{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T06:08:16Z","timestamp":1788761296607,"version":"build-2803163510"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Pediatric adverse drug reactions are difficult to evaluate after approval because pediatric trial evidence is limited and spontaneous-report systems differ in product naming, event coding, seriousness fields, and duplicate submissions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We developed a manufacturer-aware benchmark for pediatric pharmacovigilance signal concordance using the FDA Adverse Event Reporting System (FAERS)\/AERS as the source system, Canada Vigilance as a cross-system reporting-signal comparator, and JADER for descriptive third-country context. Active ingredients and five clinically adjudicated serious endpoint families were harmonized before detectable manufacturer cross-filing was screened.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The supervised benchmark contained 628 drug\u2013endpoint\u2013period rows: 147 manufacturer-screened Canada Vigilance reporting-signal positives and 481 Canada Vigilance co-report-absent comparators. An endpoint-conditioned FAERS co-reporting comparator achieved an area under the precision\u2013recall curve (AUPRC) of 0.753. Elastic-net logistic regression reached 0.767, and a LightGBM comparator reached 0.774, but clustered paired-difference intervals\n                      <jats:italic>versus<\/jats:italic>\n                      the conditioned co-report comparator included zero. In 30 repeated drug-held-out partitions, chemical structure increased the mean AUPRC from 0.764 to 0.796, but the corresponding increment was \u20130.003 under unseen-scaffold partitions; target and pathway indicators produced no further material increase. Future-period support was concentrated in anaphylaxis: 40 drug pairs remained after manufacturer screening, including 37 with FAERS source exposure, and four of five FAERS scores ranked supported pairs above permutation expectations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Clinical label specificity, detectable duplicate screening, and fair source-signal comparators materially influenced model evaluation. The resulting resource provides a reproducible reference for pediatric signal triage and for testing whether new pharmacological features or models add information beyond established reporting statistics.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1900271","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T05:33:51Z","timestamp":1788759231000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A manufacturer-aware cross-system benchmark for pediatric pharmacovigilance signal concordance"],"prefix":"10.3389","volume":"17","author":[{"given":"Jinwan","family":"Shi","sequence":"first","affiliation":[{"name":"Foshan Sanshui District People\u2019s Hospital","place":["Foshan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieting","family":"Xia","sequence":"additional","affiliation":[{"name":"Foshan Sanshui District People\u2019s Hospital","place":["Foshan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanqiong","family":"Li","sequence":"additional","affiliation":[{"name":"Foshan Sanshui District People\u2019s Hospital","place":["Foshan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Medical Information Engineering, Guangdong Pharmaceutical University","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowen","family":"Shi","sequence":"additional","affiliation":[{"name":"School of Medical Information Engineering, Guangdong Pharmaceutical University","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2042098620938595","DOI":"10.1177\/2042098620938595","article-title":"Post marketing surveillance of suspected adverse drug reactions through spontaneous reporting: current status, challenges and the future","volume":"11","author":"Alomar","year":"2020","journal-title":"Ther. Adv. Drug Saf."},{"key":"B2","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1111\/bcp.12944","article-title":"Adverse drug event reporting systems: a systematic review","volume":"82","author":"Bailey","year":"2016","journal-title":"Br. J. Clin. Pharmacol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1007\/s002280050466","article-title":"A Bayesian neural network method for adverse drug reaction signal generation","volume":"54","author":"Bate","year":"1998","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"e1001885","DOI":"10.1371\/journal.pmed.1001885","article-title":"The reporting of studies conducted using observational routinely-collected health data (RECORD) statement","volume":"12","author":"Benchimol","year":"2015","journal-title":"PLoS Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1804","DOI":"10.1111\/epi.18338","article-title":"Updated classification of epileptic seizures: position paper of the international league against epilepsy","volume":"66","author":"Beniczky","year":"2025","journal-title":"Epilepsia"},{"key":"B6","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1111\/bcp.12645","article-title":"Pharmacovigilance in children: detecting adverse drug reactions in routine electronic healthcare records. a systematic review","volume":"80","author":"Black","year":"2015","journal-title":"Br. J. Clin. Pharmacol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"100472","DOI":"10.1016\/j.waojou.2020.100472","article-title":"World Allergy Organization anaphylaxis guidance 2020","volume":"13","author":"Cardona","year":"2020","journal-title":"World Allergy Organ. J."},{"key":"B8","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1002\/pds.4970","article-title":"Adverse drug reaction or innocent bystander? A systematic comparison of statistical discovery methods for spontaneous reporting systems","volume":"29","author":"Dijkstra","year":"2020","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"B9","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1186\/s13690-024-01295-4","article-title":"The epidemiology of drug-related hospital admissions in paediatrics: a systematic review","volume":"82","author":"Eberl","year":"2024","journal-title":"Archives Public Health"},{"key":"B10","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1002\/pds.677","article-title":"Use of proportional reporting ratios (PRRs) for signal generation from spontaneous adverse drug reaction reports","volume":"10","author":"Evans","year":"2001","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"B11","doi-asserted-by":"publisher","first-page":"23636","DOI":"10.1038\/s41598-024-74505-2","article-title":"Prediction of adverse drug reactions using demographic and non-clinical drug characteristics in FAERS data","volume":"14","author":"Farnoush","year":"2024","journal-title":"Sci. Rep."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1002\/hep.32689","article-title":"AASLD practice guidance on drug, herbal, and dietary supplement-induced liver injury","volume":"77","author":"Fontana","year":"2023","journal-title":"Hepatology"},{"key":"B13","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1007\/s40264-024-01421-9","article-title":"The reporting of a disproportionality analysis for drug safety signal detection using individual case safety reports in pharmacovigilance (READUS-PV): development and statement","volume":"47","author":"Fusaroli","year":"","journal-title":"Drug Saf."},{"key":"B14","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1007\/s40264-024-01423-7","article-title":"The reporting of a disproportionality analysis for drug safety signal detection using individual case safety reports in pharmacovigilance (READUS-PV): explanation and elaboration","volume":"47","author":"Fusaroli","year":"","journal-title":"Drug Saf."},{"key":"B15","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1016\/j.medj.2022.06.001","article-title":"A database of pediatric drug effects to evaluate ontogenic mechanisms from child growth and development","volume":"3","author":"Giangreco","year":"2022","journal-title":"Med"},{"key":"B16","doi-asserted-by":"publisher","first-page":"D687","DOI":"10.1093\/nar\/gkab1028","article-title":"The Reactome pathway knowledgebase 2022","volume":"50","author":"Gillespie","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"B17","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1007\/s40264-023-01345-w","article-title":"Challenges and opportunities in accessing and analysing FAERS data: a call towards a collaborative approach","volume":"46","author":"Giunchi","year":"2023","journal-title":"Drug Saf."},{"key":"B18","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1016\/j.clinthera.2024.06.003","article-title":"Knowledge graphs in pharmacovigilance: a scoping review","volume":"46","author":"Hauben","year":"2024","journal-title":"Clin. Ther."},{"key":"B19","volume-title":"Canada Vigilance Adverse Reaction Online Database","year":"2026"},{"key":"B20","doi-asserted-by":"publisher","first-page":"e5768","DOI":"10.1002\/pds.5768","article-title":"Adverse drug reaction signal detection methods in spontaneous reporting system: a systematic review","volume":"33","author":"Jiao","year":"2024","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"B21","first-page":"3146","article-title":"LightGBM: a highly efficient gradient boosting decision tree","volume":"30","author":"Ke","year":"2017","journal-title":"Adv. Neural Inf. Process. Syst."},{"key":"B22","doi-asserted-by":"publisher","first-page":"2417399","DOI":"10.1080\/20523211.2024.2417399","article-title":"Pharmacovigilance: the evolution of drug safety monitoring","volume":"17","author":"Khan","year":"2024","journal-title":"J. Pharm. Policy Pract."},{"key":"B23","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1136\/postgradmedj-2020-138661","article-title":"Managing drug-induced QT prolongation in clinical practice","volume":"97","author":"Khatib","year":"2021","journal-title":"Postgrad. Med. J."},{"key":"B24","first-page":"1","article-title":"KDIGO clinical practice guideline for acute kidney injury","volume":"2","year":"2012","journal-title":"Kidney Int. Suppl."},{"key":"B25","doi-asserted-by":"publisher","first-page":"e081990","DOI":"10.1136\/bmjopen-2023-081990","article-title":"Navigating duplication in pharmacovigilance databases: a scoping review","volume":"14","author":"Kiguba","year":"2024","journal-title":"BMJ Open"},{"key":"B26","year":"2026"},{"key":"B27","doi-asserted-by":"publisher","first-page":"D930","DOI":"10.1093\/nar\/gky1075","article-title":"ChEMBL: towards direct deposition of bioassay data","volume":"47","author":"Mendez","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1136\/amiajnl-2011-000116","article-title":"Normalized names for clinical drugs: RxNorm at 6 years","volume":"18","author":"Nelson","year":"2011","journal-title":"J. Am. Med. Inf. Assoc."},{"key":"B29","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1007\/s40264-015-0265-0","article-title":"Pediatric drug safety signal detection: a new drug-event reference set for performance testing of data-mining methods and systems","volume":"38","author":"Osokogu","year":"2015","journal-title":"Drug Saf."},{"key":"B30","doi-asserted-by":"publisher","first-page":"e70216","DOI":"10.1002\/pds.70216","article-title":"Aioli: standardising drugs in the FDA adverse event reporting system (FAERS) to RxNorm and anatomical therapeutic chemical (ATC) codes","volume":"34","author":"Parry","year":"2025","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"B31","first-page":"2825","article-title":"Scikit-learn: Machine Learning in Python","volume":"12","author":"Pedregosa","year":"2011","journal-title":"J. Mach. Learn. Res."},{"key":"B32","volume-title":"Japanese Adverse Drug Event Report Database","year":"2026"},{"key":"B33","doi-asserted-by":"publisher","first-page":"2092","DOI":"10.1111\/bcp.16153","article-title":"Moderate and serious adverse reactions to antimicrobials among hospitalized children: a systematic review","volume":"90","author":"Ramos","year":"2024","journal-title":"Br. J. Clin. Pharmacol."},{"key":"B34","year":"2026"},{"key":"B35","doi-asserted-by":"publisher","first-page":"742","DOI":"10.1021\/ci100050t","article-title":"Extended-connectivity fingerprints","volume":"50","author":"Rogers","year":"2010","journal-title":"J. Chem. Inf. Model."},{"key":"B36","doi-asserted-by":"publisher","first-page":"40","DOI":"10.23876\/j.krcp.20.074","article-title":"Pediatric acute kidney injury: new advances in the last decade","volume":"40","author":"Sethi","year":"2021","journal-title":"Kidney Res. Clin. Pract."},{"key":"B37","doi-asserted-by":"publisher","first-page":"e24061","DOI":"10.1371\/journal.pone.0024061","article-title":"Adverse drug reactions in children: a systematic review","volume":"7","author":"Smyth","year":"2012","journal-title":"PLoS One"},{"key":"B38","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/s42004-025-01865-9","article-title":"Machine learning prediction of pediatric adverse drug reactions using consensus-derived scarce data","volume":"9","author":"Tian","year":"2026","journal-title":"Commun. Chem."},{"key":"B39","doi-asserted-by":"publisher","first-page":"D932","DOI":"10.1093\/nar\/gkw993","article-title":"DrugCentral: online drug compendium","volume":"45","author":"Ursu","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"B40","volume-title":"E14 and S7B Clinical and Nonclinical Evaluation of QT\/QTc Interval Prolongation and Proarrhythmic Potential: Questions and Answers","year":"2022"},{"key":"B41","volume-title":"FDA Adverse Event Reporting System (FAERS) Public Dashboard and Quarterly Data Files","year":"2026"},{"key":"B42","volume-title":"RxNorm","year":"2026"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1002\/cpt.2736","article-title":"Off-label, but on-evidence? A review of the level of evidence for pediatric pharmacotherapy","volume":"112","author":"van der Zanden","year":"2022","journal-title":"Clin. Pharmacol. Ther"},{"key":"B44","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1002\/pds.668","article-title":"A comparison of measures of disproportionality for signal detection in spontaneous reporting systems for adverse drug reactions","volume":"11","author":"van Puijenbroek","year":"2002","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"B45","doi-asserted-by":"publisher","first-page":"e296","DOI":"10.1371\/journal.pmed.0040296","article-title":"The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies","volume":"4","author":"von Elm","year":"2007","journal-title":"PLoS Med."},{"key":"B46","volume-title":"Anatomical Therapeutic Chemical (ATC) Classification System","year":"2026"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1900271\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T05:33:53Z","timestamp":1788759233000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1900271\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,7]]},"references-count":46,"alternative-id":["10.3389\/fphar.2026.1900271"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1900271","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,7]]},"article-number":"1900271"}}