{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T01:53:02Z","timestamp":1775094782209,"version":"3.50.1"},"reference-count":7,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ther Innov Regul Sci"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>European legislation requires Marketing Authorization Holders (MAHs) to continuously monitor Eudravigilance (EV) data and inform the European Medicines Agency and national competent authorities of validated safety signals. The process follows the Good Pharmacovigilance Practice Module IX and is based on the review of individual case safety reports (ICSR) both from the MAH\u2019s internal database and from EV. The data is reviewed and evaluated by a medically trained person, who should, based on the information provided in the case, determine the causal relationship between the suspect drug and the reported event. In order to do this with a certain degree of confidence, the case needs to report enough high-quality information on the drug, patient and adverse event, without significant confounders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>For this purpose, we performed an evaluation of data quality of ICSRs within the Eudravigilance database, focusing on drug toxicity cases for five commonly implicated substances: paracetamol, diazepam, fentanyl, quetiapine, and fluoxetine. A medically driven review was conducted on 500 randomly selected ICSRs from 2015 to 2024. A detailed quality assessment framework was developed and applied, scoring cases across several criteria (including data on suspect drugs, patient demographics, adverse event description, time to event, and case narratives), resulting in a maximum quality score of 25.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Main study findings revealed a generally low data quality, with an average score of 11.57 out of 25. Key quality deficiencies included improper classification of drugs as suspects (e.g., reporting concomitant medications or treatments as suspects), reporting of underlying diseases and indications as adverse events, lack of information on patients\u2019 medical history and missing time-to-event information. Cases from non-European Economic Area (non-EEA) countries and consumer-reported cases exhibited the lowest quality, while regulatory agency-reported cases were of higher quality. The study also identified a frequent misclassification of non-prescription or illicit substances (e.g., fentanyl) as prescription products, complicating signal detection and causality assessments. The analysis highlights a very important gap in pharmacovigilance signal detection and evaluation processes, underscoring risks for misleading results, increased workload, and potential misinterpretation of product safety profiles. The results highlight the need for enhanced case reporting trainings, improved quality control, better follow-up processes, and a collective mindset shift across stakeholders to prioritize data quality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In conclusion, significant improvements in the completeness, accuracy, and clinical relevance of ICSRs are essential to support effective safety signal detection and benefit-risk assessment in the post-marketing surveillance of medicinal products.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s43441-025-00884-x","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T19:34:27Z","timestamp":1760643267000},"page":"285-292","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Quality of Reports on Drug Toxicity in Eudravigilance: A Safety Physician\u2019s Perspective"],"prefix":"10.1007","volume":"60","author":[{"given":"Jana Brajdih","family":"\u010cendak","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"key":"884_CR1","unstructured":"Commission Implementing Regulation (EU) 2025\/1466 of 22 July 2025 amending Implementing Regulation (EU) No 520\/2012 on the performance of pharmacovigilance activities provided for in Regulation (EC) No 726\/2004 and Directive 2001\/83\/EC. Official Journal of the European Union. L series. July 23, 2025. Accessed August 26, 2025. https:\/\/eur-lex.europa.eu\/eli\/reg_impl\/2025\/1466\/oj\/eng"},{"key":"884_CR2","unstructured":"European Medicines Agency. Guideline on Good Pharmacovigilance Practices (GVP): Module IX\u2014Signal Management. EMA. 2012 (rev. March 2017). Accessed August 26, 2025. https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/guideline-good-pharmacovigilance-practices-gvp-module-ix-signal-management_en.pdf"},{"issue":"10","key":"884_CR3","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1080\/15563650.2021.1884693","volume":"59","author":"\u00d2 Mir\u00f3","year":"2021","unstructured":"Mir\u00f3 \u00d2, Waring WS, Dargan PI, Wood DM, Dines AM, Yates C, Giraudon I, Moughty A, O\u2019Connor N, Heyerdahl F, Hovda KE, Vallersnes OM, Paasma R, Pold K, J\u00fcrgens G, Megarbane B, Anand JS, Liakoni E, Liechti M, Eyer F, Zacharov S, Caganova B, Bonnici J, Radenkova-Saeva J, Galicia M, Euro-DEN Plus Research Group. Variation of drugs involved in acute drug toxicity presentations based on age and sex: an epidemiological approach based on European emergency departments. Clin Toxicol (Phila). 2021;59(10):896\u2013904.","journal-title":"Clin Toxicol (Phila)"},{"issue":"2","key":"884_CR4","doi-asserted-by":"publisher","first-page":"308","DOI":"10.3390\/ph16020308","volume":"16","author":"T Nascimento","year":"2023","unstructured":"Nascimento T, Santos T, Rato F, De Sousa-Coelho AL. Characterization of potential intoxications with medicines in a regional setting. Pharmaceuticals. 2023;16(2):308. https:\/\/doi.org\/10.3390\/ph16020308.","journal-title":"Pharmaceuticals"},{"key":"884_CR5","unstructured":"Khalid MM, Waseem M. Tricyclic Antidepressant Toxicity. [Updated 2023 Jul 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 January. Available from: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK430931\/"},{"key":"884_CR6","unstructured":"ANSES toxicovigilance report on accidental toxic exposure in children\u2014study of data from several sources of recourse to care between 2014 and 2020. Anses (Agencie nationale de securite sanitaire) April 2024. Accessed 07.04.2025. Available from: https:\/\/vigilanses.anses.fr\/sites\/default\/files\/VigilAnses_N22_Accidentalpoisoningchildren.pdf"},{"key":"884_CR7","unstructured":"Council of the European Union. Opioids: a new drug threat for Europe. Updated July 29, 2025. Accessed August 26. 2025. https:\/\/www.consilium.europa.eu\/en\/policies\/opioids-drugs-heroin\/"}],"container-title":["Therapeutic Innovation &amp; Regulatory Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43441-025-00884-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s43441-025-00884-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43441-025-00884-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T03:02:11Z","timestamp":1767150131000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s43441-025-00884-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,16]]},"references-count":7,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["884"],"URL":"https:\/\/doi.org\/10.1007\/s43441-025-00884-x","relation":{},"ISSN":["2168-4790","2168-4804"],"issn-type":[{"value":"2168-4790","type":"print"},{"value":"2168-4804","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,16]]},"assertion":[{"value":"12 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}]}}