The Measures of French Regulatory Agency for Clinical Trials Conduction After the Rennes Disaster

Abstract

To show how French system reacted to the so-called “Rennes Disaster”, in which six healthy volunteers, after a fatty acid amide hydrolase inhibitor intake, presented serious brain damage and one died subsequently to these lesions. The aim of this communication was to illustrate the requirements of French Ministry of Health after the “Rennes Disaster”, and how the safety and vigilance units of academic sponsors implemented these new requirements in their routine activity. The key points of changes in French regulatory requirements were summarized. Thereafter, a focus on the actions of the Revise (REflections on VIgilance and SafEty of Clinical trials) Network was presented. The Revise Network was created on 2007, and it now federates around fifty safety units of academic sponsors. From the beginning, the majority of them were supported by a pharmacology department in the context of French regional centres of pharmacovigilance. After the Rennes Disaster, the ministry of health imposed that in all study on drugs performed on healthy subjects, every serious adverse reaction leading to hospitalisation must be considered as an emerging safety issue and reported immediately to the French Drug Safety Agency (Agence Nationale de la securité du Médicament, ANSM). The study must be interrupted immediately and, to restart with the inclusions, the sponsor must bring proof its harmlessness to ANSM. Moreover, all healthy subjects must be informed and give a new consent before any new administration. Later on, the Jardé law considered all serious adverse events observed on healthy volunteers as a safety issue and must be reported immediately to ANSM. In any other clinical trial phases, life-threatening or fatal SUSARs (suspected unexpected adverse drug reaction) must be reported without any delay to ANSM. The extreme short time to assess serious adverse events before the transmission, imposed to reinforce the organisation of vigilance units for their management. The Revise Network proposed 30 guidelines to harmonies the procedures, such as a guideline for a safety management plan tailored to the evaluation of benefit risk assessment based on clinical pharmacology expertise. The French authorities and the vigilance units promptly reacted to the Rennes Disaster. The Revise Network, university hospital directorates and the institutional pharmacology units are working together to help in better preventing and managing the safety of people included in clinical trials.