Publications by authors named "Florelle Bellet"

13 Publications

  • Page 1 of 1

Use of Social Media for Pharmacovigilance Activities: Key Findings and Recommendations from the Vigi4Med Project.

Drug Saf 2020 09;43(9):835-851

Laboratoire d'informatique médicale et d'ingénierie des Connaissances en e-santé, LIMICS, Sorbonne Université, Inserm, Université Paris 13, 75006, Paris, France.

The large-scale use of social media by the population has gained the attention of stakeholders and researchers in various fields. In the domain of pharmacovigilance, this new resource was initially considered as an opportunity to overcome underreporting and monitor the safety of drugs in real time in close connection with patients. Research is still required to overcome technical challenges related to data extraction, annotation, and filtering, and there is not yet a clear consensus concerning the systematic exploration and use of social media in pharmacovigilance. Although the literature has mainly considered signal detection, the potential value of social media to support other pharmacovigilance activities should also be explored. The objective of this paper is to present the main findings and subsequent recommendations from the French research project Vigi4Med, which evaluated the use of social media, mainly web forums, for pharmacovigilance activities. This project included an analysis of the existing literature, which contributed to the recommendations presented herein. The recommendations are categorized into three categories: ethical (related to privacy, confidentiality, and follow-up), qualitative (related to the quality of the information), and quantitative (related to statistical analysis). We argue that the progress in information technology and the societal need to consider patients' experiences should motivate future research on social media surveillance for the reinforcement of classical pharmacovigilance.
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http://dx.doi.org/10.1007/s40264-020-00951-2DOI Listing
September 2020

Liquid formulation of ifosfamide increased risk of encephalopathy: A case-control study in a pediatric population.

Therapie 2020 Sep - Oct;75(5):471-480. Epub 2019 Oct 28.

Department of medical pharmacology, CRPV, CHU de Clermont-Ferrand,63003 Clermont-Ferrand, France.

Background: Several clusters of encephalopathy occurred after the market change from Holoxan® (ifosfamide lyophilized powder) to Ifosfamide EG® (liquid formulation) and justified a formal survey in 2015. In June 2016, the regulatory authority decided to apply a precautionary measure in reducing the shelf life of Ifosfamide EG® at 7 months. One-year study from spontaneous reports lead to suspect a potential residual risk. Due to the many limitations associated with spontaneous notifications, we performed a multicentric observational study, aiming to better explore this pharmacovigilance signal.

Methods: We performed a case-control study in pediatric oncology Departments of 25 university hospitals between July 1st, 2016 and July 1st, 2018. All children (<18 y.o.) receiving liquid formulation or lyophilized powder formulation during the study period were included. Patients with at least one occurrence of encephalopathy were considered as cases. Logistic regression model was used to estimate the odds ratio of encephalopathy between exposure groups.

Results: During the study period, 52 cases and 495 controls were included. A residual over-risk of encephalopathy was associated with ifosfamide 7-month shelf-life liquid formulation compared to lyophilized powder (adjusted OR 1.91, 95% CI: 1.03-3.53).

Conclusions: Observed difference does not seem to be related to the pathology treated, the doses used, the co-medications, a meningeal localization and/or an irradiation of the central nervous system. This study confirms data from spontaneous reports that led to the precautionary measure for the liquid formulation. Even if the risk of encephalopathy seems reduced, our study suggests the persistence of a residual risk of encephalopathy associated with liquid formulation compared to the lyophilized powder.
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http://dx.doi.org/10.1016/j.therap.2019.08.001DOI Listing
October 2019

Pharmacology and social media: Potentials and biases of web forums for drug mention analysis-case study of France.

Health Informatics J 2020 06 30;26(2):1253-1272. Epub 2019 Sep 30.

Sorbonne Université and Université Paris 13, France; CHU University Hospital of Saint-Etienne, France.

The aim of this study is to analyze drug mentions in web forums to evaluate the utility of this data source for drug post-marketing studies. We automatically annotated over 60 million posts extracted from 21 French web forums. Drug mentions detected in this corpus were matched to drug names in a French drug database (Theriaque). Our analysis showed that a high proportion of the most frequent drug mentions in the selected web forums correspond to drugs that are usually prescribed to young women, such as combined oral contraceptives. The most mentioned drugs in our corpus correlated weakly to the most prescribed drugs in France but seemed to be influenced by events widely reported in traditional media. In this article, we conclude that web forums have high potential for post-marketing drug-related studies, such as pharmacovigilance, and observation of drug utilization. However, the bias related to forum selection and the corresponding population representativeness should always be taken into account.
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http://dx.doi.org/10.1177/1460458219865128DOI Listing
June 2020

Evaluating Twitter as a complementary data source for pharmacovigilance.

Expert Opin Drug Saf 2018 Aug 26;17(8):763-774. Epub 2018 Jul 26.

a Sorbonne Université , UPMC Université Paris 06, UMR_S 1142, LIMICS , Paris , France.

Background: Social media are currently considered as a potential complementary source of knowledge for drug safety surveillance. Our primary objective was to estimate the frequency of adverse drug reactions (ADRs) experienced by Twitter users. Our secondary objective was to determine whether tweets constitute a valuable and informative source of data for pharmacovigilance purposes, despite limitations on character number per tweet.

Research Design And Methods: We selected a list of 33 drugs subject to careful monitoring due to safety concern in France and Europe, and extracted tweets using the streaming API from 30 September 2014 to 5 April 2015. Two pharmacovigilance centers classified these tweets manually as potential ADR case reports.

Results: Among 10,534 tweets, 848 (8.05%) implied or mentioned an ADR without meeting the four FDA criteria required for reporting an ADR, and 289 (2.74%) tweets were classified as 'case reports.' Among them 20 (7.27%) tweets mentioned an unexpected ADR and 33 (11.42%) tweets mentioned a serious ADR.

Conclusions: With the use of dedicated tools, Twitter could become a complementary source of information for pharmacovigilance, despite a major limitation regarding causality assessment of ADRs in individual tweets, which may improve with the new limitation to 280 characters per tweet.
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http://dx.doi.org/10.1080/14740338.2018.1499724DOI Listing
August 2018

Descriptions of Adverse Drug Reactions Are Less Informative in Forums Than in the French Pharmacovigilance Database but Provide More Unexpected Reactions.

Front Pharmacol 2018 1;9:439. Epub 2018 May 1.

Sorbonne Université, INSERM, Université Paris 13, Laboratoire d'Informatique Médicale et d'Ingénierie des Connaissances en e-Santé, Paris, France.

Social media have drawn attention for their potential use in Pharmacovigilance. Recent work showed that it is possible to extract information concerning adverse drug reactions (ADRs) from posts in social media. The main objective of the Vigi4MED project was to evaluate the relevance and quality of the information shared by patients on web forums about drug safety and its potential utility for pharmacovigilance. After selecting websites of interest, we manually evaluated the relevance of the content of posts for pharmacovigilance related to six drugs (agomelatine, baclofen, duloxetine, exenatide, strontium ranelate, and tetrazepam). We compared forums to the French Pharmacovigilance Database (FPVD) to (1) evaluate whether they contained relevant information to characterize a pharmacovigilance case report (patient's age and sex; treatment indication, dose and duration; time-to-onset (TTO) and outcome of the ADR, and drug dechallenge and rechallenge) and (2) perform impact analysis (nature, seriousness, unexpectedness, and outcome of the ADR). The cases in the FPVD were significantly more informative than posts in forums for patient description (age, sex), treatment description (dose, duration, TTO), and outcome of the ADR, but the indication for the treatment was more often found in forums. Cases were more often serious in the FPVD than in forums (46% vs. 4%), but forums more often contained an unexpected ADR than the FPVD (24% vs. 17%). Moreover, 197 unexpected ADRs identified in forums were absent from the FPVD and the distribution of the MedDRA System Organ Classes (SOCs) was different between the two data sources. This study is the first to evaluate if patients' posts may qualify as potential and informative case reports that should be stored in a pharmacovigilance database in the same way as case reports submitted by health professionals. The posts were less informative (except for the indication) and focused on less serious ADRs than the FPVD cases, but more unexpected ADRs were presented in forums than in the FPVD and their SOCs were different. Thus, web forums should be considered as a secondary, but complementary source for pharmacovigilance.
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http://dx.doi.org/10.3389/fphar.2018.00439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938397PMC
May 2018

Bleeding risk under selective serotonin reuptake inhibitor (SSRI) antidepressants: A meta-analysis of observational studies.

Pharmacol Res 2017 04 10;118:19-32. Epub 2016 Aug 10.

INSERM, UMR 1059, SAINBIOSE, Dysfonction Vasculaire et Hémostase, Université Jean Monnet, F-42023, Saint-Etienne, France; Service de Médecine Vasculaire et Thérapeutique, CHU de Saint-Etienne, Hôpital Nord, F-42055, Saint-Etienne, France; INSERM, CIC1408, F-42055, Saint-Etienne, France. Electronic address:

Selective serotonin reuptake inhibitors (SSRIs) have been reported to be potentially associated with an increased risk of bleeding. A meta-analysis of observational studies was conducted to quantify this risk. Case-control and cohort studies investigating bleeding risk under SSRI therapy were retrieved by searching the Medline, Pascal, Google Scholar and Scopus databases. Case-control studies were included if they reported bleeding incidents with and without the use of SSRIs and cohort studies were included if they reported the rate of bleeds among SSRI users and non-users. The main outcome was severe bleeding, whatever the site. Only data concerning SSRI belonging to the ATC class N06AB were used. For both case-control and cohort studies, we recorded the adjusted effect estimates and their 95% confidence intervals (CI). Pooled adjusted odds ratio (OR) estimates were computed for case-control and cohort studies using an inverse-variance model. Meta-analysis of the adjusted ORs of 42 observational studies showed a significant association between SSRI use and the risk of bleeding [OR 1.41 (95% CI 1.27-1.57), random effect model, p<0.0001]. The association was found for the 31 case-control studies (1,255,073 patients), with an increased risk of 41% of bleeding [OR 1.41 (95% CI 1.25-1.60)], as well as for the 11 cohort studies including 187,956 patients [OR 1.36 (95% CI 1.12-1.64)]. Subgroup analyses showed that the association remained constant whatever the characteristics of studies. This meta-analysis shows an increased risk of bleeding of at least 36% (from 12% to 64%) based on the high-level of observational studies with SSRIs use.
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http://dx.doi.org/10.1016/j.phrs.2016.08.017DOI Listing
April 2017

Direct oral anticoagulants: Current indications and unmet needs in the treatment of venous thromboembolism.

Pharmacol Res 2017 04 24;118:33-42. Epub 2016 Jun 24.

INSERM, U1059, Dysfonction Vasculaire et Hémostase, Saint-Etienne, France; CHU Saint-Etienne, Unité de Recherche Clinique et d'Innovation Pharmacologique, Saint-Etienne, France. Electronic address:

The treatment of acute venous thromboembolism (VTE) is being completely modified with the development of direct oral anticoagulants (DOACs). Rivaroxaban, apixaban and edoxaban directly inhibit factor Xa, whereas dabigatran inhibits factor IIa. All these drugs are proposed orally, and share pharmacological similarities: fixed doses without any therapeutic drug monitoring, key role of the transporter proteins P-glycoprotein for all of them and metabolism mediated by CYP3A4 for the anti-Xa, short half-life with variable rate of renal elimination. More than 25 000 patients with acute VTE were included in phase-III studies. Rivaroxaban and apixaban challenged all the conventional therapy (parenteral heparins followed by anti-vitamin K antagonists) whereas edoxaban and dabigatran challenged only anti-vitamin K antagonists. All the DOACs met the non-inferiority efficacy endpoint (recurrent VTE during treatment), whereas the large non-inferiority margin was debated for dabigatran. However, they were associated with better safety and a decreased risk of major bleeding. According to indirect comparisons, there were no statistically significant differences between DOACs in terms of efficacy but some differences are not excluded in term of safety. Although DOACs allow for simplification of treatment in the majority of patients with acute VTE, their risk/benefit ratio is questioned in elderly patients, patients with mild-to-severe renal impairment, and in some clinical subgroups such as cancer or chronic thromboembolic pulmonary hypertension. Validated reversal strategies (potentially based on laboratory monitoring) are expected for patients with major bleeding, overdose or with a need for surgery.
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http://dx.doi.org/10.1016/j.phrs.2016.06.023DOI Listing
April 2017

Adverse Drug Reaction Identification and Extraction in Social Media: A Scoping Review.

J Med Internet Res 2015 Jul 10;17(7):e171. Epub 2015 Jul 10.

Université Paris 13, Sorbonne Paris Cité, Laboratoire d'Informatique Médicale et d'Ingénieurie des Connaissances en e-Santé (LIMICS), (Unité Mixte de Recherche en Santé, UMR_S 1142), F-93430, Villetaneuse, France, Sorbonne Universités, University of Pierre and Marie Curie (UPMC) Université Paris 06, Unité Mixte de Recherche en Santé (UMR_S) 1142, Laboratoire d'Informatique Médicale et d'Ingénieurie des Connaissances en e-Santé (LIMICS), F-75006, Institut National de la Santé et de la Recherche Médicale (INSERM), U1142, Laboratoire d'Informatique Médicale et d'Ingénieurie des Connaissances en e-Santé (LIMICS), F-75006, Paris, France.

Background: The underreporting of adverse drug reactions (ADRs) through traditional reporting channels is a limitation in the efficiency of the current pharmacovigilance system. Patients' experiences with drugs that they report on social media represent a new source of data that may have some value in postmarketing safety surveillance.

Objective: A scoping review was undertaken to explore the breadth of evidence about the use of social media as a new source of knowledge for pharmacovigilance.

Methods: Daubt et al's recommendations for scoping reviews were followed. The research questions were as follows: How can social media be used as a data source for postmarketing drug surveillance? What are the available methods for extracting data? What are the different ways to use these data? We queried PubMed, Embase, and Google Scholar to extract relevant articles that were published before June 2014 and with no lower date limit. Two pairs of reviewers independently screened the selected studies and proposed two themes of review: manual ADR identification (theme 1) and automated ADR extraction from social media (theme 2). Descriptive characteristics were collected from the publications to create a database for themes 1 and 2.

Results: Of the 1032 citations from PubMed and Embase, 11 were relevant to the research question. An additional 13 citations were added after further research on the Internet and in reference lists. Themes 1 and 2 explored 11 and 13 articles, respectively. Ways of approaching the use of social media as a pharmacovigilance data source were identified.

Conclusions: This scoping review noted multiple methods for identifying target data, extracting them, and evaluating the quality of medical information from social media. It also showed some remaining gaps in the field. Studies related to the identification theme usually failed to accurately assess the completeness, quality, and reliability of the data that were analyzed from social media. Regarding extraction, no study proposed a generic approach to easily adding a new site or data source. Additional studies are required to precisely determine the role of social media in the pharmacovigilance system.
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http://dx.doi.org/10.2196/jmir.4304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4526988PMC
July 2015

Exposure to aripiprazole during embryogenesis: a prospective multicenter cohort study.

Pharmacoepidemiol Drug Saf 2015 Apr 12;24(4):368-80. Epub 2015 Feb 12.

Centre Régional de Pharmacovigilance, Centre Hospitalo-Universitaire, Saint-Etienne, France.

Purpose: The main purpose of this study was to evaluate the risk of major malformations after aripiprazole exposure during the embryonic period. The secondary purposes were to assess the risk of miscarriage, prematurity, fetal growth retardation and maternal complications and to describe possible neonatal adverse effects.

Methods: We conducted a cohort study using data prospectively collected by the French Pharmacovigilance Centres participating to the Terappel program and the Centre de Référence sur les Agents Tératogènes between 2004 and 2011. The exposed group consisted of pregnant women exposed to aripiprazole during embryogenesis, and the unexposed group consisted of pregnant women without exposure or exposed to non-teratogenic agents. Two unexposed patients, matched for age and gestational age at call, were randomly selected for each exposed patient.

Results: Eighty-six patients were included in the exposed group and 172 in the unexposed group. Exposure to aripiprazole was not significantly associated with an increased rate of major malformations (OR 2.30, 95%CI 0.32-16.7) or miscarriage (1.66, 0.63-4.38) or gestational diabetes (1.15, 0.33-4.04) compared to non-exposure. The study revealed significantly increased rates of prematurity (OR 2.57, 95%CI 1.06-6.27) and fetal growth retardation (2.97, 1.23-7.16) in exposed newborns, difficult to interpret because of the short duration of maternal exposure. Two cases of neonatal complications were reported among the 19 newborns exposed to aripiprazole near delivery.

Conclusion: This study failed to demonstrate a significant association between aripiprazole exposure during the embryonic period and major malformations. More powerful prospective studies are required to clarify the reproductive safety profile of aripiprazole.
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http://dx.doi.org/10.1002/pds.3749DOI Listing
April 2015

[Not Available].

Therapie 2014 Nov-Dec;69(6):483-90

Centre de pharmacovigilance, Centre hospitalier universitaire de Saint-Étienne, Saint-Étienne - Hôpital Nord, France.

Aim: To evaluate the value of research in the case-mix database to identify cases of drug-related anaphylactic or anaphylactoid shock.

Methods: Hospital stays of patients discharged from the University Hospital of Saint-Étienne between July 1st 2009 and June 30th 2012. Five codes from the international classification of diseases were selected: T88.6, T88.2, J39.3, T80.5 and T78.2.

Results: Among 89 cases identified by the programme for medicalization of information system (programme de médicalisation des systèmes d'information, PMSI), 40 were selected (45%). Of these, 16 cases were spontaneously reported by physicians. The unspecific code "anaphylactic shock unspecified (T78.2)" was coded for 57.5% of cases.

Conclusion: The study confirms the interest of the PMSI as a tool for health monitoring, in addition to spontaneous reporting. Nevertheless, coding with insufficient precision about the causal role of the drug, requires a return to the medical record and so an important time consuming process.
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http://dx.doi.org/10.2515/therapie/2014057DOI Listing
July 2016

[Drug-related anaphylactic shocks: under-reporting and PMSI].

Therapie 2014 Nov-Dec;69(6):483-90. Epub 2014 Oct 1.

Centre de pharmacovigilance, Centre hospitalier universitaire de Saint-Étienne, Saint-Étienne - Hôpital Nord, France.

Aim: To evaluate the value of research in the case-mix database to identify cases of drug-related anaphylactic or anaphylactoid shock.

Methods: Hospital stays of patients discharged from the University Hospital of Saint-Étienne between July 1st 2009 and June 30th 2012. Five codes from the international classification of diseases were selected: T88.6, T88.2, J39.3, T80.5 and T78.2.

Results: Among 89 cases identified by the programme for medicalization of information system (programme de médicalisation des systèmes d'information, PMSI), 40 were selected (45%). Of these, 16 cases were spontaneously reported by physicians. The unspecific code "anaphylactic shock unspecified (T78.2)" was coded for 57.5% of cases.

Conclusion: The study confirms the interest of the PMSI as a tool for health monitoring, in addition to spontaneous reporting. Nevertheless, coding with insufficient precision about the causal role of the drug, requires a return to the medical record and so an important time consuming process.
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http://dx.doi.org/10.2515/therapie/2014057DOI Listing
February 2015

Efficacy of baclofen on abstinence and craving in alcohol-dependent patients: a meta-analysis of randomized controlled trials.

Therapie 2014 Sep-Oct;69(5):427-35. Epub 2014 Sep 18.

Centre régional de Pharmacovigilance de la Loire, Centre hospitalier et universitaire de Saint-Étienne, Saint-Étienne, France - EA3065, Groupe de recherche sur la thrombose, Université Jean-Monnet, Saint-Étienne, France.

Purpose: We conducted a meta-analysis in order to estimate the efficacy of baclofen on the maintenance of abstinence and the decrease of craving in alcohol-dependent patients.

Methods: All randomized controlled clinical trials assessing baclofen for at least four weeks' treatment duration versus placebo or other comparators were included. The primary outcome measure was the percentage of patients who had not consumed alcohol at the end of the treatment. Measures of cumulative abstinence and indexes of craving were also assessed.

Results: Compared to placebo, baclofen was associated with a significant increase of 179% in the percentage of abstinent patients at the end of the trial, without heterogeneity. For secondary outcome measures, based on a random-effect model, no significant effect of baclofen was observed compared to placebo.

Conclusions: Our meta-analysis brings weak support towards an efficacy of low dosages of baclofen on the maintenance of abstinence in alcohol-dependent patients.
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http://dx.doi.org/10.2515/therapie/2014038DOI Listing
February 2015