Adverse Event Reporting System Data Research Articles

Safety analysis of Oseltamivir and Baloxavir Marboxil after market approval: a pharmacovigilance study based on the FDA adverse event reporting system

Background and objectivesAmidst limited influenza treatment options, evaluating the safety of Oseltamivir and Baloxavir Marboxil is crucial, particularly given their comparable efficacy. This study investigates post-market safety profiles, exploring adverse events (AEs) and their drug associations to provide essential clinical references.MethodsA meticulous analysis of FDA Adverse Event Reporting System (FAERS) data spanning the first quarter of 2004 to the fourth quarter of 2022 was conducted. Using data mining techniques like reporting odds ratio (ROR), proportional reporting ratio, Bayesian Confidence Propagation Neural Network, and Multiple Gamma Poisson Shrinkage, AEs related to Oseltamivir and Baloxavir Marboxil were examined. Venn analysis compared and selected specific AEs associated with each drug.ResultsIncorporating 15,104 Oseltamivir cases and 1,594 Baloxavir Marboxil cases, Wain analysis unveiled 21 common AEs across neurological, psychiatric, gastrointestinal, dermatological, respiratory, and infectious domains. Oseltamivir exhibited 221 significantly specific AEs, including appendicolith [ROR (95% CI), 459.53 (340.88 ∼ 619.47)], acne infantile [ROR (95% CI, 368.65 (118.89 ∼ 1143.09)], acute macular neuroretinopathy [ROR (95% CI), 294.92 (97.88 ∼ 888.64)], proctitis [ROR (95% CI), 245.74 (101.47 ∼ 595.31)], and Purpura senile [ROR (95% CI), 154.02 (81.96 ∼ 289.43)]. designated adverse events (DMEs) associated with Oseltamivir included fulminant hepatitis [ROR (95% CI), 12.12 (8.30-17.72), n=27], ventricular fibrillation [ROR (95% CI), 7.68 (6.01–9.83), n=64], toxic epidermal necrolysis [ROR (95% CI), 7.21 (5.74–9.05), n=75]. Baloxavir Marboxil exhibited 34 specific AEs, including Melaena [ROR (95% CI), 21.34 (14.15–32.18), n = 23], cystitis haemorrhagic [ROR (95% CI), 20.22 (7.57-54.00), n = 4], ileus paralytic [ROR (95% CI), 18.57 (5.98–57.71), n = 3], and haemorrhagic diathesis [ROR (95% CI), 16.86 (5.43–52.40)), n = 3]. DMEs associated with Baloxavir Marboxil included rhabdomyolysis [ROR (95% CI), 15.50 (10.53 ∼ 22.80), n = 26].ConclusionMonitoring fulminant hepatitis during Oseltamivir treatment, especially in patients with liver-related diseases, is crucial. Oseltamivir’s potential to induce abnormal behavior, especially in adolescents, necessitates special attention. Baloxavir Marboxil, with lower hepatic toxicity, emerges as a potential alternative for patients with liver diseases. During Baloxavir Marboxil treatment, focused attention on the occurrence of rhabdomyolysis is advised, necessitating timely monitoring of relevant indicators for those with clinical manifestations. The comprehensive data aims to provide valuable insights for clinicians and healthcare practitioners, facilitating an understanding of the safety profiles of these influenza treatments in real-world scenarios.

Safety of marketed biosimilar monoclonal antibody cancer treatments in the US: a disproportionality analysis using the food and drug administration adverse event reporting system (FAERS) database

ABSTRACT Background By 31 December 2022, the United States Food and Drug Administration (FDA) has approved 12 biosimilar monoclonal antibody cancer treatments. This study detected disproportionate adverse event (AE) reporting signals and compared safety profile of individual biosimilars to their originator biologics and between each pair of biosimilars. Research design and methods The FDA Adverse Event Reporting System data (6/1/2018–12/31/2022) were used to identify AE reports for rituximab, bevacizumab, trastuzumab, and their marketed biosimilars. Reporting odds ratios and empirical Bayesian geometric mean were computed to detect reporting disproportionality in serious, death, and specific AEs between studied biologics/biosimilars and all other drugs. Results Significant AE reporting signals were identified: 1) death for biological rituximab, pruritus for biosimilar rituximab-pvvr, and infusion-related reactions for biological rituximab and biosimilar rituximab-pvvr (significantly higher ROR for rituximab-pvvr than biological rituximab, p < .0001); 2) death for biological bevacizumab and biosimilar bevacizumab-bvzr (significantly higher ROR for bevacizumab-bvzr than biological bevacizumab, p < .0001), hypertension, platelet count decreased (PCD), and proteinuria for biological bevacizumab and biosimilar bevacizumab-awwb (significantly higher ROR of PCD for bevacizumab-awwb than originator bevacizumab, p = .001); and 3) rash for biosimilar trastuzumab-anns. Conclusions Findings call for large, longitudinal studies to examine causality of certain AEs with rituximab-pvvr and bevacizumab biosimilars.

Unraveling cephalosporin-associated anaphylaxis: A comprehensive analysis using FDA Adverse Event Reporting System data

Unraveling cephalosporin-associated anaphylaxis: A comprehensive analysis using FDA Adverse Event Reporting System data

Drugs associated with serum sickness and serum sickness–like reactions: A review of FDA Adverse Event Reporting System (FAERS) data

Drugs associated with serum sickness and serum sickness–like reactions: A review of FDA Adverse Event Reporting System (FAERS) data

Comparison of thrombotic adverse events in patients treated with factor VIII products and emicizumab using the 2018-2022 US Food and Drug Administration Adverse Event Reporting System data

BackgroundRelatively little is known about thrombotic adverse events (AEs) of emicizumab in postmarketing real-world settings, particularly in comparison with factor VIII (FVIII) products. A recent European study reported a greater thrombotic risk of emicizumab compared with FVIII products. ObjectivesThis drug safety study aims to investigate whether thrombotic AEs are more frequently reported for emicizumab than for FVIII products and if so, whether it is independent of bypassing agents as coreporting drugs using the US Food and Drug Administration Adverse Event Reporting System data. MethodsDisproportionality analyses for thrombotic AEs of emicizumab vs FVIII products were conducted. Three signal detection indicators were used: proportional reporting ratio (PRR), reporting odds ratio (ROR), and informational component (IC). ResultsDuring 2018-2022, the proportions of thrombotic AEs among all AEs were 4.07% (97 out of 2383) and 1.44% (134 out of 9324) for emicizumab and FVIII products, respectively: PRR = 2.83 (2.19-3.66), ROR = 2.91 (2.23-3.79), and IC = 1.04 (0.70-1.28). Bypassing agents as coreporting drugs were identified in 36% and 15% of the total thrombotic AE reports associated with emicizumab and FVIII products, respectively. Even after thrombotic AE reports with bypassing agents were excluded, the reporting proportion of thrombotic AEs was still greater for emicizumab than for FVIII products: PRR = 2.19 (1.60-2.99). ConclusionThrombotic AEs in the US Food and Drug Administration Adverse Event Reporting System data were about 3 times more frequently reported for emicizumab than for FVIII products. More research and efforts in the future are warranted for monitoring, elucidating, and preventing the potential risk of thrombotic AEs in hemophilia therapy, including emicizumab.

An Updated Comprehensive Pharmacovigilance Study of Drug-Induced Thrombocytopenia Based on FDA Adverse Event Reporting System Data.

Drug-induced thrombocytopenia (DIT) deserves both clinical and research attention for the serious clinical consequences and high prevalence of the condition. The current study aimed to perform a comprehensive pharmacovigilance analysis of DIT reported in the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database, with a particular focus on drugs associated with thrombocytopenia events. A disproportionality analysis of DIT was conducted using reports submitted to FARES from January 2004 to December 2022. Both the information component (IC) and reporting odds ratio (ROR) algorithms were applied to identify an association between target drugs and DIT events. A total of 15,940,383 cases were gathered in FAERS, 168,657 of which were related to DIT events. The top 50 drugs ranked by number of cases and ranked by signal strength were documented. The top 5 drugs ranked by number of cases were lenalidomide (10,601 cases), niraparib (3726 cases), ruxolitinib (3624 cases), eltrombopag (3483 cases), and heparin (3478 cases). The top 5 drugs ranked by signal strength were danaparoid (ROR37.61, 95%CI 30.46-46.45), eptifibatide (ROR34.75, 95%CI 30.65-39.4), inotersen (ROR34.00, 95%CI 29.47-39.23), niraparib (ROR30.53, 95%CI 29.42-31.69), and heparin (ROR28.84, 95%CI 27.76-29.97). The top 3 involved drug groups were protein kinase inhibitors, antimetabolites, and monoclonal antibodies and antibody-drug conjugates. The current comprehensive pharmacovigilance study identified more drugs associated with thrombocytopenia. Although the mechanisms of DIT have been elucidated for some drugs, others still require further investigation.

Unpacking adverse events and associations post COVID-19 vaccination: a deep dive into vaccine adverse event reporting system data

ABSTRACT Introduction The rapid development of COVID-19 vaccines has provided crucial tools for pandemic control, but the occurrence of vaccine-related adverse events (AEs) underscores the need for comprehensive monitoring. Methods This study analyzed the Vaccine Adverse Event Reporting System (VAERS) data from 2020–2022 using statistical methods such as zero-truncated Poisson regression and logistic regression to assess associations with age, gender groups, and vaccine manufacturers. Results Logistic regression identified 26 System Organ Classes (SOCs) significantly associated with age and gender. Females displayed especially higher odds in SOC 19 (Pregnancy, puerperium and perinatal conditions), while males had higher odds in SOC 25 (Surgical and medical procedures). Older adults (>65) were more prone to symptoms like Cardiac disorders, whereas those aged 18–65 showed susceptibility to AEs like Skin and subcutaneous tissue disorders. Moderna and Pfizer vaccines induced fewer SOC symptoms compared to Janssen and Novavax. The zero-truncated Poisson regression model estimated an average of 4.243 symptoms per individual. Conclusion These findings offer vital insights into vaccine safety, guiding evidence-based vaccination strategies and monitoring programs for precise and effective outcomes.

Metformin-Cimetidine Drug Interaction and Risk of Lactic Acidosis in Renal Failure: A Pharmacovigilance-Pharmacokinetic Appraisal.

This study aimed to evaluate lactic acidosis (LA) risk when using metformin combined with histamine H2 receptor inhibitors (H2RI) in patients with renal failure (RF). This study analyzed FDA Adverse Event Reporting System data (2012Q4 to 2022Q4) to characterize reports of LA associated with metformin alone or combined with H2RI. Using a disproportionality approach, LA risk signal in the overall population and in patients with RF was assessed. A physiologically based pharmacokinetic (PBPK) model was developed to predict metformin and cimetidine pharmacokinetic changes following conventional doses of the combinations in patients with various degrees of RF. To explore its correlation with LA risk, a peak plasma metformin concentration of 3 mg/L was considered the threshold. Following the 2016 U.S. Food and Drug Administration metformin approval for mild-to-moderate RF, the percentage of patients with RF reporting LA associated with metformin combined with H2RI increased. Disproportionality analysis showed reported LA risk signal associated with metformin and cimetidine in the overall population within the study timeframe only. Furthermore, with PBPK simulations, for metformin (1,000 mg b.i.d.) with cimetidine (300 mg q.i.d. or 400 mg b.i.d.) in stage 1 of chronic kidney disease, metformin (1,000 mg b.i.d.) with cimetidine (300 mg q.i.d. or 400 mg b.i.d. or 800 mg q.d.) in stage 2, and most combinations in stage 3, the peak plasma metformin concentrations exceeded the 3 mg/L threshold. Metformin combined with cimetidine at conventional doses may cause LA in patients with mild-to-moderate RF.

Association of temozolomide with progressive multifocal leukoencephalopathy: a disproportionality analysis integrated with network pharmacology

ABSTRACT Background Temozolomide (TMZ) is an alkylating agent approved for the management of glioblastoma. The TMZ is not known for progressive multifocal leukoencephalopathy (PML). The main objective of the current study is to find out the association of TMZ with PML using disproportionality analysis of FDA Adverse Event Reporting System (FAERS) data integrated with network pharmacological approaches. Research design and methods OpenVigil tool was used to query the FAERS database. The disproportionality measures were calculated. The network has been constructed using Cytoscape. Finally, the possible binding interactions were studied using Glide, Schrödinger Inc. Results A total number of 3502 cases of PML were reported in the FAERS database. Out of these, 10 cases were found with TMZ. The subgroup analysis results have shown a greater number of cases in females. The network has indicated the involvement of human mitogen-activated protein kinase, 3-phosphoinositide-dependent protein kinase 1 protein, human mTOR complex protein, phosphatidylinositol 4,5-bisphosphate 3-kinase protein, and glycogen synthase kinase-3 beta protein. The docking results have indicated good interactions of TMZ with active site of glycogen synthase kinase-3 beta and mitogen-activated protein kinase 1 as compared to other identified targets. Conclusion The PML is identified as novel signal with temozolomide.

A real-world analysis of tyrosine receptor kinase inhibitor-related toxicities in cancer treatment.

Background: This study analyzed real-world data from 2004 to 2023 to evaluate the toxicity profile of tyrosine receptor kinase (TRK) inhibitor therapy. Method: A retrospective analysis of USFDA Adverse Event Reporting System data was conducted to identify adverse events in patients receiving TRK inhibitor therapy. Result: Entrectinib demonstrated toxicities primarily in the cardiovascular and nervous systems, followed by the renal and urinary system. Common adverse effects included dizziness, renal impairment, constipation, heart failure and taste disorders. Larotrectinib induced adverse events mainly in the hepatobiliary and nervous systems, with peripheral neuropathy, myalgia, renal impairment and increased alanine aminotransferase commonly reported. Conclusion: Careful monitoring and supportive care strategies are essential for managing adverse events associated with TRK inhibitor therapy.

A Case of Generalized Edema in a Patient after COVID-19 Vaccination Improved by a Combined Korean-Western Medicine Approach

Background: According to Vaccine Adverse Events Reporting System data, generalized edema followed by the COVID-19 vaccine is uncommon, with only 333 reported cases, and of those, 224 (69%) are associated with the Pfizer-BioNTech vaccine.Case report: A 76-year-old male patient with heart failure with preserved ejection fraction presented with spontaneous generalized edema and otherwise normal cardiac exams following administration of BNT162b2 (Pfizer-BioNTech) COVID-19 vaccination that had lasted for approximately 60 days and was treated successfully using Korean medicine treatment. After the administration of Korean medicine treatment, the patient’s symptoms in the bilateral limbs were dramatically controlled, without recurrence, for 2 months. As a result, generalized edema, which had been present for approximately 50 days, dramatically improved.Conclusion: This clinical case study suggests that a Korean medicine approach with &lt;i&gt;Mokbangki-tang&lt;/i&gt; and &lt;i&gt;Oryeong-san&lt;/i&gt; might be effective for the pleural effusion resolution of generalized edema after COVID-19 vaccination.

Comprehensive Study of Drug-Induced Pruritus Based on Adverse Drug Reaction Report Database.

Drug-induced pruritus triggers a desire to scratch, thereby diminishing one's quality of life. Certain instances of this phenomenon follow complex mechanisms of action that diverge from histamine-mediated pathways, known contributors to pruritus. However, investigations into the relationship between drugs and pruritus are limited. In this study, data mining techniques were employed to comprehensively analyze the characteristics of drugs linked to pruritus, using the FDA's Adverse Event Reporting System (FAERS) data. Reports linked to pruritus demonstrated noteworthy differences in gender, age, and weight when compared with non-pruritus cases. Among the leading candidates for drugs prompting pruritus were ophthalmic drugs, systemic antibacterials, contrast media, dermatological antifungals, and dermatological preparations. A principal component analysis showed that the second principal component served as an indicator for distinguishing between onsets at mucous membranes or the skin's surface. Additionally, the third principal component functioned as an indicator for categorizing administration methods as either invasive or noninvasive. Furthermore, a hierarchical cluster analysis conducted on these obtained principal components revealed the potential for classifying drugs based on the site of pruritus onset and the method of drug administration. These findings contribute to the development of targeted prevention and treatment strategies for avoiding pruritus in clinical practice.

Analysis of the adverse events following the mRNA-1273 COVID-19 vaccine

ABSTRACTObjectiveThis study aims to characterize the adverse events (AEs) following the administration of the mRNA-1273 COVID-19 vaccine from the Vaccine Adverse Event Reporting System (VAERS) data.MethodsIn this case/non-case analysis, reports between 1 January 2021, and 27 October 2022, were extracted from VAERS. AEs were defined as preferred terms (PTs) by Medical Dictionary for Regulatory Activities (MedDRA) terminology. Disproportionality analyses were conducted to calculate the reporting odds and proportional reporting ratios. The Bayesian approach was used to calculate information component (IC) values and Empirical Bayesian Geometric Mean scores for all the AEs detected.Results186 MedDRA PTs compromising 702,495 AEs associated with the mRNA-1273 vaccine were identified. Three statistically significant signals were identified for general and systemic AEs, administration site conditions, and product issues. Cardiac disorders were rarely reported, the most common being; 489 reports for ‘myocarditis’ (19.44%), 475 for ‘acute myocardial infarction’ (18.88%), 457 for ‘myocardial infarction’ (18.16%), 290 for ‘bradycardia’ (11.53%) and 281 for ‘pericarditis’ (11.17%).ConclusionsThe most frequently identified AEs following mRNA-1273 vaccination agree with those listed within the Summary of Product Characteristics. In addition, disproportionality analysis did not find any statistically significant signals for myocarditis or pericarditis.

Janus kinase inhibitor—Tofacitinib associated with pemphigus: an analysis of the FDA adverse event reporting system data

ABSTRACT Objectives To establish the association between the therapy of Janus kinase inhibitors and the adverse event of pemphigus in patients with rheumatologic and inflammatory disorders. Methods A disproportionality analysis using multi-item gamma Poisson shrinker was conducted to identify signals between medication and adverse events within the FDA Adverse Event Reporting System. Results The spontaneous reporting system contained 3,032 pemphigus reports associated with two Janus kinase inhibitors, namely Tofacitinib and Upadacitinib. The year/reporter/geographic area/country/age/sex/indication with the highest number of cases were the year of 2021, physician, North America, Canada, age between 40–49, female and rheumatoid arthritis, respectively. A significant signal was detected in the Tofacitinib group. Conclusion Pemphigus, a rare and potentially fatal adverse event, was found to occur more frequently in patients receiving Tofacitinib. High-risk individuals were identified as female, age between 40–49, or with rheumatoid arthritis. Medication, adverse events, and underlying disease conditions were identified as potential contributing factors. Rheumatology and dermatology specialists should exercise increased vigilance in clinical practice.

A pharmacovigilance study of the association between antipsychotic drugs and venous thromboembolism based on Food and Drug Administration Adverse Event Reporting System data

ABSTRACT Background This study aimed to measure and present a comprehensive overview of the association of antipsychotic drugs and venous thromboembolism (VTE) in the Food and Drug Administration Adverse Event Reporting System (FAERS). Method: All VTE cases treated with antipsychotic drugs as primary suspected medicines were extracted from the FAERS database from 2004 to 2021. Disproportionality analyses were conducted by estimating the reporting odds ratio (ROR) and the information component (IC). Results In the FAERS system, 4,455 VTE cases associated with antipsychotics were identified. The VTE signal was detected with olanzapine, haloperidol, paliperidone, and quetiapine. The RORs and 95% confidence intervals (95% CI) of olanzapine, haloperidol, paliperidone, and quetiapine were (ROR = 2.53 95% Cl 2.38–2.69 IC = 1.31 95% Cl 1.11–1.52), (ROR = 2.17 95% Cl 1.91–2.46 IC = 1.1 95% Cl 0.66–1.52), (ROR = 1.6 95% Cl 1.4–1.83 IC = 0.67 95% Cl 0.22–1.11), and (ROR = 1.37 95% Cl 1.28–1.47 IC = 0.45 95% Cl 0.23–0.67). Pulmonary embolism occurred in more than 50% of VTE events (2760 cases, 52.84%). Conclusion The data mining of FAERS suggested an association between VTE and antipsychotic drugs, which reminds medical workers to pay attention to the serious adverse drug effects of antipsychotic drugs leading to venous thromboembolism.

Interstitial lung disease risk of anaplastic lymphoma kinase tyrosine kinase inhibitor treatment of non-small cell lung cancer: a real-world pharmacovigilance study

ABSTRACT Background Interstitial lung disease (ILD) is a rare but life-threatening and fatal treatment-related pneumonitis. This study investigated the association between anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) and ILD. Research design and Methods Cases of ILD that developed after treatment with an ALK-TKI in the Food and Drug Administration’ s Adverse Event Reporting System (FAERS) data were assessed. We also described the clinical features of these cases and evaluated onset time, hospitalization, life-threatening condition, and fatality rate of ILD developed after treatment with an ALK-TKI. Results All five ALK-TKI regimens were significantly associated with ILD. The median onset time to ILD was significantly different for brigatinib, crizotinib, alectinib, lorlatinib, and ceritinib: 4.5, 25, 35.5, 54.5, and 84 days, respectively. ALK-TKI-associated ILD resulted in hospitalization in 55.77% of patients and death or life-threatening outcomes in 43.03%. The highest and lowest proportions of ILD-related fatalities were observed after crizotinib and alectinib treatment, respectively. Conclusions ALK-TKIs were associated with ILD; therefore, the risk of developing ILD after treatment with an ALK-TKI should be carefully considered in clinical settings.

Exploring the impact of design criteria for reference sets on performance evaluation of signal detection algorithms: The case of drug-drug interactions.

To evaluate the impact of multiple design criteria for reference sets that are used to quantitatively assess the performance of pharmacovigilance signal detection algorithms (SDAs) for drug-drug interactions (DDIs). Starting from a large and diversified reference set for two-way DDIs, we generated custom-made reference sets of various sizes considering multiple design criteria (e.g., adverse event background prevalence). We assessed differences observed in the performance metrics of three SDAs when applied to FDA Adverse Event Reporting System (FAERS) data. For some design criteria, the impact on the performance metrics was neglectable for the different SDAs (e.g., theoretical evidence associated with positive controls), while others (e.g., restriction to designated medical events, event background prevalence) seemed to have opposing and effects of different sizes on the Area Under the Curve (AUC) and positive predictive value (PPV) estimates. The relative composition of reference sets can significantly impact the evaluation metrics, potentially altering the conclusions regarding which methodologies are perceived to perform best. We therefore need to carefully consider the selection of controls to avoid misinterpretation of signals triggered by confounding factors rather than true associations as well as adding biases to our evaluation by "favoring" some algorithms while penalizing others.

Comparison of Adverse Events Occurred During Administration of Dipeptidyl Peptidase-4 Inhibitor in Patients with Diabetes Using FDA Adverse Event Reporting System.

Various dipeptidyl peptidase-4 (DPP-4) inhibitors have been approved for the treatment of diabetes. The frequencies of known serious side effects might differ among DPP-4 inhibitors, therefore a large sample size is needed to study them in prospective clinical trials. We examined the adverse events that occurred during the administration of a DPP-4 inhibitor in patients with diabetes using FDA Adverse Event Reporting System (FAERS) data. We used FAERS data reported between January 2013 and March 2022 in patients with diabetes who received a DPP-4 inhibitor. Statistical analyses were conducted to calculate reporting odds ratio (ROR) and adjusted ROR (aROR) controlling for differences in patient background. The 9 target DPP-4 inhibitors were sitagliptin (N = 26,843), vildagliptin (N = 4767), alogliptin (N = 2085), linagliptin (N = 7969), saxagliptin (N = 3334), teneligliptin (N = 461), anagliptin (N = 102), trelagliptin (N = 17), and omarigliptin (N = 12). Compared with sitagliptin, aROR of acute kidney injury was significantly < 1.000 for alogliptin (0.247 [95% confidence interval (CI) 0.150-0.408], p < 0.001) but aROR of pemphigoid was significantly > 1.000 for alogliptin (3.082 [95% CI 2.156-4.406], p < 0.001). Similar statistical analyses were conducted for other adverse events and the types of adverse events with aROR of significantly < 1.000 or > 1.000 differed depending on the type of DPP-4 inhibitor. Although it is impossible to select a DPP-4 inhibitor with aROR of < 1.000 of all occurrences of adverse events, these results may be used for drug selection when the patient has adverse events that need to be avoided. We provided the sample code of software R that can reproduce the results.

Platinum drugs-related safety profile: The latest five-year analysis from FDA adverse event reporting system data.

With the widespread application of platinum drugs in antitumor therapy, the incidence of platinum drug adverse events (ADEs) is always severe. This study aimed to explore the adverse event signals of Cisplatin, Carboplatin and Oxaliplatin, three widely used platinum-containing drugs, and to provide a reference for rational individualized clinical drug use. The adverse event report data of the three platinum drugs from the first quarter of 2017 to the fourth quarter of 2021 were extracted from the FAERS database, and the data mining and risk factors for the relevant reports were carried out using the reporting odds ratio (ROR) method the proportional reporting ratio (PRR)and the comprehensive criteria (MHRA) method. A total of 1853 effective adverse event signals were obtained for the three platinum agents, including 558 effective signals for Cisplatin, 896 effective signals for Carboplatin, and 399 effective signals for Oxaliplatin. The signals involve 23 effective different system organs (SOCs). The adverse events of Cisplatin are mainly fixed on blood and lymphatic system diseases, gastrointestinal diseases, systemic diseases and various reactions at the administration site. The adverse events of Carboplatin are mainly focused on blood and lymphatic system diseases, respiratory system, thoracic and mediastinal diseases, while the adverse events of Oxaliplatin are mainly concentrated in respiratory system, thoracic and mediastinal diseases, various nervous system diseases, and gastrointestinal system diseases. It was found that the main systems involved in common adverse events of platinum drugs are different, and the correlation strength of platinum drugs with the certain adverse events of each system is different.

Evaluation of four machine learning models for signal detection.

Logistic regression-based signal detection algorithms have benefits over disproportionality analysis due to their ability to handle potential confounders and masking factors. Feature exploration and developing alternative machine learning algorithms can further strengthen signal detection. Our objective was to compare the signal detection performance of logistic regression, gradient-boosted trees, random forest and support vector machine models utilizing Food and Drug Administration adverse event reporting system data. Cross-sectional study. The quarterly data extract files from 1 October 2017 through 31 December 2020 were downloaded. Due to an imbalanced outcome, two training sets were used: one stratified on the outcome variable and another using Synthetic Minority Oversampling Technique (SMOTE). A crude model and a model with tuned hyperparameters were developed for each algorithm. Model performance was compared against a reference set using accuracy, precision, F1 score, recall, the receiver operating characteristic area under the curve (ROCAUC), and the precision-recall curve area under the curve (PRCAUC). Models trained on the balanced training set had higher accuracy, F1 score and recall compared to models trained on the SMOTE training set. When using the balanced training set, logistic regression, gradient-boosted trees, random forest and support vector machine models obtained similar performance evaluation metrics. The gradient-boosted trees hyperparameter tuned model had the highest ROCAUC (0.646) and the random forest crude model had the highest PRCAUC (0.839) when using the balanced training set. All models trained on the balanced training set performed similarly. Logistic regression models had higher accuracy, precision and recall. Logistic regression, random forest and gradient-boosted trees hyperparameter tuned models had a PRCAUC ⩾ 0.8. All models had an ROCAUC ⩾ 0.5. Including both disproportionality analysis results and additional case report information in models resulted in higher performance evaluation metrics than disproportionality analysis alone.