Exploring pharmacovigilance practices and knowledge among healthcare professionals: A cross-sectional multicenter study.

Introduction: Healthcare professionals' awareness of adverse drug reaction reporting and pharmacovigilance practices differ by country. The study assesses healthcare professionals' knowledge, practice, and potential barriers to pharmacovigilance-related practices and reporting adverse drug reaction. Methods: A cross-sectional investigation was conducted in government and private healthcare settings. The study included licensed physicians, pharmacists, and nurses. To examine knowledge, practice, and potential barriers to pharmacovigilance-related practices and adverse drug reaction reporting, a 22-item validated questionnaire was used. Results: The final analysis included 311 healthcare professionals. Most healthcare professionals, 59% (N = 182), mentioned encountering patients with adverse drug reactions during the last year. On the other hand, most healthcare professionals, 54% (n = 167), mentioned that they had not reported adverse drug reactions. A good proportion of respondents mentioned that it is essential to report adverse drug reactions (N = 288, 92.6%), availability of adverse drug reactions reporting forms in practice sites (N = 216, 69.5%), had awareness regarding how to report adverse drug reactions (N = 221, 71.1%), the necessity of reporting minor/less important adverse drug reactions (N = 265, 85.2%), and were trained on how to report adverse drug reactions (N = 201, 64.6%). Adverse drug reaction reporting program in the United Arab Emirates (N = 148, 47.6) was known to many healthcare professionals. Lack of time was the major impediment to reporting adverse drug reactions at 42.7% (N = 133). The predictor variable work experience does add to the model (p < 0.05) concerning association with filling of adverse drug reaction forms (Estimate = 0.380; SE = 0.452; p = 0.400), professional role (Estimate = 0.454; SE = 0.673; p = 0.500). In addition, the predictor variable practice setting adds to the model (p < 0.05) concerning the knowledge regarding the availability of adverse drug reaction reporting forms (Estimate = -1.229; SE = 0.298; p = 0.000), training on how to report adverse drug reactions (Estimate = -0.660; SE = 0.294; p = 0.025), and awareness regarding the adverse drug reaction reporting program in the United Arab Emirates (Estimate = -1.032; SE = 0.280; p = 0.000). Conclusion: Pharmacists had the most knowledge regarding adverse drug reaction reporting and pharmacovigilance. The underreporting of adverse drug reactions was documented among physicians and nurses. Lack of time was the most significant barrier to reporting adverse drug reactions, followed by uncertainty and complicated adverse drug reaction documentation forms.

Safety of cardiovascular disease drugs approved between 2014 and 2021 in the US: a pharmacovigilance analysis.

BACKGROUND: Recently FDA-approved drugs for cardiovascular disease (CVD) require robust post-marketing surveillance. The objective of this study was to assess their safety using a large pharmacovigilance database. RESEARCH DESIGN AND METHODS: We analyzed adverse event (AE) reports for 17 drugs approved from 2014 to 2021, utilizing the FDA Adverse Event Reporting System (FAERS). Descriptive and disproportionality analyses were conducted by estimating the reporting odds ratio (ROR) and its 95% confidence interval. RESULTS: Among the 43,664,773 AE reports 97,702 (0.22%) were related to newly approved CVD drugs. No AEs were reported for finerenone and evinacumab. The results from the disproportionality analyses revealed potential risks of acute kidney injury (ROR = 8.24, 95% CI: 6.05-11.22), cardiac failure (ROR = 4.80, 95% CI: 3.82-6.05), and hypotension (ROR = 3.98, 95% CI: 3.44-4.61) among sacubitril/valsartan users. Additionally, ivabradine was found to be associated with tachycardia (ROR = 11.94, 95% CI: 8.35-17.08), abnormal feeling (ROR = 4.40, 95% CI: 2.70-7.18), and dizziness (ROR = 2.56, 95% CI: 1.68-3.90). CONCLUSIONS: This study identified specific safety concerns related to recently approved CVD drugs. Further research is required to understand the underlying mechanisms and clinical implications of these findings.

A Pilot, Predictive Surveillance Model in Pharmacovigilance Using Machine Learning Approaches.

INTRODUCTION: The identification of a new adverse event (AE) caused by a drug product is one of the key activities in the pharmaceutical industry to ensure the safety profile of a drug product. Machine learning (ML) has the potential to assist with signal detection and supplement traditional pharmacovigilance (PV) surveillance methods. This pilot ML modeling study was designed to detect potential safety signals for two AbbVie products and test the model's capability of detecting safety signals earlier than humans. METHODS: Drug X, a mature product with post-marketing data, and Drug Y, a recently approved drug in another therapeutic area, were selected. Gradient boosting-based ML approaches (e.g., XGBoost) were applied as the main modeling strategy. RESULTS: For Drug X, eight true signals were present in the test set. Among 12 potential new signals generated, four were true signals with a 50.0% sensitivity rate and a 33.3% positive predictive value (PPV) rate. Among the remaining eight potential new signals, one was confirmed as a signal and detected six months earlier than humans. For Drug Y, nine true signals were present in the test set. Among 13 potential new signals generated, five were true signals with a 55.6% sensitivity rate and a 38.5% PPV rate. Among the remaining eight potential new signals, none were confirmed as true signals upon human review. CONCLUSION: This model demonstrated acceptable accuracy for safety signal detection and potential for earlier detection when compared to humans. Expert judgment, flexibility, and critical thinking are essential human skills required for the final, accurate assessment of adverse event cases.

Risk of dementia and Alzheimer's disease associated with antidiabetics: A Bayesian network meta-analysis.

INTRODUCTION: Dementia risk is substantially elevated in patients with diabetes. However, evidence on dementia risk associated with various antidiabetic regimens is still limited. This study aims to comprehensively investigate the risk of dementia and Alzheimer's disease (AD) associated with various antidiabetic classes. METHODS: Cochrane Central Register of Controlled Trials, Embase, MEDLINE (PubMed) and Scopus were searched from inception to March 2024 (PROSPERO CRD 42022365927). Observational studies investigating dementia and AD incidences after antidiabetic initiation were identified. Bayesian network meta-analysis was performed to determine dementia and AD risks associated with antidiabetics. Preferred Reporting Items for Systematic Reviews-Network Meta-Analyses (PRISMA-NMA) guidelines were followed. Statistical analysis was performed and updated in November 2023 and March 2024, respectively. RESULTS: A total of 1,565,245 patients from 16 studies were included. Dementia and AD risks were significantly lower with metformin and sodium glucose co-transporter-2 inhibitors (SGLT2i). Metformin displayed the lowest risk of dementia across diverse antidiabetics, whereas α-glucosidase inhibitors demonstrated the highest risk. SGLT2i exhibited the lowest dementia risk across second-line antidiabetics. Dementia risk was significantly higher with dipeptidyl peptidase-4 inhibitor (DPP4i), metformin, sulfonylureas and thiazolidinediones (TZD) compared to SGLT2i in the elderly (≥ 75 years). Dementia risk associated with metformin was substantially lower, regardless of diabetic complication status or baseline A1C. DISCUSSION: Metformin and SGLT2i demonstrated lower dementia risk than other antidiabetic classes. Patient-specific factors may affect this relationship and cautious interpretation is warranted as metformin is typically initiated at an earlier stage with fewer complications. Hence, further large-scaled clinical trials are required.

Adverse events associated with immune checkpoint inhibitors in non-small cell lung cancer: a safety analysis of clinical trials and FDA pharmacovigilance system.

Objectives: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of non-small cell lung cancer (NSCLC). However, the application of ICIs can also cause treatment-related adverse events (trAEs) and immune-related adverse events (irAEs). This study was to evaluate both the irAEs and trAEs of different ICI strategies for NSCLC based on randomized clinical trials (RCTs). The study also examined real-world pharmacovigilance data from the Food and Drug Administration Adverse Event Reporting System (FAERS) regarding claimed ICI-associated AEs in clinical practice. Methods: Based on Pubmed, Embase, Medline, and the Cochrane CENTRAL, we retrieved RCTs comparing ICIs with chemotherapy drugs or with different ICI regimens for the treatment of NSCLC up to October 20, 2023. Bayesian network meta-analysis (NMA) was performed using odds ratios (ORs) with 95% credible intervals (95%CrI). Separately, a retrospective pharmacovigilance study was performed based on FAERS database, extracting ICI-associated AEs in NSCLC patients between the first quarter (Q1) of 2004 and Q4 of 2023. The proportional reports reporting odds ratio was calculated to analyze the disproportionality. Results: The NMA included 51 RCTs that involved a total of 26,958 patients with NSCLC. Based on the lowest risk of any trAEs, cemiplimab, tislelizumab, and durvalumab were ranked as the best. Among the agents associated with the lowest risk of grades 3-5 trAEs, tislelizumab, avelumab, and nivolumab were most likely to rank highest. As far as any or grades 3-5 irAEs are concerned, atezolizumab plus bevacizumab plus chemotherapy is considered the most safety option. However, it is associated with a high risk of grades 3-5 trAEs. As a result of FAERS pharmacovigilance data analysis, 9,420 AEs cases have been identified in 7,339 NSCLC patients treated with ICIs, and ICIs were related to statistically significant positive signal with 311 preferred terms (PTs), and comprehensively investigated and identified those AEs highly associated with ICIs. In total, 152 significant signals were associated with Nivolumab, with malignant neoplasm progression, death, and hypothyroidism being the most frequent PTs. Conclusion: These findings revealed that ICIs differed in their safety profile. ICI treatment strategies can be improved and preventive methods can be developed for NSCLC patients based on our results.

Post-marketing safety concerns with abrocitinib: a real-world pharmacovigilance analysis of the FDA adverse event reporting system.

BACKGROUND: Abrocitinib was newly approved for treatment of moderate-to-severe atopic dermatitis. The present study was to assess abrocitinib-related adverse events (AEs) using the Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS: Disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms, were employed to quantify the signals of abrocitinib-related AEs. RESULTS: A total of 3,177,744 reports of AEs were collected from the FAERS database, of which 1370 reports were identified with abrocitinib as the primary suspect drug. Abrocitinib-induced adverse events (AEs) occurred across 27 system organ classes (SOCs). A total of 68 preferred terms (PTs) with significant disproportionality, meeting the criteria of all four algorithms simultaneously, were identified. Unexpected significant AEs, such as increased blood cholesterol, venous embolism, hypoacusis, cellulitis, and tuberculosis, might also occur. The median onset time for abrocitinib-associated AEs was 182 days (interquartile range [IQR] 47-527 days). CONCLUSIONS: The results of this study were consistent with clinical observations. Additionally, unexpected safety signals for abrocitinib were identified, which provided supportive information for the safety profile of abrocitinib. Prospective clinical studies are warranted to validate these findings.

BERT-based language model for accurate drug adverse event extraction from social media: implementation, evaluation, and contributions to pharmacovigilance practices.

Introduction: Social media platforms serve as a valuable resource for users to share health-related information, aiding in the monitoring of adverse events linked to medications and treatments in drug safety surveillance. However, extracting drug-related adverse events accurately and efficiently from social media poses challenges in both natural language processing research and the pharmacovigilance domain. Method: Recognizing the lack of detailed implementation and evaluation of Bidirectional Encoder Representations from Transformers (BERT)-based models for drug adverse event extraction on social media, we developed a BERT-based language model tailored to identifying drug adverse events in this context. Our model utilized publicly available labeled adverse event data from the ADE-Corpus-V2. Constructing the BERT-based model involved optimizing key hyperparameters, such as the number of training epochs, batch size, and learning rate. Through ten hold-out evaluations on ADE-Corpus-V2 data and external social media datasets, our model consistently demonstrated high accuracy in drug adverse event detection. Result: The hold-out evaluations resulted in average F1 scores of 0.8575, 0.9049, and 0.9813 for detecting words of adverse events, words in adverse events, and words not in adverse events, respectively. External validation using human-labeled adverse event tweets data from SMM4H further substantiated the effectiveness of our model, yielding F1 scores 0.8127, 0.8068, and 0.9790 for detecting words of adverse events, words in adverse events, and words not in adverse events, respectively. Discussion: This study not only showcases the effectiveness of BERT-based language models in accurately identifying drug-related adverse events in the dynamic landscape of social media data, but also addresses the need for the implementation of a comprehensive study design and evaluation. By doing so, we contribute to the advancement of pharmacovigilance practices and methodologies in the context of emerging information sources like social media.

Global trends in pharmacovigilance-related events: a 30-year analysis from the 2019 global burden of disease study.

BACKGROUND: Establishing effective pharmacovigilance systems globally is challenging due to the need for comprehensive epidemiological data on pharmacovigilance-related events, particularly in countries at different stages of development. AIM: This study aimed to determine magnitude and drivers of change in the global and regional burden of pharmacovigilance-related events from 1990 to 2019, analyzing variations between age groups and sex, providing data support for policymakers to adjust their pharmacovigilance policies. METHOD: Pharmacovigilance-related events were defined as Adverse Effects of Medical Treatment (AEMT) and Drug Use Disorders (DUD) in the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. Time trend analysis utilized joinpoint regression, age-period-cohort model, and decomposition method. Disease burden was measured in incidence, deaths, and disability-adjusted life years (DALYs). RESULTS: The global burden of pharmacovigilance-related events remained high, driven predominantly by population growth. Children and older adults were identified as particularly susceptible groups. Across various regions and periods of the socio-demographic index (SDI), the risk of death from AEMT showed a decreasing trend. In contrast, the incidence of AEMT and both the incidence and death rates from DUD showed a stable or worsening trend. Significant regional disparities in the burden of these diseases were noted between different SDI levels. CONCLUSION: The study underscores the critical need for robust pharmacovigilance systems worldwide. The observed trends in the burden of pharmacovigilance-related events offer a clear direction for countries to refine and strengthen their pharmacovigilance policies and practices.

Suspected Cutaneous Allergic Reactions with Ayurveda Medicine Punaranava Mandura: A Case Report.

INTRODUCTION: With the increasing use of traditional medicine, there is a need to be vigilant in identifying and reporting adverse reactions associated with them. Punarnava Mandura is a commonly used Ayurvedic medicine for the treatment of anemia. It is well tolerated by the patients. To our knowledge, allergic reactions to Punarnava Mandura have not been reported in the literature. We reported a case of adverse cutaneous reaction, which was probably associated with Purnarnava Mandura. CASE PRESENTATION: A 60-year-old female patient developed skin rashes over her neck region after taking Punarnava Mandura and other drugs for osteoarthritis. She recovered upon withdrawal of all the medicines and treatment with anti-allergic drugs. The patient re-initiated treatment for joint pain except for Punarnava Mandura and completed the course without a recurrence of the event making the Punarnava Mandura the culprit drug. CONCLUSION: Punarnava Mandura may cause allergic reactions, and clinicians should keep such adverse reactions in mind when using traditional medicine and report them to increase the scientific literature in this area.

Comparison of QTc interval changes in drug-resistant tuberculosis patients on delamanid-containing regimens versus shorter treatment regimens.

BACKGROUND: Delamanid (DLM) is a relatively new drug for drug-resistant tuberculosis (DR-TB) that has been used in Indonesia since 2019 despite its limited safety data. DLM is known to inhibit hERG potassium channel with the potential to cause QT prolongation which eventually leads to Torsades de pointes (TdP). OBJECTIVE: This study aims to analyse the changes of QTc interval in DR-TB patients on DLM regimen compared to shorter treatment regimens (STR). METHODS: A retrospective cohort was implemented on secondary data obtained from two participating hospitals. The QTc interval and the changes in QTc interval from baseline (ΔQTc) were assessed every 4 weeks for 24 weeks. RESULTS: The maximum increased of QTc interval and ΔQTc interval were smaller in the DLM group with mean difference of 18,6 (95%CI 0.3 to 37.5) and 31.6 milliseconds (95%CI 14.1 to 49.1) respectively. The proportion of QTc interval prolongation in DLM group were smaller than STR group (RR=0.62; 95%CI 0.42 to 0.93). CONCLUSION: This study has shown that DLM regimens are less likely to increase QTc interval compared to STR. However, close monitoring of the risk of QT interval prolongation needs to be carried out upon the use of QT interval prolonging antituberculoid drugs.

Predicted concentrations of antineoplastic drugs in the aquatic environment: The case of Ría de Vigo (NW, Spain).

The European Medicines Agency (EMA) mandates Environmental Risk Assessments (ERAs) since 2006 to determine potential risks of new marketed medicines. Drugs with a Predicted Environmental Concentration (PEC) in inland surface waters exceeding 0.01 µg L-1 require further environmental risk assessment. PEC may be refined based on prevalence data and/or based on the treatment regimen. In this study, based on EMA regulations, refined PEC of 108 antineoplastic drugs in coastal waters were determined based on the consumption in a coastal health area during 2021, identifying six drugs with potential environmental risk in surface waters (hydroxyurea, capecitabine, abiraterone, ibrutinib, imatinib and 5-fluorouracil) and two in marine ecosystem (hydroxyurea and capecitabine). Comparison of these refined PECs with data from marketing laboratories revealed significant disparities, suggesting the need for regular updates, especially with changes in drug indications or financing. Notably, the identified drugs are not yet on the main reference lists of emerging contaminants.

Prediction of adverse drug reactions in geriatric patients admitted to intensive care units.

INTRODUCTION: Intensive care units (ICUs) pose challenges in managing critically ill patients with polypharmacy, potentially leading to adverse drug reactions (ADRs), particularly in the elderly. OBJECTIVE: To evaluate whether the severity and clinical prognosis scores used in ICUs correlate with the prediction of ADRs in aged patients admitted to an ICU. METHODS: A cohort study was conducted in a Brazilian University Hospital ICU. APACHE II and SAPS 3 assessed clinical prognosis, while GerontoNet ADR Risk Score and BADRI evaluated ADR risk at ICU admission. Severity of the patients' clinical conditions was evaluated daily based on the SOFA score. ADR screening was performed daily through the identification of ADR triggers. RESULTS: 1295 triggers were identified (median 30 per patient, IQR=28), with 15 suspected ADRs. No correlation was observed between patient severity and ADRs at admission (p=0.26), during hospitalization (p=0.91), or at follow-up (p=0.77). There was also no association between death and ADRs (p=0.28) or worse prognosis and ADRs (p>0.05). Higher BADRI scores correlated with more ADRs (p=0.001). CONCLUSIONS: These data suggest that employing the severity and clinical prognosis scores used in ICUs is not sufficient to direct active pharmacovigilance efforts, which are therefore indicated for critically ill patients.

A real-world pharmacovigilance analysis of the FDA adverse event reporting system events for polatuzumab vedotin.

BACKGROUND: Polatuzumab vedotin is the first antibody-drug conjugate approved by the US Food and Drug Administration (FDA) for patients with diffuse large B-cell lymphoma. This study evaluated adverse events (AEs) associated with polatuzumab vedotin by data mining of the FDA Adverse Event Reporting System (FAERS). METHODS: This study included AEs registered in FAERS between 2019 Q2 and 2023 Q2. Four algorithms were used to quantify the signals of polatuzumab vedotin-associated AEs, including reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker. RESULTS: A total of 7,609,450 reports were collected from the FAERS database, and 1,388 reports of polatuzumab vedotin were identified as primary suspected AEs. Polatuzumab vedotin-associated AEs involved 26 organ systems. According to the four algorithms, 108 significant disproportionality AEs were retained simultaneously. Unexpected significant AEs included gastrointestinal hemorrhage, ileus, gastrointestinal perforation, cholecystitis, hypogammaglobulinemia, hepatitis B reactivation, hypercalcemia, hydronephrosis, cystitis hemorrhagic, interstitial lung disease, and thrombophlebitis. The median time to onset of polatuzumab vedotin-associated AEs was 20 (interquartile range 4-56) days. CONCLUSIONS: Our study identified significant new AE signals for polatuzumab vedotin through real-world disproportionality analysis data and may provide additional evidence for risk identification of polatuzumab vedotin.

Development, assessment and educational impact of a blended e-learning training program on pharmacovigilance implemented in four African countries.

Introduction: Efforts to improve medication access in low-and middle-income countries, particularly in Sub-Saharan Africa, have made progress, especially in the fight against infectious diseases such as tuberculosis. However, challenges exist in establishing effective pharmacovigilance systems. The PhArmacoVIgilance Africa (PAVIA) project was committed to enhancing pharmacovigilance in Tanzania, Eswatini, Nigeria, and Ethiopia, with an emphasis on anti-tuberculosis drugs, utilizing various methods, including training. This study evaluates the PAVIA training program's effectiveness and its adaptation during the COVID-19 pandemic. Methods: A blended e-learning program, incorporating two courses and a platform for educational materials, was developed. This program, designed to train healthcare professionals in pharmacovigilance, was incorporated into a Training of Trainers model. To evaluate the program effectiveness, we used multiple measures such as assessing knowledge gain through pre-and post-test scores, assessing learners' satisfaction and attitudes via questionnaires, and analyzing Individual Case Safety Reports (ICSRs) in VigiBase to determine the impact on spontaneous reporting systems in the PAVIA countries. Results: 121 learners enrolled in the pilot trainings, including 36 from Tanzania, 34 from Eswatini, 25 from Nigeria, and 26 from Ethiopia. Notably, post-test scores were significantly higher than pre-test scores in all four countries. Following the pilot trainings, multiple step-down training sessions were held in Tanzania, Eswatini, and Nigeria, with a total of 827 learners registering and 421 successfully completing the program. Learners' scores on the post-tests were significantly higher than on the pre-tests for both courses in all three countries. Learners' feedback on the training was overwhelmingly positive. Additionally, a qualitative analysis of ICSRs revealed a substantial increase in reports after the training in Tanzania, Eswatini, and Nigeria. Discussion: An innovative e-learning program trained healthcare professionals in pharmacovigilance and anti-tuberculosis drug safety over 3 years in four PAVIA countries. The program effectively improved participants' knowledge, received positive feedback, and likely had an impact on reporting rates in Tanzania, Eswatini, and Nigeria, although a direct causal link could not be definitively established due to data limitations and other factors, such as the heightened reporting rates associated with COVID-19 vaccines, that could have contributed to the notable increase in ICSRs.

Toxicity burden patterns of MET-selective tyrosine kinase inhibitors: evidence from real-world pharmacovigilance.

MET exon 14 skipping alterations and MET amplifications are recognized as oncogenic and targetable genetic changes in cancer patients. The treatment of MET-selective tyrosine kinase inhibitors (TKIs) in this specific population has shown encouraging therapeutic results. However, a comprehensive understanding of the potential toxicities linked to these agents is still lacking. The present pharmacovigilance analysis was carried out using the FDA Adverse Event Reporting System database to assess notable adverse events associated with MET-selective TKIs. Gastrointestinal disorders, respiratory toxicity, hepatotoxicity, and disturbances in metabolism and nutrition demonstrated a substantial prevalence and significance among the adverse event (AE) categories. Particularly notable were the occurrences of peripheral oedema, nausea, dysphagia, fatigue, and dyspnoea, which emerged as the foremost five reported AEs. The majority of these AEs were observed within the initial months of initiating treatment with MET-selective TKIs and persistently thereafter. Notably, our investigation unveiled a significant correlation between the usage of capmatinib and the incidence of hearing loss and difficulty in swallowing. Diligent monitoring and the implementation of supportive care strategies are essential in managing the toxicities associated with MET-selective TKIs, particularly those related to gastrointestinal disorders, respiratory toxicity, hepatotoxicity, and ototoxicity.

Adverse events following Covaxin administration among adolescents (15-18 years) - A pharmacovigilance study in a district in Northern India.

Introduction: The study was undertaken to observe the adverse event following immunization (AEFI) to the Covaxin vaccine in young adolescents in the age group of 15-18 years in a district in Northern India. The study was conducted to assess the safety profile of the COVAXIN vaccine. Methodology: This was a prospective observational study conducted at rural and urban health centers of a district in Northern India. We included the beneficiaries of the COVAXIN between the age of 15 and 18 years. The administration of the COVAXIN occurred in our district from January 2022. Periodic visits were conducted to the urban and rural health centers of the city to record any suspected adverse drug reaction following immunization in the defined population. The study was conducted for a period of 1 year (January 2022 to December 2022). Results: A total of 72,771 adolescents (15-18 years) received the first dose of Covaxin and 49,046 received the second dose. No adverse drug event following immunization was reported during the study. Conclusion: Thus, it can be concluded that Covaxin was found to be safe in adolescents (15-18 years).