT study which was released in2005and integrating theexperience from numbers of overseas completed studies after the implementation ofthe guidance. We also propose TQT alternative approach to assess proarrhythmicpotential of drugs when optimal studies are infeasible, such as botanical drug andoncology drug. Using the strategy during clinical research stage, we provide thepharmaceutical manufacturers and drug administration Agency support to furtherprevent high-risk drug entering the market.During the postmarking period: we investigate the risk factors associated withdrug-induced TdP in clinical practice, and establish the risk evaluation model. In theresearch，we also point out the current problem during medical care. We developedTdP prevention strategy to instruct medical-care providers to formulate rational implementation scheme and raise awareness during practice to prevent and mitigatedrug-induced TdP risk.At the end of the study, an empirical research is implemented to validate thestrategy we established.The research on drug-induced TdP risk has important practical significance andtheoretical value for ensuring the safety of drug administration, optimizing the societymedical recourses distribution and providing the Agency and drug-developingcompanies decision support.