Drug Safety最新文献

{"title":"Pharmacovigilance in Pregnancy Studies, Exposures and Outcomes Ascertainment, and Findings from Low- and Middle-Income Countries: A Scoping Review.","authors":"Jenine Shafi, Maneet K Virk, Emma Kalk, James G Carlucci, Audrey Chepkemoi, Caitlin Bernard, Megan S McHenry, Edwin Were, John Humphrey, Mary-Ann Davies, Ushma C Mehta, Rena C Patel","doi":"10.1007/s40264-024-01445-1","DOIUrl":"10.1007/s40264-024-01445-1","url":null,"abstract":"<p><strong>Introduction: </strong>Pharmacovigilance (PV), or the ongoing safety monitoring after a medication has been licensed, plays a crucial role in pregnancy, as clinical trials often exclude pregnant people. It is important to understand how pregnancy PV projects operate in low- and middle-income countries (LMICs), where there is a disproportionate lack of PV data yet a high burden of adverse pregnancy outcomes. We conducted a scoping review to assess how exposures and outcomes were measured in recently published pregnancy PV projects in LMICs.</p><p><strong>Methods: </strong>We utilized a search string, secondary review, and team knowledge to review publications focusing on therapeutic or vaccine exposures among pregnant people in LMICs. We screened abstracts for relevance before conducting a full text review, and documented measurements of exposures and outcomes (categorized as maternal, birth, or neonatal/infant) among other factors, including study topic, setting, and design, comparator groups, and funding sources.</p><p><strong>Results: </strong>We identified 31 PV publications spanning at least 24 LMICs, all focusing on therapeutics or vaccines for infectious diseases, including HIV (n = 17), tuberculosis (TB; n = 9), malaria (n = 7), pertussis, tetanus, and diphtheria (n = 1), and influenza (n = 3). As for outcomes, n = 15, n = 31, and n = 20 of the publications covered maternal, birth, and neonatal/infant outcomes, respectively. Among HIV-specific publications, the primary exposure-outcome relationship of focus was exposure to maternal antiretroviral therapy and adverse outcomes. For TB-specific publications, the main exposures of interest were second-line drug-resistant TB and isoniazid-based prevention therapeutics for pregnant people living with HIV. For malaria-specific publications, the primary exposure-outcome relationship of interest was antimalarial medication exposure during pregnancy and adverse outcomes. Among vaccine-focused publications, the exposure was assessed during a specific time during pregnancy, with an overall interest in vaccine safety and/or efficacy. The study settings were frequently from Africa, designs varied from cohort or cross-sectional studies to clinical trials, and funding sources were largely from high-income countries.</p><p><strong>Conclusion: </strong>The published pregnancy PV projects were largely centered in Africa and concerned with infectious diseases. This may reflect the disease burden in LMICs but also funding priorities from high-income countries. As the prevalence of non-communicable diseases increases in LMICs, PV projects will have to broaden their scope. Birth and neonatal/infant outcomes were most reported, with fewer reporting on maternal outcomes and none on longer-term child outcomes; additionally, heterogeneity existed in definitions and ascertainment of specific measures. Notably, almost all projects covered a single therapeutic exposure, missing an opportunity to leverage the","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11399196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141436684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and Effectiveness of COVID-19 Vaccines During Pregnancy: A Living Systematic Review and Meta-analysis.","authors":"Agustín Ciapponi, Mabel Berrueta, Fernando J Argento, Jamile Ballivian, Ariel Bardach, Martin E Brizuela, Noelia Castellana, Daniel Comandé, Sami Gottlieb, Beate Kampmann, Agustina Mazzoni, Edward P K Parker, Juan M Sambade, Katharina Stegelmann, Xu Xiong, Andy Stergachis, Pierre Buekens","doi":"10.1007/s40264-024-01458-w","DOIUrl":"10.1007/s40264-024-01458-w","url":null,"abstract":"<p><strong>Background: </strong>Pregnant persons are susceptible to significant complications following COVID-19, even death. However, worldwide COVID-19 vaccination coverage during pregnancy remains suboptimal.</p><p><strong>Objective: </strong>This study assessed the safety and effectiveness of COVID-19 vaccines administered to pregnant persons and shared this evidence via an interactive online website.</p><p><strong>Methods: </strong>We followed Cochrane methods to conduct this living systematic review. We included studies assessing the effects of COVID-19 vaccines in pregnant persons. We conducted searches every other week for studies until October 2023, without restrictions on language or publication status, in ten databases, guidelines, preprint servers, and COVID-19 websites. The reference lists of eligible studies were hand searched to identify additional relevant studies. Pairs of review authors independently selected eligible studies using the web-based software COVIDENCE. Data extraction and risk of bias assessment were performed independently by pairs of authors. Disagreements were resolved by consensus. We performed random-effects meta-analyses of adjusted relative effects for relevant confounders of comparative studies and proportional meta-analyses to summarize frequencies from one-sample studies using R statistical software. We present the GRADE certainty of evidence from comparative studies. Findings are available on an interactive living systematic review webpage, including an updated evidence map and real-time meta-analyses customizable by subgroups and filters.</p><p><strong>Results: </strong>We included 177 studies involving 638,791 participants from 41 countries. Among the 11 types of COVID-19 vaccines identified, the most frequently used platforms were mRNA (154 studies), viral vector (51), and inactivated virus vaccines (17). Low to very low-certainty evidence suggests that vaccination may result in minimal to no important differences compared to no vaccination in all assessed maternal and infant safety outcomes from 26 fewer to 17 more events per 1000 pregnant persons, and 13 fewer to 9 more events per 1000 neonates, respectively. We found statistically significant reductions in emergency cesarean deliveries (9%) with mRNA vaccines, and in stillbirth (75-83%) with mRNA/viral vector vaccines. Low to very low-certainty evidence suggests that vaccination during pregnancy with mRNA vaccines may reduce severe cases or hospitalizations in pregnant persons with COVID-19 (72%; 95% confidence interval [CI] 42-86), symptomatic COVID-19 (78%; 95% CI 21-94), and virologically confirmed SARS-CoV-2 infection (82%; 95% CI 39-95). Reductions were lower with other vaccine types and during Omicron variant dominance than Alpha and Delta dominance. Infants also presented with fewer severe cases or hospitalizations due to COVID-19 and laboratory-confirmed SARS-CoV-2 infection (64%; 95% CI 37-80 and 66%; 95% CI 37-81, respectively).</p><p><str","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11399161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What is the Safety of COVID-19 Vaccines in Immunocompromised Patients? Results from the European \"Covid Vaccine Monitor\" Active Surveillance Study.","authors":"Chiara Bellitto, Nicoletta Luxi, Francesco Ciccimarra, Luca L'Abbate, Monika Raethke, Florence van Hunsel, Thomas Lieber, Erik Mulder, Fabio Riefolo, Felipe Villalobos, Nicolas H Thurin, Francisco B Marques, Kathryn Morton, Fergal O'Shaughnessy, Simona Sonderlichová, Andreea Farcas, Giele-Eshuis Janneke, Miriam C Sturkenboom, Gianluca Trifirò","doi":"10.1007/s40264-024-01449-x","DOIUrl":"10.1007/s40264-024-01449-x","url":null,"abstract":"<p><strong>Background: </strong>The safety profile of COVID-19 vaccines in immunocompromised patients has not been comprehensively evaluated.</p><p><strong>Aim: </strong>To measure the frequency of patient-reported adverse drug reactions (ADRs) related to the first/second/booster dose of COVID-19 vaccine in immunocompromised subject versus matched cohort. As a secondary objective, the time course, evaluated as time to onset (TTO) and time to recovery (TTR), of COVID-19 vaccine-related ADRs was explored.</p><p><strong>Methods: </strong>A prospective cohort study, based on electronic questionnaires filled by vaccinees from 11 European countries in the period February 2021 to February 2023 was conducted. All immunocompromised vaccinees who provided informed consent and registered to the project's web-app within 48 h after first/booster vaccine dose administration of any EMA-authorised COVID-19 vaccine were recruited. Participants filled baseline and up to six follow-up questionnaires (FU-Qs) over 6 months from vaccination, collecting information on suspected COVID-19 vaccine-related ADRs. As a control group, non-immunocompromised vaccinees from the same source population were 1:4 matched by sex, age, vaccine dose, and brand. A descriptive analysis of demographic/clinical characteristics of vaccinees was conducted. Heatmaps of the frequency of solicited ADRs, stratified by gender and vaccine brand, were generated. Median TTO/TTR of reported ADRs were visualised using violin/box-plots.</p><p><strong>Results: </strong>A total of 773 immunocompromised vaccines were included in the analyses. Most participants were females (F/M ratio: 2.1 and 1.6) with a median age of 56 (43-74) and 51 (41-60) years, at the first vaccination cycle and booster dose, respectively. Injection-site pain and fatigue were the most frequently reported ADRs in immunocompromised vaccinees with higher frequency than matched control, especially after the first dose (41.2% vs 37.8% and 38.2% vs 32.9%, respectively). For both cohorts, all solicited ADRs were more frequently reported in females than males, and in those who had received a first dose of the Vaxzevria vaccine. Dizziness was the most frequently reported unsolicited ADR after the first dose in both groups (immunocompromised subjects: 2.5% and matched controls: 2.1%). At the booster dose, lymphadenopathy (3.9%) and lymphadenitis (1.8%) were the most reported unsolicited ADRs for immunocompromised subjects and matched controls, respectively. A very low number of subjects reported adverse event of special interest (AESI) (2 immunocompromised, 3 matched controls) and serious ADRs (5 immunocompromised, 5 matched controls). A statistically significant difference among study cohorts was observed for median TTO after the booster dose, and for median TTR after the first vaccination cycle and booster dose (p < 0.001).</p><p><strong>Conclusion: </strong>The overall safety profile of COVID-19 vaccines in immunocompromised people was fav","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11399172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141440296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pregnancy Outcomes in Patients Treated with Upadacitinib: Analysis of Data from Clinical Trials and Postmarketing Reports.","authors":"Uma Mahadevan, Gweneth Levy, Lianne Gensler, Mira Ali, Ana P Lacerda, Lani Wegrzyn, Hannah Palac, Tina Bhutani-Jacques, Millie Long, Megan E B Clowse, Alexa B Kimball, Christina Chambers, Anthony R Scialli","doi":"10.1007/s40264-024-01454-0","DOIUrl":"10.1007/s40264-024-01454-0","url":null,"abstract":"<p><strong>Background and objective: </strong>Upadacitinib is indicated for diseases affecting persons of childbearing potential including rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, atopic dermatitis, Crohn's disease, and ulcerative colitis; however, teratogenicity was observed in animal studies. Given the potential for human fetal risk, pregnancy avoidance measures were required during clinical trials. This analysis describes pregnancy outcomes in patients exposed to upadacitinib during pregnancy.</p><p><strong>Methods: </strong>Clinical trial and postmarketing cases of in utero exposure to upadacitinib were identified in AbbVie's safety database through 25 April, 2023. Analysis of clinical trial cases and postmarketing reports are presented separately; prospective and retrospectively reported pregnancy outcomes are integrated for each. Descriptive rates are presented to summarize outcomes.</p><p><strong>Results: </strong>There were 128 maternal upadacitinib-exposed pregnancies with known outcomes identified; 80 and 48 pregnancies were reported in clinical trials and the postmarketing setting, respectively. In clinical trials (mean in utero exposure of 5 weeks, 3 days), live births (54%), spontaneous abortions (24%), elective terminations (21%), and ectopic pregnancy (1%) were reported. There was one report of a congenital malformation: a 35-week infant with an atrial septal defect. In postmarketing cases, live births (46%), spontaneous abortions (38%), elective terminations (15%), and ectopic pregnancy (2%) were reported.</p><p><strong>Conclusions: </strong>As the data are limited for in utero exposure to upadacitinib, definitive conclusions cannot be drawn regarding the effect of upadacitinib on pregnancy outcomes. Rates of adverse pregnancy outcomes with upadacitinib exposure were comparable to rates observed in the general population or patients with autoimmune inflammatory diseases. To date, no apparent evidence of teratogenicity exists in the analyses of human pregnancies exposed to upadacitinib during the first trimester.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11399166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Effectiveness and Safety of Tixagevimab-Cilgavimab: A Target Trial Emulation Study.","authors":"Vincent Ka Chun Yan, Yu Yang, Eric Yuk Fai Wan, Francisco Tsz Tsun Lai, Celine Sze Ling Chui, Xue Li, Carlos King Ho Wong, Ivan Fan Ngai Hung, Chak Sing Lau, Ian Chi Kei Wong, Esther Wai Yin Chan","doi":"10.1007/s40264-024-01450-4","DOIUrl":"10.1007/s40264-024-01450-4","url":null,"abstract":"<p><strong>Background: </strong>Immunocompromised individuals are at high risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and subsequent severe or fatal coronavirus disease 2019 (COVID-19), yet they have suboptimal responses to mRNA and inactivated COVID-19 vaccines. The efficacy of tixagevimab-cilgavimab in reducing symptomatic SARS-CoV-2 infection was demonstrated in phase III clinical trials. Nevertheless, real-world data on the effectiveness and safety of tixagevimab-cilgavimab remain limited.</p><p><strong>Objective: </strong>The aim was to evaluate the effectiveness and safety of tixagevimab-cilgavimab among immunocompromised individuals.</p><p><strong>Methods: </strong>Adults who were immunocompromised or receiving immunosuppressive therapies were included in this target trial emulation using territory-wide electronic health records in Hong Kong. A sequential trial emulation approach was adopted to compare effectiveness and safety outcomes between individuals who received tixagevimab-cilgavimab and individuals who did not.</p><p><strong>Results: </strong>A total of 746 tixagevimab-cilgavimab recipients and 2980 controls were included from 1 May 2022 to 30 November 2022. Tixagevimab-cilgavimab significantly reduced the risk of COVID-19 infection (hazard ratio [HR] 0.708, 95% confidence interval [CI] 0.527-0.951) during a median follow-up of 60 days. No significant difference was observed in the risk of COVID-19-related hospitalisation. Zero versus eight COVID-19 mortality cases and zero versus two severe COVID-19 cases were observed in tixagevimab-cilgavimab recipients and controls, respectively. Notably, significant risk reduction in COVID-19 infection was also observed among immunocompromised individuals who had been previously vaccinated with three or more doses of COVID-19 vaccine, or had no prior COVID-19 infection history.</p><p><strong>Conclusions: </strong>Tixagevimab-cilgavimab was effective in reducing COVID-19 infection among immunocompromised patients during the Omicron wave. Findings were consistent among individuals who previously received three or more doses of COVID-19 vaccine, or had no previous history of COVID-19 infection.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11399184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141445885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The PrescIT platform: An interoperable Clinical Decision Support System for ePrescription to Prevent Adverse Drug Reactions and Drug-Drug Interactions.","authors":"Pantelis Natsiavas, George Nikolaidis, Jenny Pliatsika, Achilles Chytas, George Giannios, Haralampos Karanikas, Margarita Grammatikopoulou, Martha Zachariadou, Vlasios Dimitriadis, Spiros Nikolopoulos, Ioannis Kompatsiaris","doi":"10.1007/s40264-024-01455-z","DOIUrl":"10.1007/s40264-024-01455-z","url":null,"abstract":"<p><strong>Introduction: </strong>Preventable medication errors have been proven to cause significant public health burden, and ePrescription is a key part of the process where medication errors and adverse effects could be prevented. Information systems and \"intelligent\" computational approaches could provide a valuable tool to prevent such errors with profound impact in clinical practice.</p><p><strong>Objectives: </strong>The PrescIT platform is a Clinical Decision Support System (CDSS) that aims to facilitate the prevention of adverse drug reactions (ADRs) and drug-drug interactions (DDIs) in the phase of ePrescription in Greece. The proposed platform could be relatively easily localized for use in other contexts too.</p><p><strong>Methods: </strong>The PrescIT platform is based on the use of Knowledge Engineering (ΚΕ) approaches, i.e., the use of Ontologies and Knowledge Graphs (KGs) developed upon openly available data sources. Open standards (i.e., RDF, OWL, SPARQL) are used for the development of the platform enabling the integration with already existing IT systems or for standalone use. The main KG is based on the use of DrugBank, MedDRA, SemMedDB and OpenPVSignal. In addition, the Business Process Management Notation (BPMN) has been used to model long-term therapeutic protocols used during the ePrescription process. Finally, the produced software has been pilot tested in three hospitals by 18 clinical professionals via in-person think-aloud sessions.</p><p><strong>Results: </strong>The PrescIT platform has been successfully integrated in a transparent fashion in a proprietary Hospital Information System (HIS), and it has also been used as a standalone application. Furthermore, it has been successfully integrated with the Greek National ePrescription system. During the pilot phase, one psychiatric therapeutic protocol was used as a testbed to collect end-users' feedback. Summarizing the feedback from the end-users, they have generally acknowledged the usefulness of such a system while also identifying some challenges in terms of usability and the overall user experience.</p><p><strong>Conclusions: </strong>The PrescIT platform has been successfully deployed and piloted in real-world environments to evaluate its ability to support safer medication prescriptions.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The STAR Compass to Guide Future Pharmacovigilance Based on a 10-Year Review of the Strengthened EU System.","authors":"Priya Bahri, Georgy Genov, Peter Arlett, Viola Macolić Šarinić, Evdokia Korakianiti, Alexis Nolte, Martin Huber, Sabine M J M Straus","doi":"10.1007/s40264-024-01451-3","DOIUrl":"10.1007/s40264-024-01451-3","url":null,"abstract":"<p><p>This article reflects on the 2010 pharmacovigilance legislation of the European Union (EU). Its legislative aim of better patient and public health protection through new responsibilities for pharmaceutical companies and regulatory bodies is considered to have been achieved and is well supported by the good pharmacovigilance practices 'EU-GVP'. For future progress, we set out a vision for high-quality pharmacovigilance in a world of ongoing medical, technological and social changes. To deliver this vision, four principles are proposed to guide actions for further progressing the EU pharmacovigilance system: synergistic interactions with healthcare systems; trustworthy evidence for regulatory decisions; adaptive process efficiency; and readiness for emergency situations (the 'STAR principles'). Like a compass, these principles should guide actions for building capacity, technology and methods; improving regulatory processes; and expanding policies, frameworks and research agendas. Fit for the future, the EU system should achieve further improved outputs in terms of safe, effective and trusted use of medicines and positive health outcomes within patient-centred healthcare.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11399220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of the Role of Chemical Analysis in Causality Assessment of Herbal and Dietary Supplement-Induced Liver Injury.","authors":"Dina Halegoua-DeMarzio, Victor J Navarro, Ashley Davis, Jawad Ahmad, Bharathi Avula, Huiman Barnhart, A Sidney Barritt, Herbert L Bonkovsky, Vincent L Chen, Gina Choi, Robert J Fontana, Marwan S Ghabril, Ikhlas Khan, Christopher Koh, Joseph Odin, Don C Rockey, Hoss Rostami, Jose Serrano, Averell H Sherker, Andrew Stolz, Hans L Tillmann, Raj Vuppalanchi","doi":"10.1007/s40264-024-01484-8","DOIUrl":"https://doi.org/10.1007/s40264-024-01484-8","url":null,"abstract":"<p><strong>Background: </strong> The attribution of drug-induced liver injury (DILI) to specific herbal and dietary supplements (HDS) is confounded by inaccurate labels and undisclosed ingredients. The US Drug-Induced Liver Injury Network (DILIN) determines the attribution of injury to an agent through its structured expert opinion causality assessment process, but without the use of chemical analysis data of HDS. We aimed to determine the impact of chemical analysis of HDS products on prior causality assessment scores.</p><p><strong>Methods: </strong>Obtained samples of HDS consumed by DILIN-enrolled patients were analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS). Chemical analysis data were compared to label accuracy and detect whether the product contained botanical and non-botanical compounds. A comparison of the causality scores reassessed with chemical analysis was compared with the original scores.</p><p><strong>Results: </strong>A total of 54 previously adjudicated cases with chemical analysis available were reassessed for causality with chemical analysis data; reviewers were blinded to original causality scores. Using the chemical analysis data, 37% (n = 20) of the 54 cases were scored with a higher likelihood of DILI compared with the original causality scores; 14 of the 20 (70%) moved from probable to highly likely; 52% had no change in causality score; and 11% of cases were scored as a lower likelihood of DILI.</p><p><strong>Conclusions: </strong> Our study demonstrates that there is value in using HDS chemical analysis data in the causality assessment process for DILI. In more than a third of cases, chemical analysis of products led to an increased confidence in DILI attribution to HDS. These findings suggest that chemical analysis is an important tool in causality assessment for HDS agents, specifically in challenging situations, and further studies are needed to confirm its applicability in clinical practice.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safeguarding Patients in the AI Era: Ethics at the Forefront of Pharmacovigilance.","authors":"Ashish Jain, Maribel Salas, Omar Aimer, Zahabia Adenwala","doi":"10.1007/s40264-024-01483-9","DOIUrl":"https://doi.org/10.1007/s40264-024-01483-9","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Integrated Approach for Representing Knowledge on the Potential of Drugs to Cause Acute Kidney Injury.","authors":"Daniel Fernández-Llaneza, Romy M P Vos, Joris E Lieverse, Helen R Gosselt, Sandra L Kane-Gill, Teun van Gelder, Joanna E Klopotowska","doi":"10.1007/s40264-024-01474-w","DOIUrl":"https://doi.org/10.1007/s40264-024-01474-w","url":null,"abstract":"<p><strong>Introduction and objective: </strong>The recent rise in acute kidney injury (AKI) incidence, with approximately 30% attributed to potentially preventable adverse drug events (ADEs), poses challenges in evaluating drug-induced AKI due to polypharmacy and other risk factors. This study seeks to consolidate knowledge on the drugs with AKI potential from four distinct sources: (i) bio(medical) peer-reviewed journals; (ii) spontaneous reporting systems (SRS); (iii) drug information databases (DIDs); and (iv) NephroTox website. By harnessing the potential of these underutilised sources, our objective is to bridge gaps and enhance the understanding of drug-induced AKI.</p><p><strong>Methods: </strong>By searching Medline, studies with lists of drugs with AKI potential established through consensus amongst medical experts were selected. A final list of 63 drugs was generated aggregating the original studies. For these 63 drugs, the AKI reporting odds ratios (RORs) using three SRS databases, the average frequency of ADEs from four different DIDs and the number of published studies identified via NephroTox was reported.</p><p><strong>Results: </strong>Drugs belonging to the antivirals, antibacterials, and non-steroidal anti-inflammatory pharmacological classes exhibit substantial consensus on AKI potential, which was also reflected in strong ROR signals, frequent to very frequent AKI-related ADEs and a high number of published studies reporting adverse kidney events as identified via NephroTox. Renin-angiotensin aldosterone system inhibitors and diuretics also display comparable signal strengths, but this can be attributed to expected haemodynamic changes. More variability is noted for proton-pump inhibitors.</p><p><strong>Conclusions: </strong>By integrating four disjointed sources of knowledge, we have created a novel, comprehensive resource on drugs with AKI potential, contributing to kidney safety improvement efforts.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}