Results of the 2017 inspection campaign of French phase I/II research sites in Île-de-France following the BIA 10-2474 accident: Medical vs. regulatory relevance

Summary Aims Following the serious adverse events that occurred in January 2016 during the BIA 10-2474 First-in-Human study, the French Ministry of Health asked the Regional Health Agencies to inspect operations at all research sites conducting phase I/II clinical trials of experimental drugs. The aim of this study was to assess the medical relevance of the inspections made in Ile-de-France (Paris region) in 2017. Methods All 30 sites of Ile-de-France region fully authorized to perform phase I/II trials were inspected by a public health physician and a public health pharmacist. Their reported list of observations was submitted to three physicians with longstanding experience of early pharmacology studies performed in academic or private research facilities. These physicians were asked to adjudicate each observation according to their perceived medical importance regarding safety. Adjudications were first performed separately and disagreements were later settled during a final adjudication meeting. Results At least one disagreement occurred initially among the 3 adjudicators for 84 of the 120 observations (70%) reported by the inspectors. Following reconciliation, the 3 physicians agreed that 20% of the observations were likely to have potentially serious medical consequences. These observations mainly concerned the management of emergencies and of serious adverse events and the continuity of care. Conclusions Maintenance of on-site inspections periodically carried out by regulatory authorities granting authorisations to perform phase I/II trials are justified. However, the medical relevance of these inspections can be improved with more emphasis on factors affecting the safety of research participants than on administrative or purely regulatory issues.