Marie-Noëlle Beyens

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

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.

Serious Adverse Reactions of Bupropion for Smoking Cessation : Analysis of the French Pharmacovigilance Database from 2001 to 2004

AbstractBackground: Bupropion was the first alternative to nicotine replacement therapy in the pharmacological treatment for smoking cessation. Its safety profile has been monitored in France via spontaneous reporting. Objective: To describe all serious adverse reactions (SARs) reported in France since the marketing authorization for bupropion in September 2001, and to analyse risk factors for these SARs. Design: We collected all spontaneous reports of adverse reactions to bupropion received by all French Regional Pharmacovigilance Centres and by GlaxoSmith-Kline, the manufacturer of bupropion, during the first 3 years of marketing of this agent. We identified the characteristics of the population to whom bupropion was prescribed from the Thales database, which contains information obtained from a representative sample of general practitioners in France. We then compared the population with SARs with the population prescribed the drug (exposed population) to identify possible risk factors such as sex, age and daily dose for the most frequent SARs. Results: Bupropion was prescribed to 698 000 patients during the first 3 years of marketing in France. In these patients, 1682 cases of adverse reactions were reported; 28% of these involved SARs, mainly cutaneous or allergic reactions (31.2%), including angioedema and serum sickness-like reactions. Serious neurological reactions were frequent (22.5%), mostly comprising seizures; however, questioning revealed that almost half of these patients had a history of seizures or other risk factors. Of the serious neuropsychiatric adverse events reported (17.3%), suicide attempts/suicides were a cause for concern, although risk factors (history of depression, suicide attempts, etc.) were described for 66% of patients experiencing these events. Patients reporting angioedema and serum sickness-like reactions, and those involved in suicide attempts/suicides, were significantly younger than the exposed population. A dose-dependent effect was also apparent for angioedema and for seizures. Cardiovascular SARs, such as ischaemic heart disease (10.1%) or sudden death (2.3%), were very often associated with preexisting coronary artery disease induced by smoking. All these SARs occurred within a median of 12–14 days after drug initiation. Conclusion: To ensure safer use of bupropion, health professionals must respect the strict contraindications and warnings about use of this drug in patients with a history of seizures. Seizures, angioedema and serum sickness-like reactions were the most frequently reported SARs to bupropion treatment in our study. Moreover, younger people appeared to be more at risk for cutaneous SARs generally, and younger women for angioedema in particular, perhaps because of weight-related differences in pharmacokinetics. A dose-dependent effect for angioedema and the results of skin tests were suggestive of a histamine liberation mechanism. Our analysis showed that taking more notice of the contraindications to use of bupropion could have prevented half the seizures reported to the database. The sex and age characteristics of patients with ischaemic heart disease and suicide attempts in the study population were similar to those of the French population as a whole. Whether bupropion is associated with an increase in these potential adverse effects of therapy can be determined only by epidemiological studies that take into account specific risk factors in the smoking population. Finally, the median time to onset of the SARs identified in this study suggests that prescribers should monitor patients exposed to bupropion more carefully during the first 2 weeks of treatment.

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

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.

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

Graphical abstract Figure. No caption available. &NA; 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.

Complications of BCG vaccine SSI® recent story and risk management plan: the French experience.

As of January 2006, the BCG vaccine SSI® became the only BCG vaccine available for tuberculosis vaccination in France. The use of this vaccine led to significant changes in vaccination technique which were accompanied by a rapid increase in the number of adverse reactions (ADRs) reported. A national pharmacovigilance follow‐up began in February 2006, and a risk management plan (RMP) was put in place in April 2006, made of three phases (carried out in June 2006, July 2006 and September 2006) with risk minimisation measures.

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

Background: 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. Methods: 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). Results: 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. Discussion: 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.

Nicorandil and cutaneous ulcerations, their misdiagnosis and consequences: Illustration by five cases reports and a review of the French pharmacovigilance database

While physicians increasingly recognize nicorandil-related mucocutaneous ulcerations, there are still misdiagnoses, particularly in the case of unusual location and late onset ulceration after nicorandil introduction. The goal of our study was to remind clinicians about the link between nicorandil use and the development of cutaneous ulcerations and to highlight the risk of misdiagnosis. We describe five reports diagnosed by the same dermatologist, complemented by an analysis of the French pharmacovigilance database (FPVD) from 1 January 1994 to 5 January 2017. During this period, 28 reports of strict cutaneous ulcerations due to nicorandil, in addition to our five reports, were registered in the FPVD. For those 28 reports, the time to onset between nicorandil introduction and cutaneous ulcerations was quite long and exceeded one year in 16 reports (information specified in 25 reports). The delay between ulcerations observation and nicorandil discontinuation was variable, with immediate diagnosis in seven reports, but ranged from fifteen days to twelve years in 21 reports. The main locations were lower limbs, thorax and face. Ulcerations could be localized on surgery or trauma scars. Regression after nicorandil discontinuation was observed in all but two reports and ranged from three days to three months. Characteristics were comparable in our five patients series. All patients exposed to nicorandil and healthcare practitioners prescribing nicorandil should be aware of the risk of cutaneous ulcerations to enable early diagnosis and drug withdrawal. The risk of misdiagnosis of this serious adverse drug reaction, along with the risk of sequelae, the costs of unnecessary additional investigations and the recent update on nicorandil as second-line treatment for stable angina, with existing alternative drugs, question about the benefit/risk balance of nicorandil.

Evaluating Twitter as a complementary data source for pharmacovigilance

ABSTRACT 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.

39. Colchicine-Induced Pancytopenia During Therapeutic Dose Administration. French Pharmacovigilance Database Survey and Literature Review

Colchicine is an antimitotic agent, highly effective in the treatment ofmicrocrystalline arthritis, Behcet’s disease and familial Mediterranean fever.Pancytopenia by bone-marrow depression is common after colchicine overdose andintoxication. It is less common at therapeutic dose and it may be fatal. Colchicine hasa low narrow therapeutic range.