A Standardized Dataset of a Spontaneous Adverse Event Reporting System

Khaleel, Mohammad A.; Khan, Amer Hayat; Ghadzi, Siti Maisharah Sheikh; Adnan, Azreen Syazril; Abdallah, Qasem

doi:10.3390/healthcare10030420

Cited by 32 publications

(25 citation statements)

References 26 publications

(32 reference statements)

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“…The co-reported toxicities’ landscape among sepsis-related toxicities shows that sepsis, septic shock, and multiple organ dysfunction syndrome not only overlap with each other but also with other serious toxicities such as veno-occlusive liver disease ( Figure 2 ). To evaluate the onset of ADC-induced sepsis, we conducted time-to-onset analysis using a curated FAERS dataset ( Khaleel et al, 2022 ). The β-coefficient and its 95% CI for sepsis, septic shock, and bacteremia were less than one, suggesting that the onset time of ADC-induced sepsis is the early failure type, and approximately 60% of sepsis, septic shock, and bacteremia due to ADC therapies developed within 26.6–32.3 days.…”

Section: Resultsmentioning

confidence: 99%

Do antibody–drug conjugates increase the risk of sepsis in cancer patients? A pharmacovigilance study

et al. 2022

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Introduction: Antibody–drug conjugates (ADCs) produce unparalleled efficacy in refractory neoplasms but can also lead to serious toxicities. Although ADC-related sepsis has been reported, the clinical features are not well characterized in real-world studies.Objective: The aim of this study was to identify the association between ADCs and sepsis using FAERS data and uncover the clinical characteristics of ADC-related sepsis.Methods: We performed disproportionality analysis using FAERS data and compared rates of sepsis in cancer patients receiving ADCs vs. other regimens. Associations between ADCs and sepsis were assessed using reporting odds ratios (RORs) and information component (IC). For each treatment group, we detected drug interaction signals, and conducted subgroup analyses (age, gender, and regimens) and sensitivity analyses.Results: A total of 24,618 cases were reported with ADCs between Q1, 2004 and Q3, 2021. Sepsis, septic shock, multiple organ dysfunction syndrome, and other sepsis-related toxicities were significantly associated with ADCs than other drugs in this database. Sepsis and multiple organ dysfunction syndrome have the highest safety concerns with ADCs compared with other anticancer monotherapies. Gemtuzumab ozogamicin and inotuzumab ozogamicin showed increased safety risks than other ADCs. For the top nine ADC-related sepsis, males showed higher sepsis safety concern than females (p <0.001); however, age did not exert influence on the risk of sepsis. We identified that 973 of 2,441 (39.9%) cases had acute myeloid leukemia (AML), and 766 of 2613 (29.3%) cases on ADCs died during therapy. Time-to-onset analysis indicated ADC-related sepsis is prone to occur within a month after administration. Co-administration of ADCs with colony-stimulating factors, proton pump inhibitors, H2-receptor antagonists, or CYP3A4/5 inhibitors showed to synergistically increase the risk of sepsis-related toxicities.Conclusion: Antibody–drug conjugates may increase the risk of sepsis in cancer patients, leading to high mortality. Further studies are warranted to characterize the underlying mechanisms and design preventive measures for ADC-related sepsis.

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Section: Resultsmentioning

confidence: 99%

Do antibody–drug conjugates increase the risk of sepsis in cancer patients? A pharmacovigilance study

et al. 2022

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“…Thus, we calculated the information component (IC) along with the lower limit of 95% confidence intervals (IC 025 ) using the Bayesian confidence propagation network (BCPNN) algorithm. This protects from over-sensitivity to extremely low expected cases and low observed cases ( 20 , 22 ). An IC 025 of >0 is defined as a signal ( 20 ).…”

Section: Methodsmentioning

confidence: 99%

Disproportionality analysis of quinolone safety in children using data from the FDA adverse event reporting system (FAERS)

Kong

Mao²,

Zhang³

et al. 2023

Front. Pediatr.

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BackgroundQuinolones are widely prescribed for the treatment or prevention of infectious diseases in children. To gain further insight into quinolone-associated adverse event (AE) in children and better protect pediatric patients, continued surveillance of safety data is essential. The purpose of this study was to characterize the safety profiles of quinolone-associated AEs in children by mining the FDA adverse event reporting system (FAERS).MethodsFAERS reports from quarter 1 of 2004 to quarter 1 of 2022 were included in the study. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify adverse events. Reporting odds ratios (ROR) corresponding 95% confidence intervals (CIs) and information component (IC) along with 95% CIs were calculated to detect drug–AE pairs with higher-than-expected reporting rates within the FAERS from System Organ Classes (SOCs) to Preferred Terms (PTs). Reports were considered as signals if the 95% conﬁdence interval did not contain the null value.ResultsAfter inclusion criteria were applied, a total of 4,704 reports associated with quinolones were considered. Most FAERS reports associated with ciprofloxacin (N = 2,706) followed by levofloxacin (N = 1,191), moxifloxacin (N = 375), oflaxacin (N = 245) and ozenoxacin (N = 187). The most common age group was 12–18 years. The median weight was 39.0 kilogram. The adverse effects of quinolones emerging for SOCs primarily included Infections and infestations, gastrointestinal symptoms, blood and lymphatic system disorders, cardiac disorders, nervous system disorders, musculoskeletal and connective tissue disorders and psychiatric disorders. The most frequently AE signals at the PT level were pyrexia (N = 236), febrile neutropenia (N = 120), off label use (N = 48), drug resistance (N = 18) and cardiac arrest (N = 22) following the use of ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin, and ozenoxacin, respectively. Serious oznoxacin-associated AE signals were found and have not been documented in the package insert. They included cardiac arrest (N = 22; ROR = 19.83; IC = 3.68), overdose (N = 21; ROR = 4.98; IC = 2.07), seizure (N = 16; ROR = 6.01; IC = 2.29), small for dates baby (N = 9; ROR = 14.7; IC = 3.05), completed suicide (N = 15, ROR = 18.87; IC = 3.51), asthma (N = 9; ROR = 6.69; IC = 2.24;) and hypotension (N = 9; ROR = 3.83; IC = 1.68).ConclusionThis study provided additional evidence with respect to quinolones-related AEs for children. Generally, the findings of this study are compatible with AEs recorded in package inserts. The unexpected signals of ozenoxacin justify active vigilance by clinicians and timely monitoring by pharmacovigilance experts.

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“…There are two fields in the DRUG files that relate to drug names, including the "drugname" and the "prod_ai." Given that FAERS is a spontaneous reporting system (SRS), drug names may be documented as generic names, chemical structure names, trade names, synonyms, code names, abbreviations, and even incorrect names (13). Therefore, before data mining, all drug name records were standardized in the DEMO files as generic names.…”

Section: Discrimination Of Objective Drugs and Aementioning

confidence: 99%

Gastrointestinal perforation associated with novel antineoplastic agents: A real-world study based on the FDA Adverse Event Reporting System

Yu¹,

Zhu²,

Chen³

et al. 2023

J. pharm. pharm. sci.

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Purpose: Gastrointestinal perforation (GIP) is a fatal adverse event (AE). The AE of GIP induced by novel antineoplastic agents has attracted attention recently. We aimed to explore the AE signals of GIP related to novel antineoplastic agents comprehensively based on the FDA Adverse Event Reporting System (FAERS).Methods: The FAERS database containing 71 quarters of records was used for analysis. Reporting odds ratio (ROR), information component (IC), and empirical Bayesian geometric mean (EBGM) were utilized to evaluate the signals of GIP associated with novel antineoplastic drugs. Standardization of drug names was by employing MedEx-UIMA software and Python. Data analysis and visualization were performed using MySQL Workbench and R software.Results: After cleaning and handling the data, 5226 GIP cases were identified that were associated with new antineoplastic medications, where these agents were the main suspected contributors. A total of 37 novel antineoplastic drugs were detected with signals of GIP for ROR and IC. Only 22 drugs showed statistically significant signals for EBGM. We found the GIP signals of 22 novel antineoplastic drugs overlapped for the 3 indicators, including anti-vascular endothelial growth factor/vascular endothelial growth factor receptor, anti-endothelial growth factor receptor, immune checkpoint inhibitors, and so on.Conclusion: The potential risk of GIP associated with several novel antineoplastic agents was identified through data mining, which provided valuable information on the safety risks associated with GIP among these drugs. The potential threat of GIP should be recognized and managed properly when using these novel antineoplastic agents.

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A Standardized Dataset of a Spontaneous Adverse Event Reporting System

Cited by 32 publications

References 26 publications

Do antibody–drug conjugates increase the risk of sepsis in cancer patients? A pharmacovigilance study

Do antibody–drug conjugates increase the risk of sepsis in cancer patients? A pharmacovigilance study

Disproportionality analysis of quinolone safety in children using data from the FDA adverse event reporting system (FAERS)

Gastrointestinal perforation associated with novel antineoplastic agents: A real-world study based on the FDA Adverse Event Reporting System

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