Serious adverse drug events related to non-investigational drugs in academic clinical trials: another source of safety data for risk assessment?
Sponsors of clinical trials have to analyze serious adverse events (SAEs). Both sponsors and investigators determine the relationship between the investigational medicinal product, the investigational device or procedure and SAEs. SAEs related to another cause, such as a non-investigational medicinal product (NIMP), do not have clear pharmacovigilance reporting requirements. The aim of this study was to evaluate the amount and the nature of NIMP-related SAEs recorded by three French academic sponsors and to propose pharmacovigilance requirements for these cases.



This was a retrospective descriptive study including all cases of NIMP-related SAEs occurring in clinical trials and reported to three academic sponsors between January 2009 and October 2014.



Among 5870 cases of SAEs, 300 (5%) were related to a NIMP in 50 clinical trials. Involved NIMPs were mainly antithrombotics, cytostatics and immunosuppressants. Some of these drugs were currently followed by a risk management plan (e.g. rivoxaban). The most frequent NIMP-related SAEs were neurological, gastrointestinal and infectious disorders. Seven NIMP-related SAEs were known as 'rare' or 'very rare' and two were 'unlabelled'.



As far as we know, this is the first study to focus about NIMP-related SAEs occurring in clinical trials. This work highlights the potential high quality source of safety data via NIMP-related SAE collection. Globally, we propose that NIMP-related SAEs occurring in clinical trials should systematically be notified to the pharmacovigilance system of the concerned country. Clearer procedures of interactions between safety units of academic sponsors and pharmacovigilance systems are needed to allow an effective recording of NIMP-related SAEs.
Service de Pharmacologie médicale et clinique, Centre Midi-Pyrénées de Pharmacovigilance, d'informations sur le médicament et de Pharmacoépidémiologie du CHU de Toulouse, Faculté de Médecine, 37 allées Jules Guesde, 31000, TOULOUSE. pascale.olivier@univ-tlse3.fr.|Vigilance des essais cliniques, Direction de la Recherche et de l'Innovation du CHU de Toulouse, 2 rue Viguerie, 31059, Toulouse Cedex. pascale.olivier@univ-tlse3.fr.
Pascale
P
Olivier
Valerie MARTY and Francesco SALVO Direction de la Recherche Clinique et de l'Innovation Unité de sécurité et de vigilance - Département promotion interne, Direction Générale des hôpitaux de Bordeaux, 12 rue Dubernat, 33 404, Talence cedex.
Anne
A
Gimbert
Vigilance des essais cliniques, Direction de la Recherche et de l'Innovation du CHU de Toulouse, 2 rue Viguerie, 31059, Toulouse Cedex.
Anne-Laurène
AL
Colin
Valerie MARTY and Francesco SALVO Direction de la Recherche Clinique et de l'Innovation Unité de sécurité et de vigilance - Département promotion interne, Direction Générale des hôpitaux de Bordeaux, 12 rue Dubernat, 33 404, Talence cedex.|INSERM, UMR1219, Bordeaux Population Health Research Center, Pharmacoepidemiology team, University of Bordeaux, Bordeaux.
Francesco
F
Salvo
Centre Régional de Pharmacovigilance de Lorraine, Laboratoire de Pharmacologie Clinique et de Toxicologie Hôpital Central, 29 avenue du Maréchal de Lattre de Tassigny CO 60034, 54035, Nancy cedex.
Madlyne
M
Becker
Valerie MARTY and Francesco SALVO Direction de la Recherche Clinique et de l'Innovation Unité de sécurité et de vigilance - Département promotion interne, Direction Générale des hôpitaux de Bordeaux, 12 rue Dubernat, 33 404, Talence cedex.
Valérie
V
Marty
Service de Pharmacologie médicale et clinique, Centre Midi-Pyrénées de Pharmacovigilance, d'informations sur le médicament et de Pharmacoépidémiologie du CHU de Toulouse, Faculté de Médecine, 37 allées Jules Guesde, 31000, TOULOUSE.
Jean-Louis
JL
Montastruc
Centre Régional de Pharmacovigilance de Lorraine, Laboratoire de Pharmacologie Clinique et de Toxicologie Hôpital Central, 29 avenue du Maréchal de Lattre de Tassigny CO 60034, 54035, Nancy cedex.
Nadine
N
Petitpain
D002986:Clinical Trials as Topic; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology*; D005602:France / Q000453:epidemiology; D006801:Humans; D060735:Pharmacovigilance; D012189:Retrospective Studies; D018570:Risk Assessment / Q000379:methods*
adverse reaction; non-investigational medicinal product; pharmacovigilance