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Introduction: Qualitative approaches based on drug causality assessment estimate the causal link between a drug and the occurrence of an adverse event from individual case safety reports. Quantitative approaches based on disproportionality analyses were developed subsequently to allow automated statistical signal detection from pharmacovigilance databases. This study assessed the potential value of causality assessment for automated safety signal detection. Methods: All drug–serious adverse event pairs with a positive rechallenge and a semiology suggestive of drug causality were identified in the French pharmacovigilance database (BNPV) from 2011 to 2017. The results were compared with those obtained from automated disproportionality analyses of the BNPV/World Health Organization (WHO) VigiBase®, complemented by the list of signals validated by the WHO-UMC (Uppsala Monitoring Centre). Summary of Product Characteristics (SmPCs), Martindale®, Meyler's® and MedLINE® were used as other sources of information for the purpose of comparison. Results: Of the 155 pairs of interest, 115 (74.2%) were also identified by another source of information. Since the individual case reporting in the BNPV, 23 (14.8%) of the adverse events (AEs) have been added to the SmPC, seven of which were not identified by disproportionality. Finally, 40 pairs were not identified by any other source of information, 13 of which were considered as potential new safety signals after analysis of case reports by pharmacovigilance experts. The signals identified by causality assessment involved antineoplastic and immunomodulatory drugs especially, in comparison with signals identified by WHO-UMC or by disproportionality within the BNPV. Conclusion: The approach therefore appears useful as an additional tool for safety signal detection, especially for antineoplastic and immunomodulating agents. [ABSTRACT FROM AUTHOR]

Background: Perioperative anaphylaxis mainly involves neuromuscular blocking agents (NMBAs) with an IgE‐mediated mechanism. In France, this life‐threatening condition is reported by anesthetists and allergologists, and two safety alerts concerning suxamethonium were raised in 2011 and 2012. This led to start a national survey over the 2000‐2012 period which objectives were to provide a descriptive analysis, to estimate incidence rates, and to analyze the trends over this period. Methods: The French pharmacovigilance database was retrospectively queried for all the available NMBAs. Anaphylaxis cases with elevated tryptase and positive skin tests were qualified as "confirmed cases." Subgroup analysis compared atracurium and cisatracurium vs suxamethonium and rocuronium. Results: A total of 680 confirmed cases and 944 nonconfirmed cases were identified. Suxamethonium was the most implied NMBA (64%). Incidence rates (according to sales data) of suxamethonium and rocuronium were, respectively, 10‐ and 13‐folds higher than those of the others NMBAs, regardless the confirmed/nonconfirmed status. Cisatracurium incidence rates remained stable over the period, while suxamethonium and atracurium increased and rocuronium first decreased but re‐increased after 2006. Male patients were more frequent in the subgroup "atracurium‐cisatracurium" (P = .019), whereas obesity and emergency setting were more frequent in the subgroup "rocuronium‐suxamethonium." Shared characteristics were the poorly documented previous exposure to NMBA(s) and an insufficient adherence of patients to perform skin tests, showing the need to improve this procedure. Conclusion: Suxamethonium and rocuronium are markedly more involved in perioperative anaphylaxis than the other available NMBAs. Patients should be more informed about their perioperative anaphylaxis and its consequences. Perioperative anaphylaxis mainly involves neuromuscular blocking agents (NMBAs), and over the 2000‐2012 period, suxamethonium and rocuronium each had anaphylaxis incidence rates more than tenfold higher than atracurium and cisatracurium. Over this 13‐year period, the incidence rate of NMBA anaphylaxis showed a significant increase for suxamethonium and atracurium, whereas it remained stable for cisatracurium. Rocuronium displayed a 2‐period curve with a significant increase from 2005. Patients need to be more aware about the importance of allergological skin tests for ensuring safe further anesthetic procedures. [ABSTRACT FROM AUTHOR]

A tripartite group, entitled « CRI » (for Cercle de réflexion sur l'imputabilité), involving French pharmacovigilance staff from the French network of the Regional centers of pharmacovigilance, from pharmaceutical companies, and from French Health Authorities (Agence française de sécurité sanitaire des produits de santé) has worked to update the French drug reaction assessment method. Following assessment of strengths and weaknesses of the previous method, several points for improvement are proposed: a more precise wording and a more discriminating scale for some of the chronological and semiological criteria, a wider distribution of the intrinsic score from 5 to 7 levels, a new bibliographic scale for differentiating expected and unexpected adverse drug reactions, and a new informativness scale. This updated method would lead to a more relevant assessment of relationship between a drug and the occurrence of an adverse reaction. Furthermore, this method is a teaching tool to assess the level of relationship between a drug and the occurrence of an adverse reaction., (© 2011 Société Française de Pharmacologie et de Thérapeutique.)

A tripartite group, entitled « CRI » (for Cercle de réflexion sur l'imputabilité), involving French pharmacovigilance staff from the French network of the Regional centers of pharmacovigilance, from pharmaceutical companies, and from French Health Authorities (Agence française de sécurité sanitaire des produits de santé) has worked to update the French drug reaction assessment method. Following assessment of strengths and weaknesses of the previous method, several points for improvement are proposed : a more precise wording and a more discriminating scale for some of the chronological and semiological criteria, a wider distribution of the intrinsic score from 5 to 7 levels, a new bibliographic scale for differentiating expected and unexpected adverse drug reactions, and a new informativness scale. This updated method would lead to a more relevant assessment of relationship between a drug and the occurrence of an adverse reaction. Furthermore, this method is a teaching tool to assess the level of relationship between a drug and the occurrence of an adverse reaction., (Copyright © 2011 Société Française de Pharmacologie et de Thérapeutique. Publié par Elsevier Masson SAS.)