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Background: Older adults are at a higher risk of severe adverse drug events (ADEs) because of multimorbidity, polypharmacy, and lower physiological function. This study aimed to determine whether polypharmacy, defined as the use of ≥ 5 active drug ingredients, was associated with severe ADEs in this population., Methods: We used ADE reports from the Korea Institute of Drug Safety and Risk Management-Korea Adverse Event Reporting System Database, a national spontaneous ADE report system, from 2012 to 2021 to examine and compare the strength of association between polypharmacy and severe ADEs in older adults (≥ 65 years) and younger adults (20-64 years) using disproportionality analysis., Results: We found a significant association between severe ADEs of cardiac and renal/urinary Medical Dictionary for Regulatory Activities System Organ Classes (MedDRA SOC) with polypharmacy in older adults. Regarding individual-level ADEs included in these MedDRA SOCs, acute cardiac arrest and renal failure were more significantly associated with polypharmacy in older adults compared with younger adults., Conclusion: The addition of new drugs to the regimens of older adults warrants close monitoring of renal and cardiac symptoms., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Post-marketing pharmacosurveillance is important to reduce harm to patients from marketed drugs. Oral adverse drug reactions (OADRs) are seldom reported and only few OADRs are listed scarcely in summary of product characteristics (SmPC) of drugs., Objective: Structured search for OADRs in the Danish Medicines Agencies database from January 2009 to July 2019., Results: Forty-eight percent of OADRs were categorized as "serious" where oro-facial swelling was reported 1041 times, medication-related osteonecrosis of the jaw (MRONJ) 607 times and para- or hypoaesthesia 329 times. Four-hundred-eighty OADRs in 343 cases were related to biologic or biosimilar drugs where 73% affected the jawbone as MRONJ. Physician reported 44%, dentists 19% and citizens 10% of OADRs., Conclusions: Health care professionals had a sporadic reporting pattern that seemed to be influenced by the debate in the community and in professional circles but also by the information in the SmPC of the drugs. The results indicate some reporting stimulation of OADRs in relation to Gardasil 4, Septanest, Eltroxin and MRONJ. Eventually the knowledge of OADRs increases but there is a risk of skewed information if reporting is not systematic, reliable and consistent. All healthcare professionals must be educated in spotting and reporting all suspected adverse drug reactions., (© 2023 Wiley Periodicals LLC.)

Aims: Adverse drug reactions (ADRs) are known to show sex-specific differences in occurrence and phenotype. The aim of this study was to analyse sex-specific differences in ADR-drug combinations that required hospitalization based on two different datasets., Methods: We performed a complementary analysis of (i) spontaneously reported (n = 12 564, female = 51.7%) and (ii) systematically collected ADR reports from a prospective multicentre observational study (ADRED, n = 2355, female = 48.2%) from Germany in the ADR database EudraVigilance (EV). Both datasets were analysed separately concerning the suspected drugs, ADRs and ADR-drug combinations more frequently reported for females or males by calculating reporting odds ratios (ROR) with 95% confidence intervals. ADR-drug combinations more frequently reported for either females or males in EV reports were related to prescription data. Finally, the results from both datasets were discussed with regard to their (dis-)concordance., Results: In both datasets, some antineoplastic agents and nervous system drugs were found to be reported more often for females than males (RORs ranging from 1.5 [1.1-2.1] for quetiapine in spontaneous reports to 41.3 [13.1-130.0] for trastuzumab in spontaneous reports). ADRs of the respiratory system, and haemorrhages were described predominantly for males in both datasets. In spontaneous reports the ADR-drug combination self-injurious behaviour-quetiapine was more often reported for females without and with consideration of drug prescriptions (ROR: 3.8 [1.3-11.0]). Quetiapine and psychiatric disorders (superordinate level) was exclusively reported for females in ADRED reports., Conclusions: Our results can contribute to raise awareness and further knowledge regarding sex-specific ADRs. The findings require further in-depth investigation., (© 2023 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

In recent years, complications of drug therapy are an important medical problem. Data on adverse drug reactions (ADR) in patients of older age groups were analyzed. The object of the study was notification cards for unwanted reactions received from medical organizations of the Irkutsk region for period 2009-2020 years. The Narangio scale was used to assess the causality between ADR and medicines. Of the 1021 ADR notifications in patients over 65 years of age, 2/3 (668) are presented with ADR notifications in women, 353 (34,6%) in men. The presence of background diseases was registered in 915 notifications (89,6%). There were no gender differences except for a higher incidence of chronic obstructive pulmonary disease in men (7,2 and 3,5% respectively, p<0,05) and diabetes mellitus in women (14 and 3,5% respectively, p<0,05). ADRs for antibacterial agents amounted to 31,8%, drugs for the treatment of cardiovascular diseases - 10,5%, cases of therapeutic inefficiency - 5,1%. The ADR data statement was in line with the recommended form of 76%. The most common filling defect was incomplete patient information. The validity of the Narango causation was high. The deadlines for reporting data were observed in 89,1%. For effective interaction in the pharmacovigilance system, it is necessary in each medical organization to constantly inform about the procedure for pharmacovigilance, types of ADRs, the rules for their detection and the timing of data reporting. The work should be supervised by a trained specialist.

Purpose: Literature reports of adverse drug events can be replicated across multiple companies, resulting in extreme duplication (defined as a majority of reports being duplicates) in the FDA Adverse Event Reporting System (FAERS) database because they can escape legacy duplicate detection algorithms routinely deployed on that data source. Literature reference field, added to in 2014, could potentially be utilized to identify replicated reports. FAERS does not enforce adherence to the Vancouver referencing convention, thus the same article may be referenced differently leading to duplication. The objective of this analysis is to determine if variations of the same literature references observed in FAERS can be resolved with text normalization and fuzzy string matching., Methods: We normalized the literature references recorded in the FAERS database through the first quarter of 2021 with a rule-based algorithm so that they better conform to the Vancouver convention. Levenshtein distance was then utilized to merge sufficiently similar normalized literature references together., Results: Normalization of literature references increases the percentage that can be parsed into author, title, and journal from 61.74% to 93.93%. We observe that about 98% of pairs within groups do have a Levenshtein similarity of the title above the threshold. The extreme duplication ranged from 66% to 87% with a median of 72% of reports being duplicates and often involved addictovigilance scenarios., Conclusions: We have shown that these normalized references can be merged via fuzzy string matching to improve enumeration of all the individual case safety reports that refer to the same article. Inclusion of the PubMed ID and adherence to the Vancouver convention could facilitate identification of duplicates in the FAERS dataset. Awareness of this phenomenon may improve disproportionality analysis, especially in areas such as addictovigilance., (© 2022 John Wiley & Sons Ltd.)

Purpose: This study aimed to identify factors that influence the decision to take safety regulatory actions in routine signal management based on spontaneous reports. For this purpose, we analyzed the safety signals identified from the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and related information., Method: From the signals that the FDA identified in the FAERS between 2008 1Q and 2014 4Q, we selected 216 signals for which regulatory action was or was not taken. Characteristics of the signals were extracted from the FAERS quarterly reports that give information about what signals were identified from the FAERS and what actions were taken for them, and the FAERS data released in the same quarter when the signal was published. Univariate and multivariable logistic regression analysis was used to assess the relationship between the characteristics of each of the signals and the decision on regulatory action., Result: As a result of the univariate logistic regression analysis, we selected 5 factors (positive rechallenge, number of cases accumulated in the last one-year period before the signal indication, previous awareness, serious outcome, risk for special populations) to include in the multivariable logistic regression model (p < 0.2). The multivariate logistic regression analysis showed that the number of cases accumulated in the last one-year period before the signal indication and previous awareness were associated with the regulatory action (p < 0.05)., Conclusion: The present study showed that number of cases accumulated in the last one-year period before the signal indication and previous awareness potentially associated with the United States regulatory action. When assessing safety signals, we should be careful of the adverse events with a large number of cases accumulated rapidly in a short period. In addition, we should pay attention to new information on not only unknown risks but also previously identified and potential risks.

Background : In Singapore, the Health Sciences Authority (HSA) reviews an average of 20,000 spontaneous adverse event (AE) reports yearly. Potential safety signals are identified manually and discussed on a weekly basis. In this study, we compared the use of four quantitative data mining (QDM) methods with weekly manual review to determine if signals of disproportionate reporting (SDRs) can improve the efficiency of manual reviews and thereby enhance drug safety signal detection. Methods : We formulated a QDM triage strategy to reduce the number of SDRs for weekly review and compared the results against those derived from manual reviews alone for the same 6-month period. We then incorporated QDM triage into the manual review workflow for the subsequent two 6-month periods and made further comparisons against QDM triage alone. Results : The incorporation of QDM triage into routine manual reviews resulted in a reduction of 20% to 30% in the number of drug-AE pairs identified for further evaluation. Sequential Probability Ratio Test (SPRT) detected more signals that mirror human manual signal detection than the other three methods. Conclusions : The adoption of QDM triage into our manual reviews is a more efficient way forward in signal detection, avoiding missing important drug safety signals.

Introduction: In France since 2011, report of adverse drug reactions (ADRs) has been extended to patients (and patients' associations) who can declare directly ADRs to their regional pharmacovigilance centre. In pharmacovigilance, informativeness of ADRs reports is important to improve signal's detection. The present study was performed to compare the quality of patients', physicians and community pharmacists' reports., Methods: We performed a retrospective study investigating the quality of patients', physicians and community pharmacies' ADRs reported to Toulouse University PharmacoVigilance Centre (TUPVC) from January 2014 to June 2017. We used mandatory and non-mandatory criteria, as defined by European Medicines Agency. Reports' quality was defined as "satisfactory" when more than 90% of items were completed. We also compared reports' quality according to ADRs seriousness and the used reporting tools (email or the mobile app VigiBip ® )., Results: The number of reports to TUPVC increased between 2014 and 2016 (+51%) for patients and remained stable for pharmacists and physicians. According to the mandatory criteria, quality of the investigated reports was "satisfactory" (more than 90% of the items filled) whatever the reporter and without significant differences between reporters. For the non-mandatory criteria, clinical description of ADRs and ADRs' outcome were only filled over 90%. Significant differences were observed between the different reporters: community pharmacists informed better clinical description, ADR outcome and concomitant drugs versus both patients and physicians. Physicians informed better medical history and biological data whereas patients informed medical history and other aetiologies better than pharmacists and clinical description of ADRs better than physicians., Conclusion: The present study failed to show differences between pharmacies', physicians' and patients' ADRs reports, for the mandatory criteria. However, significant differences were found for non-mandatory criteria with drug data more filled by pharmacists and medical ones more by physicians and patients., (Copyright © 2019 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.)

Purpose: The main objective of this study was to analyze validated cases of drug-induced anaphylactic reactions in children with regard to incriminated drugs, clinical characteristics, and associated factors. A further objective was to compare differences in incriminated drugs and characteristics between validated cases and a reference excluding anaphylactic reaction cases (basic dataset)., Methods: Spontaneous reports of anaphylactic reactions in children (0-17 years) registered between January 2000 to December 2016 were extracted from the adverse drug reaction database of the German Federal Institute for Drugs and Medical Devices. These reports were restricted to drugs for which at least four cases were found. After case validation, 159 reports remained (validated dataset) and were compared with the basic dataset (n = 12.168 reports) using inferential statistics., Results: Estimated yearly increase of reports (36.8 vs 0.1), most frequently incriminated drugs (antibiotics 30.2% vs 11%, analgesics/antipyretics 22.0% vs 5.6%; P values less than 0.001) and route of administration (38.4% vs 6.7%) differed between the validated dataset and the basic dataset. Validated cases differed in severity (higher with atracurium), reported symptoms (urticaria leading with analgesics), and associated factors (atopy/allergy rarely reported with antibiotics) depending on the incriminated drug class. In 13.8% (11.3% if excluding repeated readministration in one person) of the cases, the drug had not been tolerated before., Conclusions: A heterogeneous clinical phenotype with differences in associated factors was observed, suggesting different underlying mechanisms triggered by the different drug groups. Occurrence of serious drug-induced anaphylactic reactions in children could be reduced by carefully considering patient history., (© 2019 The Authors Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd.)

Purpose: Data mining has been introduced as one of the most useful methods for signal detection by spontaneous reports, but data mining is not always effective in detecting all safety issues. To investigate appropriate situations in which data mining is effective in routine signal detection activities, we analyzed the characteristics of signals that the US Food and Drug Administration (FDA) identified from the FDA Adverse Event Reporting System (FAERS)., Methods: Among the signals that the FDA identified from the FAERS between 2008 1Q and 2014 4Q, we selected 233 signals to evaluate in this study. We conducted a disproportionality analysis and classified these signals into two groups according to the presence or absence of statistical significance in the reporting odds ratio (ROR). Then, we compared the two groups based on the characteristics of the suspected drugs and adverse events (AEs)., Results: Safety signals were most frequently identified for new drugs that had been on the market for less than 5 years, but some signals were still identified for old drugs (≥20 years), and most of them were statistically significant. The proportion of the signals for "serious" events was significantly higher in the group of nonsignals by ROR (Fisher's exact test, P = 0.032)., Conclusions: Data mining was shown to be effective in the following situations: (1) early detection of safety issues for newly marketed drugs, (2) continuous monitoring of safety issues for old drugs, and (3) signal detection of nonserious AEs, to which little attention is usually given., (© 2018 John Wiley & Sons, Ltd.)

Purpose: vigiRank is a data-driven predictive model for emerging safety signals. In addition to disproportionate reporting patterns, it also accounts for the completeness, recency, and geographic spread of individual case reporting, as well as the availability of case narratives. Previous retrospective analysis suggested that vigiRank performed better than disproportionality analysis alone. The purpose of the present analysis was to evaluate its prospective performance., Methods: The evaluation of vigiRank was based on real-world signal detection in VigiBase. In May 2014, vigiRank scores were computed for pairs of new drugs and WHO Adverse Reaction Terminology critical terms with at most 30 reports from at least 2 countries. Initial manual assessments were performed in order of descending score, selecting a subset of drug-adverse drug reaction pairs for in-depth expert assessment. The primary performance metric was the proportion of initial assessments that were decided signals during in-depth assessment. As comparator, the historical performance for disproportionality- guided signal detection in VigiBase was computed from a corresponding cohort of drug-adverse drug reaction pairs assessed between 2009 and 2013. During this period, the requirement for initial manual assessment was a positive lower endpoint of the 95% credibility interval of the Information Component measure of disproportionality, observed for the first time., Results: 194 initial assessments suggested by vigiRank's ordering eventually resulted in 6 (3.1%) signals. Disproportionality analysis yielded 19 signals from 1592 initial assessments (1.2%; P < .05)., Conclusions: Combining multiple strength-of-evidence aspects as in vigiRank significantly outperformed disproportionality analysis alone in real-world pharmacovigilance signal detection, for VigiBase., (© 2017 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd.)

Background and Objective: The availability of accurate product-specific exposure information is essential in the pharmacovigilance of biologicals, because differences in the safety profile may emerge between products containing the same active substance. In spontaneous adverse drug reaction (ADR) reports, drug exposure may, however, be misclassified, that is, attributed to the incorrect product. The aim of this study was to explore the effect of exposure misclassification on the time to detection of product-specific risks in spontaneous reporting systems., Methods: We used data simulations to explore the effect of exposure misclassification. We simulated an active substance-specific subset of a spontaneous reporting system and used the proportional reporting ratio for signal detection. The effect of exposure misclassification was evaluated in three test cases representing product-specific ADRs that may occur for biologicals and studied in relative terms by varying the model parameters (market share and relative risk)., Results: We found that exposure misclassification results in the largest delay in identification of risks that have a weak association (relative risk < 2 or 3) with the product of interest and in situations where the product associated with the unique risk has a large (>50%) market share. The absolute public health impact of exposure misclassification, in terms of cases/time to detection, varied considerably across the test cases., Conclusion: Exposure misclassification in ADR reports may result in a delayed detection of product-specific risks, particularly in the detection of weak drug-event associations. Our findings can help inform the future implementation and refinement of product-specific and batch-specific signal detection procedures., (Copyright © 2015 John Wiley & Sons, Ltd.)

Antibacterial drugs are a widely used drug class due to the frequency of infectious diseases globally. Risks knowledge should ground these medicines' selection. Data mining in large databases is essential to identify early safety signals and to support pharmacovigilance systems. We conducted a cross-sectional study to assess adverse drug events related to antibiotics reporting between December 2018 and December 2021 in the Brazilian database (Vigimed/VigiFlow). We used the Reporting Odds Ratio (ROR) disproportionality analysis method to identify disproportionate reporting signals (SDR), referring to statistical combinations between drugs and adverse events. Vancomycin was the most reported antibiotic (n = 1,733), followed by ceftriaxone (n = 1,277) and piperacillin and tazobactam (n = 1,024). We detected 294 safety signals related to antibacterials. We identified azithromycin leading in the number of safety signals (n = 49), followed by polymyxin B (n = 25). Of these, 95 were not provided for in the drug label and had little or no reports in the medical literature. Three serious events are associated with ceftazidime and avibactam, a new drug in the Brazilian market. We also found suicide attempts as a sign associated with amoxicillin/clavulanate. Gait disturbance, a worrying event, especially in the elderly, was associated with azithromycin. Our findings may help guide further pharmacoepidemiologic studies and monitoring safety signals in pharmacovigilance. [ABSTRACT FROM AUTHOR]

Antibacterial drugs are a widely used drug class due to the frequency of infectious diseases globally. Risks knowledge should ground these medicines’ selection. Data mining in large databases is essential to identify early safety signals and to support pharmacovigilance systems. We conducted a cross-sectional study to assess adverse drug events related to antibiotics reporting between December 2018 and December 2021 in the Brazilian database (Vigimed/VigiFlow). We used the Reporting Odds Ratio (ROR) disproportionality analysis method to identify disproportionate reporting signals (SDR), referring to statistical combinations between drugs and adverse events. Vancomycin was the most reported antibiotic (n = 1,733), followed by ceftriaxone (n = 1,277) and piperacillin and tazobactam (n = 1,024). We detected 294 safety signals related to antibacterials. We identified azithromycin leading in the number of safety signals (n = 49), followed by polymyxin B (n = 25). Of these, 95 were not provided for in the drug label and had little or no reports in the medical literature. Three serious events are associated with ceftazidime and avibactam, a new drug in the Brazilian market. We also found suicide attempts as a sign associated with amoxicillin/clavulanate. Gait disturbance, a worrying event, especially in the elderly, was associated with azithromycin. Our findings may help guide further pharmacoepidemiologic studies and monitoring safety signals in pharmacovigilance.