The Irony of MedWatch and the FAERS Database: An Assessment of Data Input Errors and Potential Consequences
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ABSTRACT:
SUBMITTER: Veronin M
PROVIDER: S-EPMC7359666 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: Not available
| S-EPMC10978795 | biostudies-literature
Project description:Objective: The introduction of Bruton's tyrosine kinase (BTK) inhibitors was a milestone in the treatment of B-cell malignancies in recent years owing to its desired efficacy against chronic lymphocytic leukaemia and small cell lymphocytic lymphoma. However, safety issues have hindered its application in clinical practice. The current study aimed to explore the safety warning signals of BTK inhibitors in a real-world setting using the FDA Adverse Event Reporting System (FAERS) to provide reference for clinical rational drug use. Methods: Owing to the short marketing time of other drugs (zanbrutinib and orelabrutinib), we only analysed ibrutinib and acalabrutinib in this study. All data were obtained from the FAERS database from January 2004 to December 2021. Disproportionality analysis and Bayesian analysis were utilised to detect and assess the adverse event (AE) signals of BTK inhibitors. Results: In total, 43,429 reports of ibrutinib were extracted and 1527 AEs were identified, whereas 1742 reports of acalabrutinib were extracted and 220 AEs were identified by disproportionality analysis and Bayesian analysis. Among reports, males were more prone to develop AEs (58.2% for males vs. 35.6% for females treated with ibrutinib, and 55.9% vs. 31.9%, respectively, for acalabrutinib), and more than 30% of patients that suffered from AEs were over 65 years of age. Subsequently, we investigated the top 20 preferred terms (PTs) associated with the signal strength of ibrutinib and acalabrutinib, and our results identified 25 (13 vs. 12, respectively) novel risk signals. Among the top 20 PTs related to death reports, the terms infectious, pneumonia, pleural effusion, fall, asthenia, diarrhoea, and fatigue were all ranked high for these two BTK inhibitors. Further, cardiac disorders were also an important cause of death with ibrutinib. Conclusion: Patients treated with ibrutinib were more prone to develop AEs than those treated with acalabrutinib. Importantly, infection-related adverse reactions, such as pneumonia and pleural effusion, were the most common risk signals related to high mortality associated with both BTK inhibitors, especially in elderly patients. Moreover, cardiovascular-related adverse reactions, such as atrial fibrillation and cardiac failure, were fatal AEs associated with ibrutinib. Our results provide a rationale for physicians to choose suitable BTK inhibitors for different patients and provide appropriate monitoring to achieve safer therapy and longer survival.
| S-EPMC9691840 | biostudies-literature
Project description:In this study, we used the large number of cases in the FDA adverse-event reporting system (FAERS) database to investigate risk factors for drug-induced hiccups and to explore the relationship between hiccups and gender. From 11,810,863 adverse drug reactions reported between the first quarter of 2004 and the first quarter of 2020, we extracted only those in which side effects occurred between the beginning and end of drug administration. Our sample included 1454 adverse reactions for hiccups, with 1159 involving males and 257 involving females (the gender in 38 reports was unknown). We performed univariate analyses of the presence or absence of hiccups for each drug and performed multivariate analysis by adding patient information. The multivariate analysis showed nicotine products to be key suspect drugs for both men and women. For males, the risk factors for hiccups included older age, lower body weight, nicotine, and 14 other drugs. For females, only nicotine and three other drugs were extracted as independent risk factors. Using FAERS, we were thus able to extract new suspect drugs for drug-induced hiccups. Furthermore, this is the first report of a gender-specific analysis of risk factors for hiccups that provides novel insights into drug-induced hiccups, and it suggests that the mechanism responsible is strongly related to gender. Thus, this study can contribute to elucidating the mechanism underlying this phenomenon.
| S-EPMC8780603 | biostudies-literature
Project description:PurposeThis study aims to comprehensively assess the safety of Asenapine by conducting an comprehensive statistical analysis of adverse event reports in the FAERS database, with a particular focus on potential adverse reactions related to its use in the treatment of psychiatric disorders.MethodsEvent reports from the first quarter of 2009 to the third quarter of 2023 were collected and analyzed. Detailed examinations of gender, age, reporter identity, and other aspects were conducted to reveal the fundamental characteristics of Asenapine-related adverse events. Signal mining techniques were employed to systematically evaluate various adverse reactions associated with Asenapine.ResultsThe study found that adverse event reports involving Asenapine were more common among female patients, with the age group mainly distributed between 18 and 45 years. Physicians were the primary reporters of adverse events, and psychiatric disorders, neurological disorders, and gastrointestinal disorders were the most common areas affected by adverse reactions. In addition to known adverse reactions, potential risks not mentioned in the drug label were identified, such as anosognosia, attentional drift, and psychogenic compensation disorder.ConclusionAsenapine carries the risk of various adverse reactions alongside its therapeutic effects. In clinical practice, physicians should closely monitor the occurrence of neurological disorders, psychiatric disorders, and gastrointestinal system disorders.
| S-EPMC11318301 | biostudies-literature
Project description:BACKGROUND: Sequencing-by-synthesis technologies significantly improve over the Sanger method in terms of speed and cost per base. However, they still usually fail to compete in terms of read length and quality. Current high-throughput implementations of the pyrosequencing technique yield reads whose length approach those of the capillary electrophoresis method. A less obvious question is whether their quality is affected by platform-specific sequencing errors. RESULTS: We present an empirical study aimed at assessing the quality and characterising sequencing errors for high throughput pyrosequencing data. We have developed a procedure for extracting sequencing error data from genome assemblies and study their characteristics, in particular the length distribution of indel gaps and their relation to the sequence contexts where they occur. We used this procedure to analyse data from three prokaryotic genomes sequenced with the GS FLX technology. We also compared two models previously employed with success for peptide sequence alignment. CONCLUSIONS: We observed an overall very low error rate in the analysed data, with indel errors being much more abundant than substitutions. We also observed a dependence between the length of the gaps and that of the homopolymer context where they occur. As with protein alignments, a power-law model seems to approximate the indel errors more accurately, although the results are not so conclusive as to justify a depart from the commonly used affine gap penalty scheme. In whichever case, however, our procedure can be used to estimate more realistic error model parameters.
| S-EPMC3852801 | biostudies-literature
Project description:Mining high-order drug-drug interaction (DDI) induced adverse drug effects from electronic health record databases is an emerging area, and very few studies have explored the relationships between high-order drug combinations. We investigate a novel pharmacovigilance problem for mining directional DDI effects on myopathy using the FDA Adverse Event Reporting System (FAERS) database. Our paper provides information on the risk of myopathy associated with adding new drugs on the already prescribed medication, and visualizes the identified directional DDI patterns as user-friendly graphical representation. We utilize the Apriori algorithm to extract frequent drug combinations from the FAERS database. We use odds ratio to estimate the risk of myopathy associated with directional DDI. We create a tree-structured graph to visualize the findings for easy interpretation. Our method confirmed myopathy association with previously reported HMG-CoA reductase inhibitors like rosuvastatin, fluvastatin, simvastatin, and atorvastatin. New, previously unidentified but mechanistically plausible associations with myopathy were also observed, such as the DDI between pamidronate and levofloxacin. Additional top findings are gadolinium-based imaging agents, which however are often used in myopathy diagnosis. Other DDIs with no obvious mechanism are also reported, such as that of sulfamethoxazole with trimethoprim and potassium chloride. This study shows the feasibility to estimate high-order directional DDIs in a fast and accurate manner. The results of the analysis could become a useful tool in the specialists' hands through an easy-to-understand graphic visualization.
| S-EPMC6745690 | biostudies-literature
Project description:Background: Unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) are commonly used anticoagulants for the management of arterial and venous thromboses. However, it is crucial to be aware that LMWH can, in rare cases, lead to a dangerous complication known as heparin-induced thrombocytopenia (HIT). The objective of this study was to evaluate the pharmacovigilance and clinical features of HIT associated with LMWH, as well as identify treatment strategies and risk factors to facilitate prompt management. Methods: We extracted adverse event report data from the FDA Adverse Event Reporting System (FAERS) database for pharmacovigilance assessment. Case reports on LMWH-induced thrombocytopenia dated up to 20 March 2023 were collected for retrospective analysis. Results: Significantly elevated reporting rates of HIT were shown in adverse event (AE) data of LMWHs in the FAERS database, while tinzaparin had a higher proportional reporting ratio (PRR) and reporting odds ratio (ROR) than other LMWHs, indicating a greater likelihood of HIT. Case report analysis indicated that a total of 43 patients showed evidence of LMWH-induced thrombocytopenia with a median onset time of 8 days. Almost half of the events were caused by enoxaparin. LMWHs were mainly prescribed for the treatment of embolism and thromboprophylaxis of joint operation. Patients with a history of diabetes or surgery appeared to be more susceptible to HIT. Clinical symptoms were mostly presented as thrombus, skin lesion, and dyspnea. Almost 90% of the patients experienced a platelet reduction of more than 50% and had a Warkentin 4T score of more than 6, indicating a high likelihood of HIT. In all patients, LMWHs that were determined to be the cause were promptly withdrawn. Following the discontinuation of LMWHs, almost all patients were given alternative anticoagulants and eventually achieved recovery. Conclusion: LMWH-induced thrombocytopenia is rare but serious, with increased risk in patients with diabetes or a surgical history. Prompt recognition and management are crucial for the safe use of LMWHs.
| S-EPMC10552922 | biostudies-literature
Project description:BACKGROUND:Adverse drug events (ADEs) often occur as a result of drug-drug interactions (DDIs). The use of data mining for detecting effects of drug combinations on ADE has attracted growing attention and interest, however, most studies focused on analyzing pairwise DDIs. Recent efforts have been made to explore the directional relationships among high-dimensional drug combinations and have shown effectiveness on prediction of ADE risk. However, the existing approaches become inefficient from both computational and illustrative perspectives when considering more than three drugs. METHODS:We proposed an efficient approach to estimate the directional effects of high-order DDIs through frequent itemset mining, and further developed a novel visualization method to organize and present the high-order directional DDI effects involving more than three drugs in an interactive, concise and comprehensive manner. We demonstrated its performance by mining the directional DDIs associated with myopathy using a publicly available FAERS dataset. RESULTS:Directional effects of DDIs involving up to seven drugs were reported. Our analysis confirmed previously reported myopathy associated DDIs including interactions between fusidic acid with simvastatin and atorvastatin. Furthermore, we uncovered a number of novel DDIs leading to increased risk for myopathy, such as the co-administration of zoledronate with different types of drugs including antibiotics (ciprofloxacin, levofloxacin) and analgesics (acetaminophen, fentanyl, gabapentin, oxycodone). Finally, we visualized directional DDI findings via the proposed tool, which allows one to interactively select any drug combination as the baseline and zoom in/out to obtain both detailed and overall picture of interested drugs. CONCLUSIONS:We developed a more efficient data mining strategy to identify high-order directional DDIs, and designed a scalable tool to visualize high-order DDI findings. The proposed method and tool have the potential to contribute to the drug interaction research and ultimately impact patient health care. AVAILABILITY AND IMPLEMENTATION:http://lishenlab.com/d3i/explorer.html.
| S-EPMC7079342 | biostudies-literature
Project description:Lacosamide was the first approved third-generation antiepileptic drug. However, real-world data regarding its adverse cardiac reactions in large samples still need to be completed. We evaluated the cardiac safety profile of lacosamide using the Food and Drug Administration Adverse Event Reporting System (FAERS). We performed disproportionality analysis computing reporting odds ratio (ROR) as a quantitative metric to assess the signal of lacosamide-related cardiac adverse events (AEs) from 2013 Q1 to 2022 Q4. The signal was considered significant when the lower limit of the 95% confidence interval (CI) of the ROR exceeded 1, and ≥ 5 AEs were reported. Serious and nonserious cases were compared by statistical analysis, and signals were further prioritized using a rating scale. A total of 812 cardiac AEs associated with lacosamide were identified, and 92 signals were detected, of which 17 AEs were significantly associated signals. The median time-to-onset (TTO) for moderate priority signals was 10 days, whereas for weak priority signals, it was 54 days. Notably, all cardiac AEs exhibited an early failing pattern, indicating the risk gradually decreasing. Based on the comprehensive analysis of the FAERS database and prioritization of cardiac AE signals, our research enhances the awareness among healthcare professionals regarding cardiac AEs associated with lacosamide.
| S-EPMC11246456 | biostudies-literature
Project description:The published experience with biologics in childbearing age with autoimmune and inflammatory diseases mainly deals with the use of TNFα inhibitors (TNFα-i). Limited data are available for biologics targeting other cytokines or immunocompetent cells, especially for the inflammasome targeted therapy including IL-1 inhibitors and colchicine. We conducted a nested case-control study by using the US Food and Drug Administration Adverse Event Reporting System database aimed at quantifying the association between the use of IL-1 inhibitors/colchicine in pregnant women and the occurrence of maternal/fetal adverse effects. The reporting odds ratio was used as a measure of disproportional reporting. From the total cohort (40,033 pregnant women), we retrieved 7,620 reports related to neonatal AEs, 2,889 to fetal disorders, 8,364 to abortion, 8,787 to congenital disorders, and 7,937 to labor/delivery complications. Inflammasome-targeted drugs did not present any disproportionate reporting for all these clusters of AEs. TNFα-i confirmed their safety during pregnancy with aROR < 1 for all clusters of AEs except for labor complications. Finally, we performed a systematic review of the current literature. Data from the eligible studies (12 observational studies and 6 case reports; yielding a total of 2,075 patients) were reassuring. We found no major safety issues on malformations risk of inflammasome targeted therapies in pregnancy. However, due to limited data, the routine use of these agents should be considered in pregnancy only if risk benefit assessment justifies the potential risk to the fetus.
| S-EPMC7854464 | biostudies-literature