title: Dealing with global safety issues : was the response to QT-liability of non-cardiac drugs well coordinated?
abstract: Drug-induced torsade de pointes (TdP) is a potentially fatal iatrogenic entity. Its reporting rate in association with non-cardiac drugs increased exponentially from the early 1990s and was associated with an increasing number of new non-cardiac drugs whose proarrhythmic liability was not appreciated pre-marketing. This epidemic provoked a comprehensive global response from drug regulators, drug developers and academia, which resulted in stabilization of the reporting rate of TdP. This commentary reviews the chronology and nature of, and the reasons for, this response, examines its adequacy, and proposes future strategies for dealing with such iatrogenic epidemics more effectively. It is concluded that the response was piecemeal and lacked direction. No one entity was responsible, with the result that important contributions from regulators, industry and academia lacked coordination. While the process of dealing with QT crisis seemed to have worked reasonably well in this instance, it does not seem wise to expect the next crisis in drug development to be managed as well. Future crises will need better management and the challenge is to implement a system set up to respond globally and efficiently to a perceived drug-related hazard. In this regard, we discuss the roles of new tools the legislation has provided to the regulators and the value of an integrated expert assessment of all pre-approval data that may signal a potential safety issue in the postmarketing period. We also discuss the roles of other bodies such as the WHO Collaborating Centre for International Drug Monitoring, CIOMS and the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).
authors: Division of Cardiovascular and Renal Products, Center for Drug Evaluation and Research, US FDA, Silver Spring, MD, USA.
authors: Norman
authors: N
authors: Stockbridge
authors: Joel
authors: J
authors: Morganroth
authors: Rashmi R
authors: RR
authors: Shah
authors: Christine
authors: C
authors: Garnett
mesh_terms: D002317:Cardiovascular Agents / Q000009:adverse effects*; D017277:Drug Approval; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007391:International Cooperation; D008133:Long QT Syndrome / Q000139:chemically induced*; D055553:Prescription Drugs / Q000009:adverse effects*; D056737:Safety-Based Drug Withdrawals / Q000379:methods*; D016171:Torsades de Pointes / Q000139:chemically induced*
chemical_list: D002317:Cardiovascular Agents; D055553:Prescription Drugs