Drug Safety Research Articles

Gauging Expert Perspectives: A Survey on AI Integration in Pharmacovigilance

Abstract: The ever-growing landscape of drug safety monitoring demands innovative solutions. This paper explores how Artificial Intelligence (AI) can revolutionize pharmacovigilance by enhancing patient safety and enabling personalized medicine. A survey conducted by the author indicates a positive outlook on AI's potential in this field. AI excels at analysing vast data sources, leading to improved detection of subtle safety signals and emerging drug safety concerns. Additionally, AI-powered risk prediction allows for personalized treatment strategies, minimizing adverse drug reactions for individual patients. Furthermore, AI facilitates efficient literature mining and drug repurposing, accelerating drug discovery processes. While the potential benefits are significant, responsible implementation is crucial. Addressing potential biases in algorithms and ensuring data privacy and security remain critical considerations. Overall, AI holds immense promise for the future of pharmacovigilance, paving the way for a more efficient, accurate, and proactive system for safeguarding patient well-being.

Upgrading of Quality Control for Herbal Medicine Use in South Korea by Introducing an Accreditation System: a brief report.

This study aimed to present a government-led accreditation system for upgrading the quality control of herbal medicine by introducing the process and evaluation standard of external herbal dispensaries (EHDs) of traditional Korean medicine (TKM) clinics in South Korea 2018 to refer to other countries where herbal medicine were used similarly in Korea. We organized an EHD accreditation committee for the establishment of an accreditation system. The committee consisted of 9 experts an official of the Ministry of Health and Welfare (MoHW), a professor expert of TKM, a good manufacturing practice expert, a hazard analysis and critical control point expert, and an accreditation system expert. After 3 meetings, a draft of the evaluation standard and evaluation system was established in 2017. Based on the draft, a pilot test was conducted to determine the applicability of the evaluation standards in 2017. Two additional meeting was held to confirm the accreditation standards and was finalized in 2018. The evaluation standard for EHDs was developed. In the case of herbal medicine EHDs, the evaluation standard consisted of 9 evaluation categories, 25 evaluation parts, and 81 evaluation items were developed. The results of the evaluation of the pilot tests are as follows, and the results show that there is a deviation between the EHDs. As a world's first, Korea MoHW successfully launched the accreditation system for upgrading the quality control system of herbal medicine not approved by Korea's Ministry of Food and Drug Safety in 2018. Our report hope to provide a good reference to other countries where having similar herbal medicine system in South Korea hoping to make better quality control of herbal medicines.

РАЗРАБОТКА И ВАЛИДАЦИЯ ЭЛЕКТРОННОЙ АНКЕТЫ ПО ОЦЕНКЕ ПРОФЕССИОНАЛЬНОЙ ИНФОРМИРОВАННОСТИ ВРАЧЕЙ О ПОРЯДКЕ СООБЩЕНИЙ О НЕЖЕЛАТЕЛЬНЫХ РЕАКЦИЯХ НА ЛЕКАРСТВЕННЫЕ ПРЕПАРАТЫ

Drug safety is one of the priority areas of modern medicine and pharmacy. The statistics and accounting of adverse drug reactions represent a complex problem due to the fact that many adverse reactions remain unrecognized and also depend on the willingness of healthcare professionals to inform regulatory authorities about the occurred adverse reactions. The objective of this study was to create and assess the reliability of an electronic questionnaire aimed at evaluating healthcare professionals' understanding of the procedures for reporting adverse drug reactions. The study consisted of two phases: the first phase focused on the development of the questionnaire and evaluation of a draft version by an expert committee, while the second phase included pilot testing with 30 respondents. The final version of the electronic questionnaire consists of 23 questions. As a result of the two phases of development and validation, the electronic questionnaire demonstrates sufficient reliability and validity, suggesting its potential for future use.

Stabilization of Arsenic and Heavy Metal Contaminated Soil Using Fishery By-Products and Evaluation of Heavy Metal Uptake in Crops

Objectives : Heavy metals eluted from mine waste pollute surrounding soil and water systems, which can spread to crops and have a harmful effect on the human body. The purpose of this study was to evaluate the feasibility of recycling discarded mussel shells(MS) and manila clam shells (MC) as stabilizers for the immobilization of arsenic(As) and heavy metals(Pb, Zn) in soil.Methods : MS and MC were processed with -#10 mesh natural material, -#20 mesh natural material, and -#10 mesh calcined material and treated at 0-10 wt%. After 1 week or 4 weeks of wet curing, it was eluted with 0.1 N HCl and the concentrations of As, Pb, and Zn in the soil were analyzed through inductively coupled plasma optical emission spectroscopy(ICP-OES) analysis. In addition, red lettuce was cultivated in the stabilized soil and the concentration of heavy metals that were transferred to crops was evaluated. The stabilization mechanism was investigated by scanning electron microscopy-energy dispersive X-ray spectroscopy(SEM-EDX) analysis.Results and Discussion : The stabilization efficiency for arsenic and heavy metals was in the order of natural -#10 mesh < natural -#20 mesh < calcined -#10 mesh. The calcined stabilizer showed a high stabilization efficiency of 98% at a 2 wt% treatment level. Pb was not detected in the red lettuce grown in the stabiliz ed soil, and the standard for leafy vegetables (Pb-0.3 mg/kg or less) was satisfied according to the Ministry of Food and Drug Safety. The SEM-EDX analysis revealed that As was stabilized through Ca-As precipitation and heavy metals(Pb, Zn) were stabilized through pozzolanic reactions.Conclusion : Stabilizers developed from MS and MC can be effectively applied to the stabilization of As and heavy metal-contaminated soil, and are expected to be used as economical and environmentally friendly stabilizers.

Efficacy and safety of first-line biological DMARDs in rheumatoid arthritis patients with chronic kidney disease

ObjectiveTo evaluate the efficacy and safety of first-line biological disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) with chronic kidney disease (CKD), including those undergoing haemodialysis (HD).MethodsThis retrospective...

Application of Antithrombotic Drugs in Patients with Acute Type B Aortic Dissection Underwent Thoracic Endovascular Aortic Repair.

This study aimed to evaluate the safety and necessity of antithrombotic drugs for acute type B aortic dissection (TBAD) treated with thoracic endovascular aortic repair (TEVAR).The patients of acute TBAD treated with TEVAR were retrospectively enrolled from January 2007 to October 2022 in General Hospital of Northern Theater Command. The primary outcomes such as mortality and aortic adverse events [stroke, paraplegia, limb ischemia, organ failure (renal and intestinal tract), endoleak, redissection, aortic rupture, reintervention, and mortality] were recorded and evaluated at 1 month (early term) and 18 months (late term).The 697 patients of TBAD treated with TEVAR were divided into the antithrombotic (AT) group (n = 208) and nonantithrombotic (NAT) group (n = 489). The incidence of early mortality, early aortic adverse events, and the 18 months of cumulative freedom from all-cause mortality and aortic adverse events were not significantly different between the AT and NAT groups (2.4% versus 1.4%, 2.9% versus 4.5%, 94.7% versus 96.5% and 88.4% versus 89.9%, respectively). Log-rank tests also indicated that there were no significant differences. In multivariate Cox regression models, only pleural effusion, partially thrombosed of false lumen, maximum diameter of false lumen, and branch involvement were independent predictors of mortality, whereas the systolic blood pressure (SBP), pleural effusion, partially thrombosed of false lumen, true lumen compression, maximum diameter of false lumen, branch involvement were independent predictors of adverse aortic events.The antithrombotic drug for acute TBAD treated with TEVAR does not influence the mortality and aortic events in the early and late terms.

Nano-theranostics: A novel platform in drug therapy

A fundamental component of customized medicine, theranostics is a therapy approach that combines therapeutics and diagnostics with the goal of increasing drug efficacy and safety while also monitoring treatment response. It will require significant advancements in predictive medicine. Theranostics is linked to tailored drug administration based on test results as well as a diagnostic that screens patients for potential adverse drug reactions. Early diagnosis and treatment have benefited from the designed nanoparticles with unique physicochemical characteristics. This allows treatments to be delivered and the detection method to be employed concurrently, not just before or after treatment but throughout the entire regimen. The development of nanotechnology presents more opportunities for theranostics applications using nanoparticle engineering, and it has demonstrated encouraging outcomes, particularly in cancer therapy when compared with conventional treatments.

STUDY OF PHYSICOCHEMICAL AND BIOLOGICAL PROPERTIES OF A NEW BISPIDINE WITH A MORPHOLINE FRAGMENT

The experimental results obtained during the work enrich modern medicinal chemistry with new information about the development and local anesthetic activity of a promising class of chemical compound - O-benzoyloxime of bispidine. The discovered new properties of the molecule can serve as the basis for the creation of a new domestic safe local anesthetic drug that is effective in models of infiltration and conduction anesthesia and has low toxicity. The aim of this work is to synthesize and study the physicochemical and biological properties of a new morpholino-substituted bispidine derivative. Results and discussion. 3-(3-(Ethan-1-yloxy)propyl)-7-[3-(morpholine-4-yl)propyl]-3,7-diazabicyclo[3.3.1]nonan-9-one was constructed in 56.9% yield. Oximation under the influence of a powerful oximylating agent led to the oxime. O-Benzoyloxime was synthesized by benzoylation of the oxime. The complex of O-benzoyloxime with β-cyclodextrin - LA-180 was studied for local anesthetic activity and acute toxicity. Conclusion. It was established that LA-180 manifested itself as a highly active compound in a series of experiments studying infiltration and conduction anesthesia. The results of a study of acute toxicity after a single subcutaneous administration to white outbred mice showed that LA-180 (925 mg/kg) is a low-toxic compound in comparison with standard drugs such as trimecaine, lidocaine and novocaine.

녹차 가공 과자류의 제품명 연구

This study was to analyze the product name of the green tea processed confectionery and identify the characteristics reflected in those names, thereby providing insights necessary for developing such product names. For this purpose, this study collected data on 427 confectionery items with product names containing ‘green tea’ by searching the processed food database on the Ministry of Food and Drug Safety website from June 1 to June 16, 2024. The main research findings from the collected data analysis are as follows. First, the structural characteristics of confectionery product names included the prevalence of combinations of Sino-Korean words and loanwords, the use of neologisms or native words, and the need for improvement in foreign language expressions. Second, the semantic characteristics of the product names revealed the rise of foreign-style baked goods, the application of diversified confectionery ingredients, and the emergence of high-protein and vegan confectionery. In conclusion, green tea processed confectionery products should be named carefully compared to other products, as their names play a crucial role in conveying a healthy image and influencing consumer choice.

ГЛОБАЛЬНАЯ БЕЗОПАСНОСТЬ БЕНРАЛИЗУМАБА: ФАРМАКОНАДЗОРНЫЙ АНАЛИЗ ДАННЫХ СПОНТАННЫХ СООБЩЕНИЙ

Ensuring drug safety is one of the key areas of modern medicine and pharmacy. Recent studies and publications confirm the long-term effectiveness and safety of using benralizumab. However, when making clinical decisions, it is important to consider the risks associated with biological therapy in order to provide adequate consultations for patients and effectively monitor potential adverse reactions. This article examines serious and significant adverse reactions associated with the use of benralizumab, as well as an analysis of the World Health Organization's global database, VigiBase, regarding adverse reactions to benralizumab. The data obtained on adverse reactions serve as a theoretical basis for improving the pharmacovigilance and drug monitoring system in Russia, presenting significant practical value for physicians, researchers, and healthcare professionals.

СИСТЕМНЫЙ АНАЛИЗ ПРИЧИН И ФАКТОРОВ НЕЖЕЛАТЕЛЬНЫХ РЕАКЦИЙ ПРИМЕНЕНИЯ ОМАЛИЗУМАБА

The article presents a systematic analysis of the causes and factors of adverse reactions to the use of omalizumab. Methods of monitoring appeals, expert assessment, and interviewing medical specialists were applied. The analysis showed that in Russia there is a "declarative passivity" of medical workers and patients in relation to reports of adverse reactions to the use of omalizumab, which is associated with a high workload and reluctance on the part of medical workers to issue a notification, lack of knowledge about the procedure for notification, fear of being punished for possible incorrect actions on the use of the drug; on the part of patients – by not knowing their rights and the procedure for submitting a report, by fear of spoiling relations with the attending physician. Such passivity and closeness hinders the formation of a system for the prevention of drug safety violations. The data obtained in the course of the study (on the frequency and structure of adverse reactions to the use of omalizumab in clinical practice in children and adults; information on the most dangerous combinations of omalizumab with other drugs; The characteristics of the causes and factors of adverse reactions to the use of omalizumab, as well as the untimely submission of notifications about them, have become the theoretical basis for the development of recommendations for improving pharmacovigilance activities to ensure the safety of the use of omalisamab in children and adults, which includes 4 areas: creation of organizational conditions to ensure the safety of the use of omalisamab in children and adults in medical organizations; prevention of adverse reactions to the use of omalizumab at the preclinical stage; optimization of clinical choice and support for decision-making by a medical specialist (doctor) when prescribing omalizumab based on a risk-based approach, taking into account the individual characteristics of the patient and the clinical situation; improving the quality of safety monitoring of the use of omalizumab.

Anaphylactic reaction to tranexamic acid infusion in a six-year-old child: a case report

BackgroundTranexamic acid (TXA) is commonly considered a safe drug to mitigate bleeding during and after various surgical settings among adults and children. In recent decades, anaphylaxis induced by TXA has been increasingly reported in adults. However, among pediatrics, there are fewer reported cases.Case presentationWe report a case of a 6-year-old female who experienced anaphylaxis after receiving intravenous TXA following unilateral cleft lip and palate repair surgery. She exhibited clinical symptoms involving the cardiovascular system, respiratory system, and skin. Following the administration of epinephrine, corticosteroid, and anti-histamine, the patient’s symptoms were relieved. A few months after discharge, an intradermal test, yielded a positive result, confirming TXA as the culprit drug.ConclusionOur report emphasizes the importance of considering anaphylaxis as a potential adverse reaction to TXA in pediatric patients, showing the criticality of rapid diagnosis and appropriate management for a successful outcome.

Preliminary antifibrotic and vasoconstrictor effects of adrenaline in Schlemm's canal and suprachoroidal minimally invasive glaucoma surgery in primary open-angle glaucoma.

To investigate the antifibrotic and vasoconstrictor effects of adrenaline in Schlemm's canal and suprachoroidal minimally invasive glaucoma surgery (MIGS). Human trabecular meshwork (TM) cells were treated with different concentrations of adrenaline (0%, 0.0005%, 0.01%), and we measured the effects on contractility, cell viability and the expression of key cell cycle and fibrosis genes. Adrenaline 0.05% was also injected intracamerally in five primary open-angle glaucoma patients undergoing iStent inject or MINIject surgery combined with phacoemulsification. All patients were assessed for ocular and systemic adverse reactions, including the effects on intraoperative pupil size, preoperative and postoperative visual acuity, intraocular pressure, and anterior segment OCT results. Adrenaline significantly reduced the contractility of TM cells in a dose-dependent manner (87.8%, 80.6%, 7.9% matrix contraction with adrenaline 0%, 0.0005%, 0.01%, respectively). Adrenaline did not exhibit any significant cytotoxicity even at high concentrations (P > 0.05). Adrenaline 0.01% significantly downregulated the expression of key cell cycle genes in the G2 and M phases, and also decreased the expression of MRTFB and ACTA2 genes (P < 0.05). Intracameral injections of adrenaline 0.05% in the five MIGS patients did not result in any ocular or systemic adverse effects. We recommend intracameral injections of adrenaline 0.05% as a cheap and safe drug to be used before MIGS insertion. Adrenaline decreases the risk of bleeding from the trabecular meshwork and also exhibits antifibrotic effects by arresting the cell cycle, thereby increasing the postoperative success rates in MIGS. What is known Fibrosis is the main cause of surgical failure in minimally invasive glaucoma surgery (MIGS). Mitomycin-C and 5-fluorouracil are too toxic to be used inside the eye. What is new Adrenaline reduced the contractility of trabecular meshwork cells and inhibited the expression of key cell cycle genes and fibrosis genes, without significant cytotoxicity. Intracameral injection of adrenaline 0.05% did not result in any ocular or systemic adverse reactions in MIGS patients.

Association Between Vedolizumab Treatment and Arthritis/Arthralgia in Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

Vedolizumab is a humanized gut selective drug that targets α4β7 integrin and has been used successfully in the treatment of inflammatory bowel disease (IBD). Pivotal studies have already demonstrated the drug's safety, but some real-life cohorts have shown an increase in arthralgia and arthritis in patients using vedolizumab. These findings raised the question of whether these joint symptoms are extraintestinal manifestations of IBD (since the drug acts only in the gut) or if they are associated with the use of vedolizumab. This systematic review and meta-analysis aimed to assess the incidence of arthralgia/arthritis in patients receiving vedolizumab and to investigate whether these events are indeed drug related. Pubmed, Cochrane, and Scopus were searched for randomized clinical trials reporting the incidence of joint manifestations in patients with Crohn's disease (CD) or ulcerative colitis (UC) who were treated with vedolizumab. The considered outcomes were arthritis and arthralgia. We used RevMan to calculate the pooled incidence of the reported outcomes and their corresponding 95% confidence intervals (95% CI). The search strategy yielded 4,206 articles. After removal of duplicates and screening of results, 6 randomized studies met the inclusion criteria. A total of 3,134 patients with moderately to severe IBD were included. Of those, 2,119 were randomized to receive vedolizumab and 1,015 to placebo. In the intervention group, 210 patients developed arthritis or arthralgia of any kind while 84 patients developed those symptoms in the placebo group (RR=1.09; 95%CI: 0.86-1.38; p=0.49, I2=0%), showing no significant association. Results also showed no significant association between exposure and the studied outcome after comparing CD (RR=1.02; 95%CI: 0.76-1.37, p=0.89, I2=0%) and UC (RR=1.24; 95%CI: 0.81-1.89, p=0.32, I2=43%) separately. The meta-analysis showed no association of these symptoms to the treatment with vedolizumab. Therefore, the new onset of worsening arthritis and arthralgia may be associated with the course of the disease itself, with the body's response to the drugs or with the exclusion of corticosteroids or anti-TNF from concomitant treatment with vedolizumab. Further studies with larger sample sizes are required, especially randomized clinical trials comparing anti-TNF, corticosteroid and immunomodulators to evaluate the incidence of joint manifestations in patients with IBD and even other rheumatological manifestations that may be associated as well.

Pharmacotherapy of older and senile patients. Review

Drug therapy of older and senile patients has several features due to age-related changes in the pharmacokinetics and pharmacodynamics of drugs, as well as the nature of the development and course of the disease. Age-related changes in drug pharmacodynamics, and increased or decreased sensitivity to drugs of different pharmacotherapeutic groups significantly affect the drug effectiveness and safety in the body. These peculiarities must be considered when prescribing pharmacotherapy for elderly and senile patients, and adjusting doses and regimens of drug administration. Morbidity in older people is characterised by a high level of polymorbidity and polypharmacy caused by it. When prescribing medicine to older patients, it has to observe all indications and contraindications. The drug interaction problem, which can increase the side effects risk, requires special attention under the conditions of age-related polymorbidity and polypharmacy. To optimise the metabolism and functions of the body, it is advisable to include metabolic therapy drugs in the older patients' complex therapy. Adherence to the rules for prescribing medicines according to the age-related features of their action is an important prerequisite for rational pharmacotherapy of older and senile patients. _________________________________________________________________________________________ Keywords: pharmacotherapy in ageing; pharmacokinetics; drug pharmacodynamics; polymorbidity; polypharmacy

Synergistic effects of calcium channel blockers and renin-angiotensin inhibitors with gemcitabine-based chemotherapy on the survival of patients with pancreatic cancer

PurposePancreatic cancer remains a significant public health challenge, with poor long-term outcomes due to the lack of effective treatment options. Repurposing commonly used clinical drugs, such as ACE inhibitors, ARBs, CCBs, and metformin, may enhance the efficacy of chemotherapy and offer a promising therapeutic strategy for improving patient outcomes.MethodsA retrospective analysis of concomitant treatment with ACE-Is, ARBs, CCBs, and metformin alongside gemcitabine chemotherapy in patients with pancreatic cancer was conducted. Treatment responses were evaluated, with overall survival (OS) estimated using the Kaplan–Meier method. Additionally, the Cox proportional hazards model was employed to assess the impact of these specific agents on patient survival.Results4628 patients with various stages of pancreatic cancer were identified in the database between 2007 and 2016. The estimated overall survival (OS) in the analyzed group was 6.9 months (95% CI 6.4–7). The use of any of the analyzed drugs was associated with a significant improvement in mOS of 7.5 months (95% CI 6.8–7.8) vs. 6.7 months (95% CI 6.4–7.0) for patients who did not have additional treatment (p < 0.0001). ARBs, ACE-Is, CCBs, and metformin varied in their effectiveness in prolonging mOS among patients. The longest mOS of 8.9 months (95% CI 7.7–11.6) was observed in patients receiving additional therapy with ARBs, while the shortest mOS of 7.7 months (95% CI 6.5–8.9) was achieved by patients receiving metformin. In the adjusted Cox analysis, metformin was associated with a significantly weaker effect on mOS (p = 0.029). A particularly interesting trend in prolonging 5-year survival was demonstrated by ARBs and CCBs with 14.1% (95% CI 9–22%) and 14.8% (95% CI 11.1–19.6%), respectively, compared to patients not taking these drugs, who achieved a 5-year OS of 3.8% (95% CI 3.2–4.4%).ConclusionOur results demonstrate a significant positive impact of ARBs, ACE inhibitors, and CCBs on survival in patients with pancreatic cancer treated with gemcitabine. The addition of these inexpensive and relatively safe drugs in patients with additional comorbidities may represent a potential therapeutic option in this indication. However, prospective clinical trials to evaluate the optimal patient population and further studies to determine the potential impact of these agents on chemotherapy are necessary.

Developing large language models to detect adverse drug events in posts on X

ABSTRACT Adverse drug events (ADEs) are one of the major causes of hospital admissions and are associated with increased morbidity and mortality. Post-marketing ADE identification is one of the most important phases of drug safety surveillance. Traditionally, data sources for post-marketing surveillance mainly come from spontaneous reporting system such as the Food and Drug Administration Adverse Event Reporting System (FAERS). Social media data such as posts on X (formerly Twitter) contain rich patient and medication information and could potentially accelerate drug surveillance research. However, ADE information in social media data is usually locked in the text, making it difficult to be employed by traditional statistical approaches. In recent years, large language models (LLMs) have shown promise in many natural language processing tasks. In this study, we developed several LLMs to perform ADE classification on X data. We fine-tuned various LLMs including BERT-base, Bio_ClinicalBERT, RoBERTa, and RoBERTa-large. We also experimented ChatGPT few-shot prompting and ChatGPT fine-tuned on the whole training data. We then evaluated the model performance based on sensitivity, specificity, negative predictive value, positive predictive value, accuracy, F1-measure, and area under the ROC curve. Our results showed that RoBERTa-large achieved the best F1-measure (0.8) among all models followed by ChatGPT fine-tuned model with F1-measure of 0.75. Our feature importance analysis based on 1200 random samples and RoBERTa-Large showed the most important features are as follows: “withdrawals”/”withdrawal”, “dry”, “dealing”, “mouth”, and “paralysis”. The good model performance and clinically relevant features show the potential of LLMs in augmenting ADE detection for post-marketing drug safety surveillance.

Drug-Induced Mitochondrial Disruption in the Blood-Brain Barrier Cells: Overlooked Player in Drug Safety Evaluation.

The blood-brain barrier (BBB) is based on the unique pattern of the microvasculature of the central nervous system (CNS), which controls the transport of molecules between the CNS and the blood. The blood-brain barrier is mainly composed of endothelial cells, pericytes, and basement membrane, as well as the astrocytes and immune cells as perivascular macrophages and microglial cells. The dysfunction of this barrier can cause serious neuronal disorders due to the transport of hazardous molecules and immune cells to the CNS. Mitochondria plays a major role in cellular homeostasis in terms of health and disease. This review evaluated the published data about the effect of the drugs on the cells of BBB. Only seven articles were found that considered the effect of drugs on the barrier endothelial cells and mitochondria via different assays. Further studies are recommended to evaluate the impact of used medications on BBB cell bioenergetics. Also, the effect of the newly studied pharmaceutical agents on the BBB bioenergetics should be included within their safety profile studies.

Safeguarding Patients in the AI Era: Ethics at the Forefront of Pharmacovigilance.

Artificial intelligence is increasingly being used in pharmacovigilance. However, the use of artificial intelligence in pharmacovigilance raises ethical concerns related to fairness, non-discrimination, compliance, and responsibility as the central ethical principles in risk assessment and regulatory requirements. This paper explores these concerns and provides a roadmap to how to address these challenges by considering data collection, privacy protection, transparency and accountability, model training, and explainability in artificial intelligence decision making for drug safety surveillance. A number of responsible approaches have been identified including an ethics framework and best practices to enhance artificial intelligence use in healthcare. The document also recognizes some initiatives that have demonstrated the importance of ethics in artificial intelligence pharmacovigilance. Nevertheless, the major needs mentioned in this paper are transparency, accountability, data protection, and fairness, which stress the necessity of collaboration to construct a cognitive framework aimed at integrating ethical artificial intelligence into pharmacovigilance. In conclusion, innovation should be balanced with ethical responsibility to enhance public health outcomes as well as patient safety.

Drug-induced torsadogenicity prediction model: An explainable machine learning-driven quantitative structure-toxicity relationship approach

Drug-induced Torsade de Pointes (TdP), a life-threatening polymorphic ventricular tachyarrhythmia, emerges due to the cardiotoxic effects of pharmaceuticals. The need for precise mechanisms and clinical biomarkers to detect this adverse effect presents substantial challenges in drug safety assessment. In this study, we propose that analyzing the physicochemical properties of pharmaceuticals can provide valuable insights into their potential for torsadogenic cardiotoxicity. Our research centers on estimating TdP risk based on the molecular structure of drugs. We introduce a novel quantitative structure-toxicity relationship (QSTR) prediction model that leverages an in silico approach developed by adopting the 4R rule in laboratory animals. This approach eliminates the need for animal testing, saves time, and reduces cost. Our algorithm has successfully predicted the torsadogenic risks of various pharmaceutical compounds. To develop this model, we employed Support Vector Machine (SVM) and ensemble techniques, including Random Forest (RF), Extreme Gradient Boosting (XGBoost), and Categorical Boosting (CatBoost). We enhanced the model's predictive accuracy through a rigorous two-step feature selection process. Furthermore, we utilized the SHapley Additive exPlanations (SHAP) technique to explain the prediction of torsadogenic risk, particularly within the RF model. This study represents a significant step towards creating a robust QSTR model, which can serve as an early screening tool for assessing the torsadogenic potential of pharmaceutical candidates or existing drugs. By incorporating molecular structure-based insights, we aim to enhance drug safety evaluation and minimize the risks of drug-induced TdP, ultimately benefiting both patients and the pharmaceutical industry.