Lessons Learnt from 5 Cases of Neurological Adverse Events and Death Occurring in the Clinical Trial of BIA 10-2474

In January 2016, a healthy subject in the Phase Ⅰ clinical trial of BIA 10-2474 in France experienced brain death after administration of the studied medicine. In order to explore the cause of this event and systematically mitigate the risk of early-phase clinical trials, this article sorted out the potential reasons in terms of the mechanism of drug effect, preclinical findings, design and execution of the clinical study based on the report written by the Temporary Specialist Scientific Committee involved in the survey of the BIA 10-2474 study. The lessons learnt from this tragedy may include:(1)the decision on clinical development should be made carefully according to available research data and relevant information obtained from similar drugs, so as to improve the rate of success and avoid unnecessary risks; (2)the trial design should consider safety findings and pharmacody-namic properties of the drug in pre-clinical studies, as well as the scientific objectives of the study; (3)in early-stage clinical trials of novel drugs, investigators should be fully aware of the potential risks, even small signals should be noted. Whenever there is an emerging event, it is recommended to perform a comprehensive analysis on the event and then treat it conservatively.