Individual Case Safety Reports Research Articles

Antipsychotic-Related DRESS Syndrome: Analysis of Individual Case Safety Reports of the WHO Pharmacovigilance Database.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is gaining attention in pharmacovigilance, but its association with antipsychotics, other than clozapine, is still unclear. We conducted a case/non-case study with disproportionality analysis based on the World Health Organization (WHO) global spontaneous reporting database, VigiBase®. We analyzed individual case safety reports of DRESS syndrome related to antipsychotics compared to (1) all other medications in VigiBase®, (2) carbamazepine (a known positive control), and (3) within classes (typical/atypical) of antipsychotics. We calculated reporting odds ratio (ROR) and Bayesian information component (IC), with 95% confidence intervals (CIs). Disproportionate reporting was prioritized based on clinical importance, according to predefined criteria. Additionally, we compared characteristics of patients reporting with serious/non-serious reactions. A total of 1534 reports describing DRESS syndrome for 19 antipsychotics were identified. The ROR for antipsychotics as a class as compared to all other medications was 1.0 (95% CI 0.9-1.1). We found disproportionate reporting for clozapine (ROR 2.3, 95% CI 2.1-2.5; IC 1.2, 95% CI 1.1-1.3), cyamemazine (ROR 2.3, 95% CI 1.5-3.5; IC 1.2, 95% CI 0.5-1.7), and chlorpromazine (ROR 1.5, 95% CI 1.1-2.1; IC 0.6, 95% CI 0.1-1.0). We found 35.7% of cases with co-reported anticonvulsants, and 25% with multiple concurrent antipsychotics in serious compared to 8.6% in non-serious cases (p = 0.03). Fatal cases were 164 (10.7%). Apart from the expected association with clozapine, chlorpromazine and cyamemazine (sharing an aromatic heteropolycyclic molecular structure) emerged with a higher-than-expected reporting of DRESS. Better knowledge of the antipsychotic-related DRESS syndrome should increase clinicians' awareness leading to safer prescribing of antipsychotics.

The Reporting of a Disproportionality Analysis for Drug Safety Signal Detection Using Individual Case Safety Reports in PharmacoVigilance (READUS-PV): Development and Statement.

Disproportionality analyses using reports of suspected adverse drug reactions are the most commonly used quantitative methods for detecting safety signals in pharmacovigilance. However, their methods and results are generally poorly reported in published articles and existing guidelines do not capture the specific features of disproportionality analyses. We here describe the development of a guideline (REporting of A Disproportionality analysis for drUg Safety signal detection using individual case safety reports in PharmacoVigilance [READUS-PV]) for reporting the results of disproportionality analyses in articles and abstracts. We established a group of 34 international experts from universities, the pharmaceutical industry, and regulatory agencies, with expertise in pharmacovigilance, disproportionality analyses, and assessment of safety signals. We followed a three-step process to develop the checklist: (1) an open-text survey to generate a first list of items; (2) an online Delphi method to select and rephrase the most important items; (3) a final online consensus meeting. Among the panel members, 33 experts responded to round 1 and 30 to round 2 of the Delphi and 25 participated to the consensus meeting. Overall, 60 recommendations for the main body of the manuscript and 13 recommendations for the abstracts were retained by participants after the Delphi method. After merging of some items together and the online consensus meeting, the READUS-PV guidelines comprise a checklist of 32 recommendations, in 14 items, for the reporting of disproportionality analyses in the main body text and four items, comprising 12 recommendations, for abstracts. The READUS-PV guidelines will support authors, editors, peer-reviewers, and users of disproportionality analyses using individual case safety report databases. Adopting these guidelines will lead to more transparent, comprehensive, and accurate reporting and interpretation of disproportionality analyses, facilitating the integration with other sources of evidence.

The REporting of A Disproportionality Analysis for DrUg Safety Signal Detection Using Individual Case Safety Reports in PharmacoVigilance (READUS-PV): Explanation and Elaboration.

In pharmacovigilance, disproportionality analyses based on individual case safety reports are widely used to detect safety signals. Unfortunately, publishing disproportionality analyses lacks specific guidelines, often leading to incomplete and ambiguous reporting, and carries the risk of incorrect conclusions when data are not placed in the correct context. The REporting of A Disproportionality analysis for drUg Safety signal detection using individual case safety reports in PharmacoVigilance (READUS-PV) statement was developed to address this issue by promoting transparent and comprehensive reporting of disproportionality studies. While the statement paper explains in greater detail the procedure followed to develop these guidelines, with this explanation paper we present the 14 items retained for READUS-PV guidelines, together with an in-depth explanation of their rationale and bullet points to illustrate their practical implementation. Our primary objective is to foster the adoption of the READUS-PV guidelines among authors, editors, peer reviewers, and readers of disproportionality analyses. Enhancing transparency, completeness, and accuracy of reporting, as well as proper interpretation of their results, READUS-PV guidelines will ultimately facilitate evidence-based decision making in pharmacovigilance.

Trends in Adverse Event Reporting Before and After the Introduction of the Med Safety App in Nigeria.

Spontaneous reporting of adverse events (AEs) is a mainstay of pharmacovigilance, and an ongoing challenge is how to ensure that more high-quality reports are collected for comprehensive information provision. The Med Safety App, a smartphone-based application, was launched in Nigeria in November 2020 to provide an electronic platform for users to seamlessly report AEs. There has been a paucity of evidence on the use of this application or other mobile applications for reporting adverse drug reactions/AEs following immunization in the Nigerian environment. The aim of this study was to evaluate the trends in adverse event reporting before and after the introduction of the Med Safety App in Nigeria. This was a retrospective, observational study using data from the VigiFlow database to compare adverse event reporting in Nigeria before and after the deployment of the Med Safety App. The baseline period was 1st April 2019to 30th October 2020 and the comparison period was 1st November 2020to 31st May 2022. We used Vigilance Hub, the back-end system for the Med Safety App, to extract data on App downloads and de-identified user statistics. Data were summarized using descriptive statistics, frequencies and proportions. Quality was assessed by assigning a completeness score to each individual case safety report. The Kruskal-Wallis test was used to test for differences in medians between groups. Following deployment of the App, the Nigerian National Pharmacovigilance Centre recorded an increase in the total number of adverse event reports received in VigiFlow, from 2051 in the baseline period to 18,995 following deployment of the App, with 81.7% of those reported via the Med Safety App. There was a reduction in the proportion of paper-based reporting from 98.4 to 15.7% post-deployment, and direct reporting by consumers increased from 2.7 to 17.6%. Of the 15,526 reports submitted via the App, 15,111 (97.3%) had a completeness score above 70% and 6993 (45%) had a completeness score of 100%. The median completeness score of adverse event reports on the Med Safety App was 6 out of 7. On bivariate analysis using the Kruskal-Wallis test, there was an association between means of reporting and completeness score, and this association was significant, with a p value of 0.0001, which may reflect the validation rules that are applied within the App. Deployment of the Med Safety App increased both the number and quality of adverse event reports; however, more awareness and capacity building are needed to strengthen and sustain reporting on the tool by all categories of healthcare professionals and consumers/patients.

Emerging Toxicities of Antibody-Drug Conjugates for Breast Cancer: Clinical Prioritization of Adverse Events from the FDA Adverse Event Reporting System.

Antibody-drug conjugates (ADCs) are gaining widespread use in the treatment of breast cancer, although toxicity remains an underexplored issue in the real-world clinical setting. Individual case safety reports collected in large pharmacovigilance databases can advance our knowledge on their safety profile in routine clinical practice. We prioritized adverse events (AEs) reported with ADCs approved for breast cancer using the Food andDrugAdministration Adverse Event Reporting System (FAERS). We assessed clinical priority of AEs reported in FAERS (February 2013-March 2022) for trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd), and sacituzumab govitecan (SG) by attributing a score to each AE disproportionally reported with ADCs. Four criteria were assessed: clinical relevance, reporting rate, reported case fatality rate, and stability of disproportionality signals (consistency of the reporting odds ratio across multiple analyses using three different comparators). We retained 6589 reports (77.4% referring to T-DM1 as suspect), and 572 AEs generated a disproportionality signal in at least one analysis. The majority of these AEs (62%) were classified as moderate clinical priorities (e.g., interstitial lung disease with T-DXd, thrombocytopenia, peripheral neuropathy with T-DM1, febrile neutropenia, and large intestine perforation with SG). Three AEs emerged as high clinical priorities (6 points): septic shock and neutropenic colitis with SG (N = 8 and 13, with median onset 13 and 10 days, respectively), without co-reported immunosuppressive agents; and pulmonary embolism with T-DM1 (N = 31, median onset 109 days, 52% with reported metastasis). The heterogeneous spectrum of post-marketing toxicities for ADCs used in breast cancer, as emerging from the FAERS, is largely in line with preapproval evidence. Although causality cannot be proved, we call for increased awareness by oncologists on potential serious unexpected reactions, including early onset of septic shock and neutropenic colitis with SG, and late emergence of pulmonary embolism with T-DM1.

Enhancing the Efficiency of the Individual Case Safety Report (ICSR) Quality and Compliance through Automation.

Over the past few years, major inspection findings have been identified in the "management of adverse reactions" that may be due to increasing workload in pharmaceutical organizations impacting the correctness of information in individual case safety reports (ICSRs). Although retrospective quality check (Retro-QC) and late submission analyses are important steps in ensuring ICSR quality, their manual application poses several challenges that can be overcome through automation. To improve the efficiency of the Retro-QC analysis and late submission analysis using a computer-operated tool called Compliance and Metrics Management (CMM) tool, and to measure the tool's effectiveness in terms of productivity, time, and cost savings by comparing against the manual process. Time savings were calculated by measuring the difference in time taken during the manual process versus the automated process. Cost savings were measured in terms of hourly remuneration for the time saved. Productivity was calculated as the difference between the number of cases handled in the manual versus automated process. Thus, the overall efficiency was measured in terms of time and cost savings along with increased productivity. Automation resulted in time savings of 49% and cost savings of 43% for Retro-QC analysis, and the productivity level increased by 67%. For late submission analysis, the CMM tool resulted in time savings of 88% and cost savings of 87%. CMM tool enhanced the efficiency of both Retro-QC and late submission analyses by increasing productivity along with time and cost savings. It also reduced the number of errors, thereby enhancing the accuracy of the process and overall compliance.

Exploring Adverse Drug Reactions in Psychotropic Medications: A Retrospective Analysis of Portuguese Pharmacovigilance Data.

Psychotropic drugs (PDs) include anxiolytics, sedatives and hypnotics, antidepressants, and antipsychotics, and they are available as medicines with different safety profiles. Given Portugal's high anxiolytic consumption and the rising prevalence of mental disorders, safety monitoring is crucial. This study aimed to analyze the individual case safety reports (ICSR) of suspected adverse drug reactions (ADRs) related to PDs, obtained through spontaneous reporting, and recorded in the Portuguese National Pharmacovigilance System between January 2017 and December 2021. This observational and retrospective study analyzed the ICSRs of suspected ADRs to PDs. Most reports pertained to female individuals (67.78%) between 18 and 64 years of age (63.71%). The pharmaceutical industry was the primary source of these reports (62.16%). Antidepressants were responsible for most ICSRs (61.90%). At least one serious ADR was recorded in 58.44% of the reports, and 43.84% of ADRs evolved into "cure". The most-observed ADRs were nausea (10.92%), dizziness (10.70%), and off-label use (10.30%). In the causality assessment, 45.49% of ADRs were classified as "possible", and only 4.96% were classified as "definitive". The current analysis helps to strengthen the safety evidence for PDs. In the future, some measures could be implemented to improve the use of and/or access to PDs, as well as to reinforce the rate of suspected ADR reports within the community, contributing to the safety data available.

Regional Differences in GLP-1 Receptor Agonists Related Biliary Disease: A Pharmacovigilance Study of VigiBase®

Glucagon-like peptide-1 receptor agonists are highly recommended for treatment of type 2 diabetes as one of the second-line therapies with additional benefits of cardiorenal disease. Despite the diverse therapeutic advantages, safety issues remain controversial regarding the pancreatic-related adverse events associated with the use of incretin-based drugs. We aimed to examine regional differences in biliary diseases related safety for GLP-1 RAs compared with all other antidiabetic drugs. In this study, individual case safety reports for GLP-1 RAs and comparison group were retrieved from the World Health Organization’s global database, VigiBase during 2005 to 2023. Disproportionality analysis was performed to examine Reporting odds ratio and 95% confidence interval for each adverse event of interest, adjusted for sex and age group by using logistic regression. Disproportionate reporting was observed in America for biliary track disorders associated with the GLP-1 RAs compared with all other antidiabetic drugs. However, for gallbladder-related disorders, an increased risk was identified in most regions (America: ROR 2.34; 95%CI 2.06-2.66, Europe: ROR 5.71; 4.62-7.05, Asia: ROR 4.12; 2.98-5.69). As this study cannot determine the causality between GLP-1 RAs and the biliary disease, a multinational confirmatory study is inevitable to validate the regional differences in the association between GLP-1 RAs and biliary disease.

Artificial intelligence in pharmacovigilance – Opportunities and challenges

Abstract Pharmacovigilance (PV) is a data-driven process to identify medicine safety issues at the earliest by processing suspected adverse event (AE) reports and extraction of health data. The PV case processing cycle starts with data collection, data entry, initial checking completeness and validity, coding, medical assessment for causality, expectedness, severity, and seriousness, subsequently submitting report, quality checking followed by data storage and maintenance. This requires a workforce and technical expertise and therefore, is expensive and time-consuming. There has been exponential growth in the number of suspected AE reports in the PV database due to smart collection and reporting of individual case safety reports, widening the base by increased awareness and participation by health-care professionals and patients. Processing of the enormous volume and variety of data, making its sensible use and separating “needles from haystack,” is a challenge for key stakeholders such as pharmaceutical firms, regulatory authorities, medical and PV experts, and National Pharmacovigilance Program managers. Artificial intelligence (AI) in health care has been very impressive in specialties that rely heavily on the interpretation of medical images. Similarly, there has been a growing interest to adopt AI tools to complement and automate the PV process. The advanced technology can certainly complement the routine, repetitive, manual task of case processing, and boost efficiency; however, its implementation across the PV lifecycle and practical impact raises several questions and challenges. Full automation of PV system is a double-edged sword and needs to consider two aspects – people and processes. The focus should be a collaborative approach of technical expertise (people) combined with intelligent technology (processes) to augment human talent that meets the objective of the PV system and benefit all stakeholders. AI technology should enhance human intelligence rather than substitute human experts. What is important is to emphasize and ensure that AI brings more benefits to PV rather than challenges. This review describes the benefits and the outstanding scientific, technological, and policy issues, and the maturity of AI tools for full automation in the context to the Indian health-care system.

Real-World Safety Data of the Orphan Drug Onasemnogene Abeparvovec (Zolgensma®) for the SMA Rare Disease: A Pharmacovigilance Study Based on the EMA Adverse Event Reporting System.

The recent introduction of the innovative therapy, onasemnogene abeparvovec (Zolgensma®), has revolutionized the spinal muscular atrophy (SMA) therapeutic landscape. Although Zolgensma® therapy has proven to lead to functional improvements in SMA children, some gaps in its safety profile still need to be investigated. To better characterize the Zolgensma® safety profile, we conducted a retrospective observational study, analyzing all the Individual Case Safety Reports (ICSRs) referred to it and collected in the European pharmacovigilance database between 1 January 2019 and 22 September 2023. We found 661 ICSRs related to Zolgensma®, with a growing trend in the annual reporting. The majority of the reports were sent by healthcare professionals and referred to infant females. In more than 90% of the cases, Zolgensma® was the only reported suspected drug. Out of a total of 2744 reported ADRs, increased hepatic enzymes, pyrexia, vomiting, and thrombocytopenia were the most commonly reported adverse reactions. Of these adverse reactions (ADRs), 56.9% were serious, causing or prolonging the patient's hospitalization. A total of 39 ICSRs related to cases with a fatal outcome. Alterations in the heart rhythm, acute hepatic failure, and hepatic cytolysis emerged among the cardiac and hepatic disorders, respectively.

Safety of Biological Therapies for Severe Asthma: An Analysis of Suspected Adverse Reactions Reported in the WHO Pharmacovigilance Database.

The management of uncontrolled severe asthma has greatly improved since the advent of novel biologic therapies. Up to August 2022, five biologics have been approved for the type 2 asthma phenotype: anti-IgE (omalizumab), anti-IL5 (mepolizumab, reslizumab, benralizumab), and anti-IL4 (dupilumab) monoclonal antibodies. These drugs are usually well tolerated, although long-term safety information is limited, and some adverse events have not yet been fully characterized. Spontaneous reporting systems represent the cornerstone for the detection of potential signals and evaluation of the real-world safety of all marketed drugs. The aim of this study was to provide an overview of safety data of biologics for severe asthma using VigiBase, the World Health Organization global pharmacovigilance database. We selected all de-duplicated individual case safety reports (ICSRs) attributed to five approved biologics for severe asthma in VigiBase, up to 31st August 2022 (omalizumab, mepolizumab, reslizumab, benralizumab and dupilumab). Descriptive frequency analyses of ICSRs were carried out both as a whole class and as individual products. Reporting odds ratios (ROR) with 95% confidence intervals (CIs) were used as the measure of disproportionality for suspected adverse drug reactions (ADRs) associated with the study drugs compared with either all other suspected drugs (Reference Group 1, RG1) or inhaled corticosteroids plus long-acting β-agonists (ICSs/LABAs) (Reference Group 2, RG2) or with oral corticosteroids (OCSs) (Reference Group 3, RG3). Overall, 31,724,381 ICSRs were identified in VigiBase and 167,282 (0.5%) were related to study drugs; the remaining reports were considered as RG1. Stratifying all biologic-related ICSRs by therapeutic indication, around 29.4% (n = 48,440) concerned asthma use; omalizumab was mainly indicated as the suspected drug (n = 20,501), followed by dupilumab, mepolizumab, benralizumab and reslizumab. Most asthma ICSRs concerned adults (57%) and women (64.1%). Asthma biologics showed a higher frequency of serious suspected ADR reporting than RG1 (41.3% vs 32.3%). The most reported suspected ADRs included asthma, dyspnea, product use issue, drug ineffective, cough, headache, fatigue and wheezing. Asthma biologics were disproportionally associated with several unknown or less documented adverse events, such as malignancies, pulmonary embolism and deep vein thrombosis with omalizumab; alopecia and lichen planus with dupilumab; alopecia and herpes infections with mepolizumab; alopecia, herpes zoster and eosinophilic granulomatosis with polyangiitis related to benralizumab; and alopecia with reslizumab. The most frequently reported suspected ADRs of asthma biologics in VigiBase confirmed the presence of well-known adverse effects such as general disorders, injection-site reactions, nasopharyngitis, headache and hypersensitivity, while some others (e.g. asthma reactivation or therapeutic failure) could be ascribed to the indication of use. Moreover, the analysis of signals of disproportionate reporting suggests the presence of malignancies, effects on the cardiovascular system, alopecia and autoimmune conditions, requiring further assessment and investigation.

Serious Safety Signals and Prediction Features Following COVID-19 mRNA Vaccines Using the Vaccine Adverse Event Reporting System.

We aimed to analyze the characteristics of serious adverse events following immunizations (AEFIs) to identify potential safety information and prediction features. We screened the individual case safety reports (ICSRs) in adults who received mRNA-based COVID-19 vaccines using the Vaccine Adverse Event Reporting System until December 2021. We identified the demographic and clinical characteristics of ICSRs and performed signal detection. We developed prediction models for serious AEFIs and identified the prognostic features using logistic regression. Serious ICSRs and serious AEFIs were 51,498 and 271,444, respectively. Hypertension was the most common comorbidity (22%). Signal detection indicated that the reporting odds ratio of acute myocardial infarction (AMI) was more than 10 times. Those who had experienced myocardial infarction (MI) were 5.7 times more likely to suffer from MI as an AEFI (95% CI 5.28-6.71). Moreover, patients who had atrial fibrillation (AF), acute kidney injury (AKI), cardiovascular accident (CVA), or pulmonary embolism (PE) were 7.02 times, 39.09 times, 6.03 times, or 3.97 times more likely to suffer from each AEFI, respectively. Our study suggests that vaccine recipients who had experienced MI, AF, AKI, CVA, or PE could require further evaluation and careful monitoring to prevent those serious AEFIs.

Investigating the safety profiles of exogenous melatonin and associated adverse events: A pharmacovigilance study using WHO-VigiBase.

Melatonin, a pineal hormone that modulates circadian rhythms, sleep, and neurotransmitters, is widely used to treat sleep disorders. However, there are limited studies on the safety of melatonin. Therefore, we aimed to present the overall patterns of adverse events (AEs) following melatonin administration and identify potential safety signals associated with melatonin. Using VigiBase, a global individual case safety report (ICSRs) database managed by the World Health Organization (WHO), we conducted a retrospective, observational, pharmacovigilance study of melatonin between January 1996 and September 2022. Disproportionality analysis was conducted using two comparator settings: all other drugs and other sleep medications. We used multivariable logistic regression to estimate reporting odds ratios (RORs) with 95% confidence intervals (CIs) to compare the frequencies of AEs reporting between melatonin and each comparator setting. Furthermore, we assessed adverse events of special interests (AESIs) that could potentially be associated with melatonin. Signals were identified when the following criteria were met: cases ≥3, x2 ≥ 4, IC025 ≥ 0, and the lower end of the 95% CI of ROR > 2. These signals were then compared with the AE information on the drug labels provided by regulatory bodies. A total of 35 479 AE reports associated with melatonin were identified, with a higher proportion of reports from females (57.1%) and individuals aged 45-64 years (20.8%). We identified 21 AEs that were commonly detected as safety signals in the disproportionality analyses, including tic, educational problems, disturbance in social behavior, body temperature fluctuation, and growth retardation. In AESI analyses, accidents and injuries (adjusted ROR 2.97; 95% CI, 2.80-3.16), fall (2.24; 2.12-2.37), nightmare (4.90; 4.37-5.49), and abnormal dreams (3.68; 3.19-4.25) were detected as a signal of melatonin when compared to all other drugs, whereas those signals were not detected when compared to other sleep medications. In this pharmacovigilance study, exogenous melatonin showed safety profiles comparable to other sleep medications. However, several unexpected potential safety signals were identified, underscoring the need for further investigation at the population level.

Cardiovascular Adverse Drug Reactions of Anti-Calcitonin Gene-Related Peptide Monoclonal Antibodies for Migraine Prevention: An Analysis from the European Spontaneous Adverse Event Reporting System.

Anti-calcitonin gene-related peptide monoclonal antibodies (anti-CGRP-mAbs) have recently been approved for the prevention of migraine, and their safety profile is not fully characterized. The aim of this study was to evaluate the adverse drug reactions (ADRs) of anti-CGRP-mAbs through the analysis of individual case safety reports (ICSRs) collected in the EudraVigilance (EV) database, with a specific focus on cardiovascular (CV) ADRs. Data on ICSRs recorded between July 2018 and December 2022 in the EV database, involving one of the anti-CGRP-mAbs for migraine prevention-erenumab (ERE), galcanezumab (GMB), fremanezumab (FMB), and eptinezumab (EPT)-were included in the analysis. All ICSRs reporting at least one CV ADR, as identified within the MedDRA® System Organ Classes (SOCs) "cardiac disorders" or "vascular disorders," were selected for the analysis. The frequency of disproportionate reporting was expressed as the reporting odds ratio (ROR) with its 95% confidence interval (CI), to evaluate the frequency of reporting of CV ADRs for each anti-CGRP-mAb compared with all other monoclonal antibodies (mAbs). A case-by-case analysis was conducted paying particular attention to serious CV ADR reports, focusing on the type of seriousness, age group, sex, and concomitant drugs. A total of 9441 ICSRs were recorded in the EV database from 2018 to 2022, of which more than half were related to ERE (58.9%), followed by GMB (21.4%), FMB (19.0%), and EPT (0.7%). CV ICSRs accounted for 1205 cases (12.8%), with a total of 1599 CV ADRs. The CV ICSRs were mainly related to female patients (82.6%) aged 18-64 years (73.4%). Of the reported CV ADRs, 67.5% were considered serious. Among the total number of ICSRs related to each anti-CGRP-mAb, those associated with FMB had a higher percentage of CV ADRs (n = 253; 14.1%), followed by ERE (n = 707; 12.7%), EPT (n = 8; 12.7%), and GMB (n = 237; 11.7%). A higher frequency of reporting hypertension was shown for ERE (ROR = 1.45; 95% CI = 1.14-1.85). Pallor was mainly observed with FMB (5.00; 1.68-14.89), as well as deep vein thrombosis (3.86; 1.57-9.51), hot flush (2.16; 1.43-3.25), and palpitations (1.48; 1.05-2.08). Atrial fibrillation (2.36; 1.02-5.46) and myocardial infarction (2.21; 1.37-3.58) were mostly reported for GMB. The analysis of anti-CGRP-related CV ADRs was consistent with the information reported in the literature. However, hypertension with ERE, atrial fibrillation and myocardial infarction with GMB, as well as pallor, deep vein thrombosis, hot flush, and palpitations with FMB were not reported in the Summary of Product Characteristics (SmPCs). Considering this, more post-marketing analyses are needed to improve knowledge on the CV safety profiles of anti-CGRP-mAbs, especially for the last approved medication, EPT.

Adverse events following immunization reported with COVID-19 vaccines in Burkina Faso: Analysis of spontaneous reports

The rapid deployment of COVID-19 vaccines to a large proportion of the population requires a focus on safety. However, few studies have assessed the safety of COVID-19 vaccines in Africa. In Burkina Faso, this issue has not yet been addressed. The objective of this study was to contribute to the description of the characteristics of adverse events following immunization (AEFIs) related to COVID-19 vaccines in Burkina Faso. This was a cross-sectional descriptive retrospective study of spontaneous reports of COVID-19 vaccine-related AEFIs recorded in VigiBase® between June 2021 and November 2022 in Burkina Faso. Individual case safety reports (ICSRs) were extracted from VigiBase® using the Anatomical Therapeutic Chemical level 2 (ATC2) code. The proportion of ICSRs according to the reporter’s qualification, the reporting rate, the time taken to submit and record ICSRs, and the completeness score were calculated. A total of 973 ICSRs concerned COVID-19 vaccines and represented 32.6% of all 2,988 reports in VigiBase®. Overall, 82.0% of the reporters were nurses/midwives, 7.8% were physicians, 6.7% were pharmacists, and 3.4% were patients. The median time between the onset of AEFIs and the submission of the report to the Pharmacovigilance Center was 180 days (IQR: 136; 281). The median registration time was 188 days (IQR: 149; 286). The mean ICSR completeness score was 0.8 (standard deviation = 0.1). The overall AEFI reporting rate was 27.8 per 100,000 vaccine doses. The AEFI reporting rates for the ChAdOx1-nCoV-19, JNJ 78436735, Elasomeran, Tozinameran, and HB02 vaccines were 454.2, 17.4, 11.0, 10.2, and 0.4 per 100,000 vaccine doses, respectively. The majority of AEFIs were systemic in nature (90.1%). Headache (21.2%), fever (19.4%), and myalgia (11.0%) were the most frequently reported AEFIs. Eighteen cases (1.8%) of serious AEFIs (9 hospitalizations, 4 life threatening, 3 temporary disabilities, and 2 others unspecified) were reported. The majority of AEFIs reported were systemic in nature and mild. However, there have been reports of serious AEFIs. The overall AEFI reporting rate was low. There is a need to strengthen the monitoring of these vaccines to better organize strategies to optimize the adherence of the population of Burkina Faso.

Comparison of WHO-UMC and Naranjo Scales for Causality Assessment of Reported Adverse Drug Reactions.

The 2 most commonly used scales worldwide are the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) and the Naranjo scales. The present study was planned to assess the degree of agreement between the 2 scales when the same adverse drug reactions (ADR) were assessed by 5 raters independently. One hundred individual case safety reports were selected randomly from the ADR database of our institute and the details were emailed to 5 different experts (raters), who were DM Clinical Pharmacology residents from different institutes in India. An independent causality assessment of these ADRs was performed independently by these raters using both the WHO-UMC and Naranjo causality assessment scales. The agreement between the 2 scales was assessed for each rater using Cohen κ, and the overall interrater agreement was assessed using Fleiss κ. The Cohen κ level of agreement between the 2 scales for the 5 raters were substantial, fair, substantial, moderate, and substantial, respectively. The most common causality assessment category as per WHO-UMC scale was "possible" but varied among the raters on the Naranjo scale. No ADR was categorized as "certain" by any rater on the Naranjo scale. The Fleiss κ value for agreement among the 5 raters was found to be 0.2 (slight) for the WHO-UMC scale and 0.297 (fair) for the Naranjo scale. A moderate level of agreement was observed in this study between the WHO-UMC and Naranjo scales. The level of agreement among these 5 raters was found to be similar for the WHO-UMC and the Naranjo scales, indicating a similar degree of subjectivity for the 2 scales. Hence, more robust and less subjective scales are required for causality assessment.

Comparison of agranulocytosis and anti‐neutrophil cytoplasmic antibody‐associated vasculitis caused by two antithyroid drugs: A pharmacovigilance study using the WHO international database

AbstractBackgroundMethimazole (MMI) and propylthiouracil (PTU) are commonly used for patients with thyrotoxicosis. Agranulocytosis and antineutrophil cytoplasmic antibody (ANCA)‐associated vasculitis (AAV) is associated with high morbidity and mortality, requiring appropriate interventions. In this study, we compared adverse drug effects associated with MMI and PTU using a real‐world large pharmacovigilance database.MethodsWe searched all Individual Case Safety Reports reported to be associated with MMI and PTU, from VigiBase between 1967 and June 2, 2021. We conducted disproportionality analysis (case/non‐case analysis) to analyze the difference in reported adverse drug reactions (ADRs) between antithyroid drugs (case) and the entire database (non‐cases). We further analyzed information for the cases of agranulocytosis and AAV.ResultsAmong 11 632 cases of ADRs reported after MMI intake, agranulocytosis occurred in 1633 cases and AAV occurred in 41 cases. For 5055 cases of ADRs reported after PTU intake, agranulocytosis occurred in 459 cases and AAV occurred in 110 cases. Agranulocytosis occurred after a median of 28 days after PTU intake and 33 days after MMI intake. More than 95% of the agranulocytosis cases were classified as serious, but most of them (65.1% for PTU and 70.4% for MMI) were reported to have recovered after dechallenge actions; mostly drug withdrawal. AAV occurred after a median of 668 days after PTU intake, and 1162 days after MMI intake.ConclusionsThis is a pharmacoepidemiological study investigating agranulocytosis and AAV caused by MMI and PTU. Through this research, we could provide more specific insights into a safe prescription of antithyroid drugs in a real‐world setting.

A Real-World Study on the Clinical Characteristics, Outcomes, and Relationship between Antibiotic Exposure and Clostridioides difficile Infection.

Clostridioides difficile is a Gram-positive bacteria that causes nosocomial infections, significantly impacting public health. In the present study, we aimed to describe the clinical characteristics, outcomes, and relationship between antibiotic exposure and Clostridioides difficile infection (CDI) in patients based on reports from two databases. Thus, we conducted a retrospective study of patients diagnosed with CDI from Sibiu County Clinical Emergency Hospital (SCCEH), Romania, followed by a descriptive analysis based on spontaneous reports submitted to the EudraVigilance (EV) database. From 1 January to 31 December 2022, we included 111 hospitalized patients with CDI from SCCEH. Moreover, 249 individual case safety reports (ICSRs) from EVs were analyzed. According to the data collected from SCCEH, CDI was most frequently reported in patients aged 65-85 years (66.7%) and in females (55%). In total, 71.2% of all patients showed positive medical progress. Most cases were reported in the internal medicine (n = 30, 27%), general surgery (n = 26, 23.4%), and infectious disease (n = 22, 19.8%) departments. Patients were most frequently exposed to ceftriaxone (CFT) and meropenem (MER). Also, in the EV database, most CDI-related ADRs were reported for CFT, PIP/TAZ (piperacillin/tazobactam), MER, and CPX (ciprofloxacin). Understanding the association between previous antibiotic exposure and the risk of CDI may help update antibiotic stewardship protocols and reduce the incidence of CDI by lowering exposure to high-risk antibiotics.

Assessment of pharmacovigilance guidelines in the Southern African Development Community: A document review.

Lack of harmonization in pharmacovigilance (PV) practice in resource-limited states in Africa has led to differentiation and marginalization, thus creating an environment where weak or absent PV systems may benefit from regional guidelines. To compare the PV guidelines of Southern African Development Community (SADC) member states to international guidelines and identify areas for improvement for aligning PV practice within the SADC region. We utilized a 73-item checklist to assess the PV guidelines of the SADC member states. Checklist parameters were rated using binary scoring. Only seven (Botswana, Mauritius, Namibia, South Africa, Tanzania, Zambia, and Zimbabwe) of the 16 SADC member states had guidelines to assess. Of these, only four had supporting legislation. All seven national medicines regulatory authorities (NMRA)'s guidelines required reporting of local serious adverse drug reactions (ADRs). Four NMRAs implemented device vigilance; none specified submission timelines for ADRs associated with substandard or falsified medicines. Only three NMRAs required electronic transmission of individual case safety reports in the E2B format. Five NMRAs mandated safety monitoring during interventional clinical trials. Five NMRAs required aggregate reporting through periodic safety update reports. Only two NMRAs required submission of the development safety update report. Regarding risk management, four NMRAs required notification of actions taken by foreign NMRAs and four NMRAs expected to review Dear Healthcare Professional Letters before distribution by the marketing authorization holder. Areas for improvement of guidelines to establish common process standards and allow for synchronized submissions of comparable data to SADC NMRAs are provided.

Psychiatric adverse events associated with semaglutide, liraglutide and tirzepatide: a pharmacovigilance analysis of individual case safety reports submitted to the EudraVigilance database

BackgroundSemaglutide, liraglutide and tirzepatide are glucagon-like peptide-1 (GLP-1) receptor agonists that are effective for weight reduction. Recent reports of patients experiencing suicidal thoughts and other psychiatric adverse events while using GLP-1 agonists have raised concerns about the potential risk of self-harm and led the European Medicines Agency to investigate these medications.AimTo identify and analyse the psychiatric adverse events associated with semaglutide, liraglutide and tirzepatide.MethodAll individual case safety reports for semaglutide, liraglutide, and tirzepatide reported to the EudraVigilance database from 01/01/2021 to 30/05/2023 were analysed. Descriptive statistics were used to explore study population characteristics.ResultsDuring the study period, 31,444 adverse event reports were identified: semaglutide (n = 13,956; 44.4%), liraglutide (n = 16,748; 53.2%), and tirzepatide (n = 740; 2.3%). There were 372 reports with psychiatric adverse event reports (n = 372; 1.18%) with a total of 481 adverse events. Women accounted for 65% (n = 242) of these reports. Depression was the most commonly reported adverse event (n = 187; 50.3%), followed by anxiety (n = 144; 38.7%) and suicidal ideation (n = 73; 19.6%). Nine deaths (8 with liraglutide and 1 with semaglutide) and 11 life-threatening outcomes (4 associated with liraglutide and 7 with semaglutide) were reported. The fatal outcomes occurred primarily among men (8 out of 9) resulting from completed suicidal attempts and depression.ConclusionPsychiatric adverse events comprised only 1.2% of the total reports for semaglutide, liraglutide, and tirzepatide. However, the severity and fatal outcomes of some of these reports warrant further investigation.