This proposed study aims to assess the risk of abnormal heart rhythms and deaths associated with the use of drugs within the Comprehensive in Vitro Proarrhythmia Assay (CiPA) initiative. The CiPA initiative was established by international government agencies, academia and pharmaceutical companies to develop a new standard for assessing the risk of abnormal heart rhythms with new drugs being marketed around the world.
An international panel of experts categorized 28 different CiPA drugs into categories based on the drug's risk for abnormal heart rhythms: low, medium or high. However, this risk categorization process was mainly based on expert opinion and these drugs have not been assessed using large scale patient data for the drug's actual risk of abnormal heart rhythms. Furthermore, the abnormal heart rhythms caused by certain drugs are more common in women and the proposed CiPA paradigm does not initially take gender into consideration. The proposed research would help to identify if the drugs on the CiPA list are appropriately divided in their respective risk categories. In addition, we will assess the appropriate categorization of CiPA drugs in women and men, separately.
This proposed study aims to assess the incidence of cardiac arrhythmia and cardiac mortality in patients using different Comprehensive in Vitro Proarrhythmia Assay (CiPA) drugs that were non-empirically identified as having varying risk of Torsade de Pointes (Torsade), a potentially fatal cardiac arrhythmia. The CiPA initiative was established by international government agencies, academia and pharmaceutical companies to develop a new paradigm for assessing proarrhythmic risk of drugs (in addition to only QT prolongation), building on the emergence of new technologies and an expanded understanding of the mechanisms of arrhythmia.
The different drugs in the CiPA risk categories are based on expert opinion from an international panel and have not been thoroughly assessed for actual arrhythmic risk. There are 28 drugs within different Torsade risk categories (low, medium, and high) on the list for validation of the new CiPA paradigm (Appendix). The proposed research would help to descriptively quantify real-world arrhythmia risk for the different categories within CiPA and use this information to determine if the 28 drugs are accurately categorized in terms of their risk categories under CiPA. In addition, since Torsade is more common in women and the proposed CiPA paradigm does not initially take sex into consideration, we will assess the appropriate categorization of CiPA drugs in women and men, separately.
Torsade de Pointes
- Cardiac Arrest
- Abnormal/prolonged QT
- Arrhythmia
- Sudden cardiac death
- Ventricular abnormalities
- Tachycardia
- Mortality
Robbert Zusterzeel - Chief Investigator - Food and Drug Administration - FDA
Robbert Zusterzeel - Corresponding Applicant - Food and Drug Administration - FDA
Veronica Sansing-Foster - Collaborator - Food and Drug Administration - FDA
Xie Diqiong - Collaborator - Food and Drug Administration - FDA
HES Accident and Emergency;HES Admitted Patient Care;HES Diagnostic Imaging Dataset;HES Outpatient;ONS Death Registration Data