Spontaneous Reports Research Articles

A real-world pharmacovigilance study of drug-induced QT interval prolongation: analysis of spontaneous reports submitted to FAERS.

To identify the most commonly reported drugs associated with QT interval prolongation in the FDA Adverse Event Reporting System (FAERS) and evaluate their risk for QT interval prolongation. We employed the preferred term (PT) "electrocardiogram QT prolonged" from the Medical Dictionary for Regulatory Activities (MedDRA) 26.0 to identify adverse drug events (ADEs) of QT interval prolongation in the FAERS database from the period 2004-2022. Reporting odds ratio (ROR) was performed to quantify the signals of ADEs. We listed the top 40 drugs that caused QT interval prolongation. Among them, the 3 drugs with the highest number of cases were quetiapine (1,151 cases, ROR = 7.62), olanzapine (754 cases, ROR = 7.92), and citalopram (720 cases, ROR = 13.63). The two most frequently reported first-level Anatomical Therapeutic Chemical (ATC) groups were the drugs for the nervous system (n = 19, 47.50%) and antiinfectives for systemic use (n = 7, 17.50%). Patients with missing gender (n = 3,482, 23.68%) aside, there were more females (7,536, 51.24%) than males (5,158, 35.07%) were involved. 3,720 patients (25.29%) suffered serious clinical outcomes resulting in deaths or life-threatening conditions. Overall, most drugs that caused QT interval prolongation had early failure types according to the assessment of the Weibull's shape parameter (WSP) analysis. Our study offered a list of drugs that frequently caused QT interval prolongation based on the FAERS system, along with a description of some risk profiles for QT interval prolongation brought on by these drugs. When prescribing these drugs in clinical practice, we should closely monitor the occurrence of ADE for QT interval prolongation.

Analysis of local anesthetics side effects and determination of ways for their minimization

According to the World Health Organization (WHO), the development of side effects of drugs is one of the serious medical problems.The relevance of this problem is proven by numerous statistical data obtained in different countries of the world. The aim of the study was to determine the assortment of local anesthetics (LAs) on the pharmaceutical market of Ukraine, to analyze the evidence base of the effectiveness and safety of modern LAs, to monitor the side effects (SEs) of LAs in Kharkiv and Kharkiv region for the period 2018–2021, and to provide recommendations for their minimization. The methods of passive pharmacovigilance, method of spontaneous reports, method of system approach and system analysis were used in the study. To analyze the clinical effectiveness and conditions of rational use of LAs, well-known data bases were used: Cochrane Library, Trip Database, and PubMed. These databases contain systematized primary or secondary information on a specific clinical issue: the effectiveness and safety of various medical technologies. The results of the analysis of the assortment of LAs on the pharmaceutical market of Ukraine showed that in 2023, based on 9 international non-patented names of LAs, 65 trade names were presented. Bupivacaine and procaine drugs (16 trade names each) and articaine drugs in combinations (13 trade names) are market leaders. The results of the analysis of notification cards with cases of SEs for 4 years revealed that the majority of them in the form of dizziness, weakness, changes in blood pressure, heart rate, edema, itching, hyperemia at the site of application were recorded when using lidocaine drugs, which are the most in demand and popular among doctors. According to the data of systematic reviews, the main directions for reducing the side effects of LAs have been established, such as administration under ultrasound control, the use of the least toxic modern anesthetics ropivacaine and levobupivacaine (not available on the Ukrainian market), the addition of substances with vasoconstrictive properties to the anesthetic solution, the use of combinations of long-acting and short-acting anesthetics. The results obtained can be used by practicing doctors and health care organizers to optimize LAs.

Comparators in Pharmacovigilance: A Quasi-Quantification Bias Analysis.

It is unclear which comparator is the most appropriate for bias reduction in disproportionality analyses based on spontaneous reports. We conducted a quasi-quantitative bias analysis using two well-studied drug-event combinations to assess how different comparators influence the directionality of bias in pharmacovigilance. We used the US Food and Drug Administration Adverse Event Reporting System focusing on two drug-event combinations with a propensity for stimulated reporting: rivaroxaban and hepatotoxicity, and canagliflozin and acute kidney injury. We assessed the directionality of three disproportionality analysis estimates (reporting odds ratio, proportional reporting ratio, information component) using one unrestricted comparator (full data) and two restricted comparators (active comparator, active comparator with class exclusion). Analyses were conducted within two calendar time periods, defined based on external events (approval of direct oral anticoagulants, Food and Drug Administration safety warning on acute kidney injury with sodium-glucose cotransporter 2 inhibitors) hypothesized to alter reporting rates. There were no false-positive signals for rivaroxaban and hepatotoxicity irrespective of the comparator. Restricting to the initial post-approval period led to false-positive signals, with restricted comparators performing worse. There were false-positive signals for canagliflozin and acute kidney injury, with restricted comparators performing better. Restricting to the period before the Food and Drug Administration warning weakened the false-positive signal for canagliflozin and acute kidney injury across comparators. We could not identify a consistent and predictable pattern to the directionality of disproportionality analysis estimates with specific comparators. Calendar time-based restrictions anchored on relevant external events had a considerable impact.

COVID-19 Vaccines and Heavy Menstrual Bleeding: The Impact of Media Attention on Reporting to EudraVigilance.

During the COVID-19 vaccination campaign, over 34,000 reports of heavy menstrual bleeding following the administration of COVID-19 vaccines originating in the Economic European Area were submitted to EudraVigilance, the European Union database of suspected adverse drug reactions. More than 90% of these reports were sent by consumers while the remaining by healthcare professionals. Public concerns regarding menstruation disorders in COVID-19 vaccinees were also covered by the media. We investigated the impact of media attention on the reporting trends of heavy menstrual bleeding to EudraVigilance. We used media outlets published in the Economic European Area on menstrual disorders and COVID-19 vaccines from the beginning of the vaccination campaign in the Economic European Area (1 January, 2021) until December 2022 (i.e., after the regulatory request to add the adverse event to the product information) and spontaneous reports from EudraVigilance. We found that the publication of safety updates from regulatory authorities and subsequent coverage in media outlets preceded increased reporting to EudraVigilance. Furthermore, the heavy menstrual bleeding reported in the cases occurred several weeks or months earlier and were not submitted to the respective date. The analysis suggests that the spikes in reporting of heavy menstrual bleeding were to some extent influenced by media coverage in some countries. Consumer reporting to the European Union spontaneous data collection system, EudraVigilance, was of high value for regulatory safety reviews, albeit the reporting behaviours were not free of the influence of the media. These sources of information can be investigated to understand the context of safety concerns of public health interest.

Lessons Learned on Observed-to-Expected Analysis Using Spontaneous Reports During Mass Vaccination.

During the COVID-19 vaccination campaign, observed-to-expected analysis was used by the European Medicines Agency to contextualise data from spontaneous reports to generate real-time evidence on emerging safety concerns that may impact the benefit-risk profile of COVID-19 vaccines. Observed-to-expected analysis compares the number of cases spontaneously reported for an event of interest after vaccination ('observed') to the 'expected' number of cases anticipated to occur in the same number of individuals had they not been vaccinated. Observed-to-expected analysis is a robust methodology that relies on several assumptions that have been described in regulatory guidelines and scientific literature. The use of observed-to-expected analysis to support the safety monitoring of COVID-19 vaccines has provided valuable insights and lessons on its design and interpretability, which could prove to be beneficial in future analyses. When undertaking an observed-to-expected analysis within the context of safety monitoring, several aspects need attention. In particular, we emphasise the importance of stratified and harmonised data collection both for vaccine exposure and spontaneous reporting data, the need for alignment between coding dictionaries and the crucial role of accurate background incidence rates for adverse events of special interest. While these considerations and recommendations were determined in the context of the COVID-19 mass vaccination setting, they are generalisable in principle.

Identifying Drug-Drug Interactions in Spontaneous Reports Utilizing Signal Detection and Biological Plausibility Aspects.

Translational approaches can benefit post-marketing drug safety surveillance through the growing availability of systems pharmacology data. Here, we propose a novel Bayesian framework for identifying drug-drug interaction (DDI) signals and differentiating between individual drug and drug combination signals. This framework is coupled with a systems pharmacology approach for automated biological plausibility assessment. Integrating statistical and biological evidence, our method achieves a 16.5% improvement (AUC: from 0.620 to 0.722) with drug-target-adverse event associations, 16.0% (AUC: from 0.580 to 0.673) with drug enzyme, and 15.0% (AUC: from 0.568 to 0.653) with drug transporter information. Applying this approach to detect potential DDI signals of QT prolongation and rhabdomyolysis within the FDA Adverse Event Reporting System (FAERS), we emphasize the significance of systems pharmacology in enhancing statistical signal detection in pharmacovigilance. Our study showcases the promise of data-driven biological plausibility assessment in the context of challenging post-marketing DDI surveillance.

Breastfeeding-Related Adverse Drug Reactions of Triptans: A Descriptive Analysis Using Four Pharmacovigilance Databases.

Objective: Migraine attacks are common in women of reproductive age. Although attacks are often less severe and less frequent during pregnancy, they regularly reoccur shortly after delivery. When first-line analgesic treatment is insufficient, triptans may be used for acute treatment of migraine attacks. Milk levels of occasional triptan use have shown to be low, and no adverse effects in breastfed infants have been reported. However, the available knowledge on the safety of triptans during breastfeeding is still limited. Methods: Four (inter)national pharmacovigilance databases were searched for breastfeeding related adverse drug reactions of triptans. These included the Dutch Pregnancy Drug Register and three databases of spontaneous reports (Netherlands Pharmacovigilance Centre Lareb, the European Medicines Agency [EudraVigilance], and the World Health Organization [VigiBase]). Results: A total of 26 reports on 27 breastfeeding related adverse drug reactions were identified (one report involved two separate adverse drug reactions). These involve three main complaints: painful breasts and/or nipples, painful milk ejection reflex, and a decrease in milk production. Discussion and Conclusion: The hypothesized pharmacological mechanism relates to the serotonin-receptor agonistic properties of triptans. These may lead to vasoconstriction in the breasts and nipples, including the vasculature surrounding the milk ducts and alveoli, and may also influence the hormonal function and levels of prolactin. The reported adverse drug reactions do not negatively impact the overall compatibility of triptans with breastfeeding. However, breastfeeding women may experience them as unsettling. Awareness of these potential adverse drug reactions is essential and should be weighed against the potential adverse effects of (untreated) symptoms of migraine attacks.

Analysis of drug-drug interactions in spontaneous adverse drug reaction reports from EudraVigilance focusing on psychiatric drugs and somatic medication

IntroductionPatients with severe mental illnesses (SMI) are often exposed to polymedication. Additionally, the risk of somatic diseases is twice as high in patients with SMI as in individuals without a psychiatric disorder. Furthermore, drug–drug interactions (DDI) between psychiatric drugs and somatic medications are a well-known cause of adverse drug reactions (ADR).ObjectivesThe aim of this study was to analyse whether already known DDI related to psychiatric drugs and somatic medication still occur in everyday clinical practice.MethodsTherefore we identified all spontaneous ADR reports contained in the European ADR database EudraVigilance from Germany received between 01/2017 and 12/2021 reported for patients older than 17 years in which antidepressants, antipsychotics and mood stabilizers were reported as suspected/interacting (n= 9,665). ADR reports referring to intentional overdoses and suicide attempts were excluded (n= 9,276 left). We used the ABDATA drug information system in order to identify all potential DDI (pDDI). The identified reports with pDDI were then assessed individually to determine whether the respective DDI occurred.Results 1,271 reports with 728 potentially interacting drugs pairs related to psychiatric drugs and somatic medications with 2,655 pDDI were found. Restricted to potentially interacting drug pairs with more than 10 reports, (i) hyponatremias related to antidepressants and diuretics (n= 362, 32.6%), (ii) bleeding events related to selective serotonin reuptake inhibitors (SSRI) and platelet aggregation inhibitors, anticoagulants or non-steroidal antiinflammatory drugs (NSAID) (n= 295, 17.5%), and (iii) increased beta-blocker effects related to SSRIs and beta-blockers (n= 126, 11.3%) were the most frequently identified pDDI. After individual case assessment, in 33.3% (14/42), 23.7% (45/190) and 17.4% (8/46) of the reports bleeding events related to SSRIs and anticoagulants, SSRIs and platelet aggregation inhibitors and SSRIs and NSAIDs were reported. Hyponatremia was reported in 7.6% (22/289) of the reports related to antidepressants and diuretics and increased beta-blocker effects in 6.9% (8/116) of the reports related to SSRIs and beta-blockers.ConclusionsAccording to our analysis, well-known DDI still occur in the treatment of psychiatric patients with psychiatric drugs and somatic medication. Whenever possible, alternative drug combinations with a lower potential of DDIs may be considered or appropriate monitoring measures should be conducted.Disclosure of InterestNone Declared

Improving the Sexual Wellbeing of Patients with Psychotic Illness

Introduction Sexual dysfunction (SD) is common in psychotic illness including schizophrenia, occurring in 30-82% of patients. It negatively impacts wellbeing and antipsychotic compliance, resulting in higher risk of relapse and hospitalisation. Due to over-reliance on spontaneous reports from patients, SD is typically under-identified which prevents investigation and treatment.ObjectivesTo establish whether SD is under-identified in patients with psychosis in a general adult community mental health team; to elicit whether the Arizona Sexual Experience Scale (ASEX) improves identification; to investigate and manage identified cases of SD; to make recommendations about identification and monitoring of SD in this patient population.MethodsA 12-month retrospective audit of patients with psychosis prescribed a long-acting injectable (LAI) antipsychotic (n=36) to identify sexual symptoms was completed. The ASEX was subsequently issued to screen for SD.ResultsAudit: 3/36 (8%) patients had documented sexual symptoms. Of the 18/36 patients that completed the ASEX: 10 (56%) exhibited SD. 4 consented to further investigation. 5 patients experienced significant difficulties with the language used in the ASEX. At the end of the project we revised the ASEX with simpler, colloquial language.ConclusionsImplementation of the ASEX results in clear improvements in identification and monitoring of SD. Maudsley Practice Guidelines can inform investigation and management of SD. We suggest a review of NICE guidance to incorporate the above into clinical practice. Further work is needed to establish whether the revised ASEX can be developed and validated.Disclosure of InterestNone Declared

An Overview of Pharmacovigilance Practice and Management in Sub-Saharan African Countries

Most sub-Sahara African countries faced with prolonged resource deficiencies suffers specific constraints in establishing a functional and operationally-free pharmacovigilance systems platforms which should guide and in facilitate the generation of vital data to reinforce health information policies and practices. Despite the commendable efforts invested by the different stake holders within such countries to harmonize pharmacovigilance guidelines and regulations, lack of integration and the dependence on pharmacovigilance systems remain major constrains. Other identified difficulties are those associated with the problem of translating data reporting tools into multiple communicable languages, and the inadequacy of the healthcare experts who translates with the patient’s population, the pressure imposed by the short consultation time between a patient and a health practitioner. To add to this, there exist issues of community concern like the increasing use of herbal traditional products with anecdotal therapeutic evidence, low quality, self-medication practices, counterfeit and roadside drugs use, substandard medications that are readily accessible to the population. Some prolonged problems are associated with social and political instability, territorial conflicts, little or no access to drug utilization data, which makes it difficult to reliably estimate the true risks of medication use. Pharmacovigilance activities are still at its infancy due to poor and less trained health personnel, lack of budget allocation for health vigilance from the State financial attributions. In addition to the limited investment in pharmacovigilance activities, there is little collaboration between public health programmes and National Medicines Regulatory Authorities (NMRA), especially during mass drug administration for neglected tropical diseases and mass vaccinations. Frequent spontaneous report in SSA is low and this can hinder robust signal detection analyses. This paper attempts to identify the challenges of the practice of pharmacovigilance in sub-Saharan African countries and its implication in health vigilance in the community. In this paper, we review the specific challenges and areas of progress in pharmacovigilance in SSA.

Customizing the human-avatar mapping based on EEG error related potentials

Objective. A key challenge of virtual reality (VR) applications is to maintain a reliable human-avatar mapping. Users may lose the sense of controlling (sense of agency), owning (sense of body ownership), or being located (sense of self-location) inside the virtual body when they perceive erroneous interaction, i.e. a break-in-embodiment (BiE). However, the way to detect such an inadequate event is currently limited to questionnaires or spontaneous reports from users. The ability to implicitly detect BiE in real-time enables us to adjust human-avatar mapping without interruption. Approach. We propose and empirically demonstrate a novel brain computer interface (BCI) approach that monitors the occurrence of BiE based on the users’ brain oscillatory activity in real-time to adjust the human-avatar mapping in VR. We collected EEG activity of 37 participants while they performed reaching movements with their avatar with different magnitude of distortion. Main results. Our BCI approach seamlessly predicts occurrence of BiE in varying magnitude of erroneous interaction. The mapping has been customized by BCI-reinforcement learning (RL) closed-loop system to prevent BiE from occurring. Furthermore, a non-personalized BCI decoder generalizes to new users, enabling ‘Plug-and-Play’ ErrP-based non-invasive BCI. The proposed VR system allows customization of human-avatar mapping without personalized BCI decoders or spontaneous reports. Significance. We anticipate that our newly developed VR-BCI can be useful to maintain an engaging avatar-based interaction and a compelling immersive experience while detecting when users notice a problem and seamlessly correcting it.

Detection of iodixanol-induced allergic reaction signals in Chinese inpatients: a multi-center retrospective database study using prescription sequence symmetry analysis.

This study aimed to explore the signal detection method for allergic reactions induced by inpatient iodixanol injection. A database of 3,719,217 hospitalized patients from 20 large Chinese general hospitals was processed and analyzed using the prescription sequence symmetry analysis (PSSA) method. 126,680 inpatients who used iodixanol and were concurrently treated with anti-allergic drugs were analyzed. In the medical records of these patients, only 32 had documented iodixanol allergies. Statistical analysis identified 22 drugs in 4 categories-calcium preparations, adrenergic/dopaminergic agents, glucocorticoids, and antihistamines-as marker drugs. With time intervals of 3, 7, and 28days, the adjusted sequence ratios (aSRs) for all anti-allergics and the 4 categories were greater than 1. The 7-day aSRs were 2.12 (95% CI: 2.08-2.15), 1.70 (95% CI: 1.68-1.73), 3.85 (95% confidence interval [CI]: 3.75-2.30), 2.30 (95% CI: 2.26-2.35), and 1.95 (95% CI: 1.89-2.02), respectively. The proportions of adverse drug events indicated by each signal were as follows: all anti-allergics (2.92%-3%), calcium gluconate (0.19%-0.52%), adrenergic/dopaminergic agents (2.20%-3.37%), glucocorticoids (3.13%-3.76%), and antihistamines (1.05%-1.32%). This first multi-center Chinese inpatient database study detected iodixanol-induced allergy signals, revealing that reactions may be much higher than those in collected spontaneous reports. Iodixanol risk exposure was closer to actual pharmaceutical care findings. PSSA application with ≤7-day intervals appears better suited for monitoring late allergic reaction signals with these drugs.

Analysis and Reporting of Adverse Drug Reactions of Cosmetics at a Tertiary Care Hospital.

Background and objectives Cosmetovigilance is a term used for the activities related to the collection, evaluation, and monitoring of spontaneous reports of undesirable events observed during or after normal or reasonably foreseeable use of a cosmetic product. It is now considered a part of the public health system to determine the toxicity of cosmetic products. India has a pharmacovigilance system that monitors adverse drug reactions. Adverse effects due to the use of cosmetic products are undernumbered and a rigorous vigilant system is necessary to check the unmet needs of our country. Hence keeping the above in view, the study was conducted. Material and methods Patients of any gender, aged above 18 years, reporting adverse reactions to cosmetics at the study site were included in the study. The adverse reactions to cosmetics were noted. The causality of the observed adverse cosmetic reactions (ACRs) wasdone by the European Cosmetic, Toiletry and Perfumery Association (COLIPA) and Product Lifecycle Management (PLM) methods. Results A total of 120 patients were included in the study. The cosmetic products used by the patients were mainly face care products (n=144) followed by make-up care products (n=126). A total of 121 types of ACRs were reported. The majority of the ACRs were caused by products involved in facial care (62; 51.2%) followed by personal care products (20; 16.5%). In the causality assessment of the ACRs using the COLIPA method, 49.4% of patients were categorized as likely, and using the PLM method, 59% of the events were categorized as probable. Conclusion Most of the ACRs were caused by face care products and acne was reported as the most frequently occurring ACR. Awareness programs regarding the reporting of ACRs should be encouraged among cosmetic users and stakeholders.

Electrolyte disorders induced by six multikinase inhibitors therapy for renal cell carcinoma: a large-scale pharmacovigilance analysis

To provide evidence for optimization of multi-kinase inhibitors (MKIs) use in the clinic, we use the public database to describe and evaluate electrolyte disorders (EDs) related to various MKIs treated for renal cell carcinoma. We analyzed spontaneous reports submitted to the Food and Drug Administration Adverse Events Reporting System (FAERS) in an observational and retrospective manner. Selecting electrolyte disorders' adverse events to multikinase inhibitors (axitinib, cabozantinib, lenvatinib, pazopanib, sunitinib, and sorafenib). We used Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) algorithms to analyze suspected adverse reactions of electrolyte disorders induced by MKIs (which were treated for renal cell carcinoma) between January 2004 and December 2022. As of December 2022, 2772 MKIs (which were treated for renal cell carcinoma) ICSRs were related to electrolyte disorders AEs. In general, there were more AEs cases in males, except lenvatinib and 71.8% of the cases were submitted from North America. ICSRs in this study, the age group most frequently affected by electrolyte disorders AEs was individuals aged 45–64 years for axitinib, cabozantinib, pazopanib, and sunitinib, whereas electrolyte disorders AEs were more common in older patients (65–74 years) for sorafenib and lenvatinib. For all EDs documented in ICSRs (excluding missing data), the most common adverse outcome was hospitalization(1429/2674, 53.4%), and the most serious outcome was death/life-threat(281/2674, 10.5%). The prevalence of mortality was highest for sunitinib-related EDs (145/616, 23.5%), excluding missing data (n = 68), followed by cabozantinib-related EDs (20/237, 8.4%), excluding missing data (n = 1). The distribution of time-to-onset of Each drug-related ICSRs was not all the same, and the difference was statistically significant (P = 0.001). With the criteria of ROR, the six MKIs were all significantly associated with electrolyte disorders AEs, the strongest association was the association between cabozantinib and hypermagnesaemia. MKIs have been reported to have significant electrolyte disorders AEs. Patients and physicians need to recognize and monitor these potentially fatal adverse events.

The Impact of the COVID-19 Pandemic on the Incidence of Herpes Zoster: A Narrative Literature Review.

Coronavirus disease 2019 (COVID-19) has had a broad impact on health services and health outcomes. During the pandemic, there were numerous reports of herpes zoster (HZ) in people with COVID-19 and in COVID-19 vaccine recipients. The aim of this review is to elucidate the global effects of the COVID-19 pandemic on HZ. It is postulated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection produces an immunosuppressive state that favours varicella zoster virus (VZV) reactivation. Three large cohort studies (a multinational study and studies from the USA and Spain) that excluded individuals vaccinated against HZ reported significantly increased risk of HZ following COVID-19 infection, especially in people aged ≥ 50years. In contrast, a large study from Israel that did not consider HZ vaccination status reported no such increase. Cases of HZ following COVID-19 vaccination have been reported and may be the result of attenuated cell-mediated immunity. This phenomenon appears to vary by vaccine type. Some (but not all) large analyses have reported a significant positive relationship between receipt of mRNA vaccines for COVID-19 and development of HZ. These include analyses of health records databases in Israel and Hong Kong and of spontaneous case reports in the US Vaccine Adverse Event Reporting System (VAERS) database. Routine vaccinations, including shingles vaccine programmes, were disrupted by the COVID-19 pandemic. It is estimated that missed shingles vaccinations may have resulted in 63,117 avoidable HZ cases in the USA. Now that the World Health Organization has declared an end to the COVID-19 pandemic as a health emergency and routine vaccination services have resumed, there is a need to increase awareness of HZ and HZ vaccination.Graphical abstract available for this article.

Statistical Methodologies for Detecting Drug-Drug Interaction Using Spontaneous Reporting System

Statistical methodologies of signal detection for drug-drug interactions (DDIs) have been developed and used. In this study, we review methodologies for DDI signal detection using the spontaneous reporting system. We describe the characteristics of the additive and multiplicative risk model, logistic regression model, Multi-item Gamma-Poisson Shrinker, <i>Ω</i> shrinkage measure model, and Chi-square statistics model. We discuss the advantages and disadvantages of each methodology along with examples, providing researchers with information to choose the most appropriate methodology for their study.

The Role of the European Medicines Agency in the Safety Monitoring of COVID-19 Vaccines and Future Directions in Enhancing Vaccine Safety Globally.

The European Union (EU) regulatory network was at the forefront of the safety monitoring of COVID-19 vaccines during the pandemic. An unprecedented number of case reports of suspected adverse reactions after vaccination called for huge efforts for the assessment of this safety information, to ensure that any possible risks were detected and managed as early as possible, while ruling out coincidental but temporally related adverse health outcomes. We describe the role of the European Medicines Agency alongside the EU regulatory network in the safety monitoring of the COVID-19 vaccines, and provide an insight into challenges, particularities and outcomes of the scientific assessment and regulatory decisions in the complex, dynamic international environment of the pandemic. We discuss the flexible procedural tools that were used to ensure an expedited scientific assessment of safety issues, and subsequent updates of the product information (i.e., labelling) when available evidence (e.g., spontaneous reports, findings from observational studies and/or scientific literature) suggested that causal association is at least a reasonable possibility. The safety monitoring was accompanied by enhanced transparency measures, proactive communication, and easy access to information, which played a key role in public reassurance. The pandemic has been a powerful booster for worldwide collaboration, exchange of information and work-sharing. The safety monitoring of COVID-19 vaccines continues, and the lessons learned will be applied in future safety reviews, as well as future health emergencies.

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.

Audiovestibular adverse events following COVID-19 vaccinations

IntroductionEvidence regarding audiovestibular adverse events post COVID-19 vaccination to date has been inconclusive regarding a potential association. This study aimed to determine if there was an increase in audiovestibular events following COVID-19 vaccination in South-eastern Australia during January 2021–March 2023. MethodsA multi-data source approach was applied. First, a retrospective observational analysis of spontaneous reports of audiovestibular events to a statewide vaccine safety surveillance service, SAEFVIC. Second, a self-controlled case series analysis using general practice data collected via the POpulation Level Analysis and Reporting (POLAR) tool. Results and conclusionsThis study is the first to demonstrate an increase in general practice presentations of vertigo following mRNA vaccines (RI = 1.40, P <.001), and tinnitus following both the Vaxzevria® adenovirus vector and mRNA vaccines (RI = 2.25, P <.001 and 1.53, P <.001 respectively). There was no increase in hearing loss following any COVID-19 vaccinations. Our study, however, was unable to account for the potential of concurrent COVID-19 infections, which literature has indicated to be associated with audiovestibular events.Healthcare providers and vaccinees should be alert to potential audiovestibular complaints after COVID-19 vaccination. Our analysis highlights the importance of using large real-world datasets to gather reliable evidence for public health decision making.

A Natural Language Processing Framework for Detecting Adverse Drug Reactions in Clinical Structured Drug Reviews

Background: Adverse drug reactions (ADRs) pose significant concerns in healthcare, yet their underreporting remains a challenge. Extracting spontaneous and non-automatic reports from free-text narratives contributes to this low rate of reporting. An automatic ADR detection system can mitigate these issues by identifying, summarizing, and reporting ADRs in a document. This study presents an adverse drug reaction detector (ADRD), a natural language processing (NLP) framework applied to the psychiatric treatment adverse reactions (PsyTAR) dataset. Aiming to automate ADR analysis, the framework explores the relationship between ADRs and patient satisfaction. Methods: A comprehensive eight-phase approach was employed in the ADRD framework, utilizing Python programming language libraries and NLP tools. The dataset underwent meticulous preprocessing, and the subsequent phases involved data summarization, pattern identification, data cleaning, sentiment calculation, assessment of drug effectiveness and usefulness, analysis of medical conditions, and identification of the most effective and ineffective drugs for each condition. Results: Analyzing 891 comments related to four unique drugs (i.e., Zoloft, Lexapro, Cymbalta, and Effexor XR) from patients with 285 distinct conditions, the framework offered insights into the dataset structure, statistical indicators, distribution of ratings and ADR counts, the impact of ratings on ADR counts, and length of comments’ influence on ratings. Conclusion: The challenges of extracting ADR reports from free-text narratives have led to their underreporting. ADRD offers an automated and insightful approach for enhancing ADR analysis and reporting processes, making strides toward bridging the gap in ADR reporting.