The French pharmacovigilance surveys: A French distinctiveness, a real input.

INTRODUCTION: According to French guidelines on good pharmacovigilance practices, a pharmacovigilance survey is an assessment of the available drug safety data. It is requested by the French national agency for medicines and health products safety (ANSM). The objective is to validate a signal, to characterize it, or to provide strengthened monitoring of a drug. MATERIAL AND METHODS: All the available data were retrieved by ANSM/Regional Pharmacovigilance Centers (RPC) and assessed by a nominate RPC which provides a report for discussion during the monthly Committee between ANSM and the Regional Pharmacovigilance Network (RPN). A descriptive analysis of the minutes available on the ANSM website between 2016 and 2018 has been done: objective, data sources, duration of the survey, number of suspected adverse drug reactions, nature of the drugs and of the signals and recommendations for actions. RESULTS: Between 2016 and 2018, a total of 115 surveys were discussed concerning 135 drugs, mainly from the nervous system according to the anatomic therapeutic chemical classification (n=31, 27%). They involved a whole pharmacological class for 18 ones. The main objective of the 115 surveys was to provide a strenghtened monitoring for some drugs (72%) or to validate one or more than one signal (28%). Result from surveys allowed to detect one or several new potential safety signals in 63 ones (55%), an off-label-use in 12 (10%) or to characterize some others signals in all the studies. The Committee recommended one or several actions by survey: 67 prolongations (58%) of the survey and regulatory or investigatory actions which included 43 European actions (37%), 37 label changes (32%), 30 national communications (26%) and 29 additional monitoring (25%). DISCUSSION/CONCLUSION: The current process allows a collegiate, clinical and pharmacological discussion with integration of the regulatory framework. A significant number of new signals are detected and/or validated. This efficient tool which is unique in Europe and is allowed by the decentralized pharmacovigilance which leads to a great reactivity of decision-making. It has to be reassessed and to be adapted continuously to the new challenges of the growing multiplication of signals.

Interest of pharmacoepidemiology in pharmacovigilance: Post-authorization safety studies in regulatory pharmacovigilance activity.

During the past few decades, it has been stated that a paradigm shift has occurred in the assessment and management of patient related drug safety. Some of these changes have resulted in a significant increase in the importance of pharmacoepidemiology and its use in pharmacovigilance. For European member states, the Pharmacovigilance Risk Assessment Committee (PRAC) is responsible for assessing the protocols and results of imposed and non-imposed post-authorization safety studies (PASS). Between 2013 and 2017, the total number of PASS during this 5-years period of the different products, including protocols and results, was 1062. The number of protocols of PASS is increasing over time, except in 2017 where a 25% decrease has been observed. Whereas, PASS results steadily increased over the 5years period. Between 2014 and 2017, about 29% (n=137) of PRAC reviewed protocols were imposed. The number of imposed PASS was almost constant over time with a mean of 34.3±7.6 imposed protocols per year and 3.5±1.74 imposed results per year. The need for the implementation of PASS for pharmacovigilance regulatory activities is increasing. Nevertheless, conducting such studies remains difficult.

Antipsychotics-induced ischaemic colitis and gastrointestinal necrosis: a review of the French pharmacovigilance database.

PURPOSE: First- and second-generation antipsychotics commonly cause mild gastrointestinal hypomotility. Intestinal necrosis may be a consequence of such gastrointestinal perturbations. MATERIAL AND METHODS: We reviewed all the observations of ischaemic colitis and gastrointestinal necrosis notified to the French Pharmacovigilance database (FPD) between 1997 and the end of 2006. RESULTS: Thirty-eight cases of ischaemic colitis and gastrointestinal necrosis associated with antipsychotics were analysed. The average age of the patients was 42.7 +/- 14.7 years (15-77 years). The digestive complication was an intestinal necrosis in 27 cases, an ischaemic colitis in 10 cases (with perforation in three cases), and one perforation. Surgical procedure (partial or total resection of the colon and/or small intestine) was performed in 24 patients. Six patients died despite surgery. Among the whole population, the outcome was fatal in 14 patients, 13 patients recovered with sequelae, six patients fully recovered, and the outcome remained unknown in five cases.In 55.2% of the cases, the patients were treated with more than one antipsychotic medication. The most frequently involved antipsychotics were: clozapine, levomepromazine, cyamemazine, haloperidol. Associated antimuscarinic drugs (excluding antipsychotics) were found in 68.4% of patients. DISCUSSION/CONCLUSION: Intestinal necrosis associated with antipsychotics is very rare; however mortality is high, with a rapid worsening of patients towards septic shock in spite of mild clinical symptoms. It is therefore essential to monitor the patients receiving antipsychotics especially when they are prescribed concomitant medications. The occurrence of non-specific clinical symptoms such as abdominal pain associated with vomiting and/or diarrhea should draw attention.