Text Mining of Adverse Events in Clinical Trials: Deep Learning Approach

Background Pharmacovigilance and safety reporting, which involve processes for monitoring the use of medicines in clinical trials, play a critical role in the identification of previously unrecognized adverse events or changes in the patterns of adverse events. Objective This study aims to demonstrate the feasibility of automating the coding of adverse events described in the narrative section of the serious adverse event report forms to enable statistical analysis of the aforementioned patterns. Methods We used the Unified Medical Language System (UMLS) as the coding scheme, which integrates 217 source vocabularies, thus enabling coding against other relevant terminologies such as the International Classification of Diseases–10th Revision, Medical Dictionary for Regulatory Activities, and Systematized Nomenclature of Medicine). We used MetaMap, a highly configurable dictionary lookup software, to identify the mentions of the UMLS concepts. We trained a binary classifier using Bidirectional Encoder Representations from Transformers (BERT), a transformer-based language model that captures contextual relationships, to differentiate between mentions of the UMLS concepts that represented adverse events and those that did not. Results The model achieved a high F1 score of 0.8080, despite the class imbalance. This is 10.15 percent points lower than human-like performance but also 17.45 percent points higher than that of the baseline approach. Conclusions These results confirmed that automated coding of adverse events described in the narrative section of serious adverse event reports is feasible. Once coded, adverse events can be statistically analyzed so that any correlations with the trialed medicines can be estimated in a timely fashion.

Hepatotoxicity-Related Adverse Effects of Proton Pump Inhibitors: A Cross-Sectional Study of Signal Mining and Analysis of the FDA Adverse Event Report System Database

Background and Objectives: Mounting evidence demonstrates that proton pump inhibitors (PPIs) are associated with a number of adverse effects. However, the literatures about hepatotoxicity-related adverse effects (HRAEs) of PPIs are mostly case reports and a few clinical studies.Methods: We evaluated the association between PPIs and HAREs using the reporting odd ratio (ROR) for mining the adverse event report signals in the FDA Adverse Event Reporting System (FAERS) database.Results: There were 23,825 reports of PPIs as primary suspect drug or second suspect drug, of which 3,253 reports were HRAEs. The top five HRAE signals caused by PPIs were hepatitis cholestatic, cholestasis, fulminant hepatitis, subacute hepatic failure, and acute hepatitis. We also summarized the signals of the HRAEs caused by each PPI. The simultaneous signals were cholestasis and hepatitis cholestatic. For the cholestasis signal, esomeprazole showed an ROR of 21.556 (95% CI 17.592–26.413); pantoprazole showed the highest ROR of 22.611 (95% CI 17.794–28.733) in the hepatic cholestatic signal; lansoprazole was the only PPI with expression in the coma hepatic signal, with an ROR of 10.424 (95% CI 3.340–32.532). By analyzing the reports of pantoprazole-induced hepatic encephalopathy, we found that patients aged over 65 years and males reported the highest rate. And from the combination of drugs and indications of drugs, no significant results were obtained.Conclusions: The RORs of signals of “cholestasis” were generally higher than those of “hepatocellular injury.” And the signals about “cholestasis” in HRAE caused by PPIs are more reported.

Safety of SGLT2 Inhibitors: A Pharmacovigilance Study From 2015 to 2020 Based on FDA Adverse Event Report System Database

Aim: With the widespread use of SGLT2i, various adverse events (AEs) have been reported. This study aimed to describe the distribution of SGLT2i-related AEs in different systems, quantify the association of important medical events (IMEs) and SGLT2i regimens, and build a signal profile of SGLT2i- induced IMEs. Methods: Data from 2015 Q1 to 2020 Q4 in the FDA Adverse Event Reporting System database (FAERS) were selected to conduct disproportionality analysis. Two signal indicators, the reported odds ratio (ROR) and information component (IC), were used to evaluate the correlation between SGLT2i and IMEs. The lower end of the 95% confidence interval of IC (IC025) exceeding zero was deemed a signal. For ROR, it was defined a signal if ROR025 over one, with at least 3 cases. Results: A total of 45,771,436 records were involved, including 111,564 records related to SGLT2i, with 38,366 records of SGLT2i-induced IMEs. Overall, SGLT2i was significantly associated with IMEs (IC=0.36, 95% CI: 0.35-0.38; ROR=1.44, 95% CI: 1.42-1.46). Most SGLT2i-related adverse events occurred in monotherapy (92.93%). Diabetic ketoacidosis was the most IMEs. Specifically, acute osteomyelitis has the strongest signal of all SGLT2i (IC025=7.83), and it was unique to canagliflozin. Diabetic ketoacidosis, acute kidney injury, ketoacidosis, Fournier’s gangrene, and euglycemic diabetic ketoacidosis were common to the four FDA-approved SGLT2i. Conclusion: Our study demonstrated that different SGLT2i regimens lead to different important adverse events, but there are overlapping events. Early identification and management of SGLT2i-associated IMEs are essential for clinical practice.

Ações implementadas no preparo e administração de heparina endovenosa: relato de evento adverso/Actions implemented in the preparation and endovenous administration of heparin: adverse event report

Objetivo: relatar evento adverso no preparo e administração de heparina endovenosa e ações implementadas pela equipe de saúde. Métodos: trata-se de relato de experiência sobre as ações implementadas após análise de evento adverso no preparo e administração de heparina em paciente internado em um Hospital Universitário do Sul do Brasil. Os dados foram coletados nos registros do prontuário do paciente, atas de reuniões das equipes envolvidase do plano de ação das medidas instituídas após evento ocorrido em novembro de 2017. A análise dos resultados foi realizada de forma descritiva e o projeto aprovado por Comitê de Ética em Pesquisa. Resultados: as ações realizadas incluíram a revisão de rotinas e protocolos relacionados ao cálculo de dose, preparo e administração daheparina endovenosa. Houve ainclusão como medicamento de alta vigilância e realização da dupla checagem. Também foram divulgadas orientações e alertas em nível institucional para todos os membros da equipe de enfermagem. Conclusão: a experiência contribuiu para evidenciar a necessidade de monitorar incidentes e seus impactos, encontrar estratégias para reduzi-los por meio de revisões nos processos e implementação de ações naprática assistencial visando maior segurançano preparo e administração de heparina endovenosa.