{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T19:57:29Z","timestamp":1781639849967,"version":"3.54.5"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":38,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Wilson\u2019s disease is a rare autosomal copper metabolism recessive disorder that requires lifelong pharmacological treatment. D-penicillamine and trientine are the most commonly used copper chelators. However, their post-marketing safety reporting patterns remain insufficiently characterized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a pharmacovigilance study using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and the World Health Organization\u2019s VigiAccess database. Because FAERS allows case-level signal detection whereas VigiAccess provides only aggregated data, analyses were intentionally restricted to parallel signal characterization, precluding event-matched or head-to-head comparisons. To reduce indication bias and ensure disease-specific assessment, FAERS analyses were restricted to reports explicitly listing \u201chepato-lenticular degeneration\u201d as the indication for use. Temporal, geographical, and demographic trends were evaluated, and disproportionality analyses\u2014including the reporting odds ratio (ROR), proportional reporting ratio (PRR), information component (IC), and multi-item gamma-Poisson shrinker (MGPS)\u2014were performed to identify and validate adverse drug event (ADE) signals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 641 cases were retrieved from FAERS and 4,560 from VigiAccess. Trientine accounted for most cases in FAERS, whereas D-penicillamine predominated in VigiAccess. Temporal analysis showed earlier reporting peaks for D-penicillamine in VigiAccess, while trientine displayed a progressive rise after 2000. Regional differences were evident, with Europe dominating VigiAccess reports and Asia\/America contributing more strongly to FAERS. Disproportionality analyses revealed significant signals: trientine was associated with hepatic failure, abdominal pain, tremor, nausea, and fatigue, while D-penicillamine demonstrated signals for dystonia, arthritis, tremor, and nausea. Extremely high estimates for hepato-lenticular degeneration likely reflect confounding by indication.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings characterize drug-specific safety reporting patterns for copper chelators used in Wilson\u2019s disease within two complementary pharmacovigilance systems. Rather than establishing relative safety, the observed differences reflect distinct reporting profiles shaped by database structure, regulatory context, and clinical use. Integrating national and international pharmacovigilance data provides complementary insights into post-marketing safety signals and may support tailored clinical monitoring strategies without implying head-to-head comparative risk.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13023-026-04310-9","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T17:03:38Z","timestamp":1773075818000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Post-marketing safety signals of Wilson\u2019s disease therapies: evidence from FAERS and VigiBase"],"prefix":"10.1186","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1843-3424","authenticated-orcid":false,"given":"H\u00fclya","family":"Tezel-Yal\u00e7\u0131n","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2280-8727","authenticated-orcid":false,"given":"Nadir","family":"Yal\u00e7\u0131n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9921-5105","authenticated-orcid":false,"given":"Karel","family":"Allegaert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4713-7672","authenticated-orcid":false,"given":"P\u0131nar","family":"Erkeko\u011flu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,9]]},"reference":[{"issue":"1","key":"4310_CR1","first-page":"e0238","volume":"23","author":"JS Dooley","year":"2024","unstructured":"Dooley JS. The history of Wilson disease. Clin Liver Dis (Hoboken). 2024;23(1):e0238.","journal-title":"Clin Liver Dis (Hoboken)"},{"key":"4310_CR2","unstructured":"European Association for the study of the liver. EASL-ERN clinical practice guidelines on wilson\u2019s disease. J Hepatol. 2025."},{"issue":"1","key":"4310_CR3","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1016\/j.jhep.2019.02.002","volume":"71","author":"P Ferenci","year":"2019","unstructured":"Ferenci P, Ott P. Wilson\u2019s disease: Fatal when overlooked, curable when diagnosed. J Hepatol. 2019;71(1):222\u20134.","journal-title":"J Hepatol"},{"issue":"2","key":"4310_CR4","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1016\/j.jceh.2021.05.013","volume":"12","author":"O Unavane","year":"2022","unstructured":"Unavane O, Tiwari K, Nagral A, Aggarwal R, Garg N, Nagral N, Verma B, Jhaveri A, Setia MS. Quality of Life of Patients with Wilson\u2019s Disease and Their Families. J Clin Exp Hepatol. 2022;12(2):461\u20136.","journal-title":"J Clin Exp Hepatol"},{"issue":"1","key":"4310_CR5","doi-asserted-by":"publisher","first-page":"8636","DOI":"10.1038\/s41598-024-59377-w","volume":"14","author":"T Zhan","year":"2024","unstructured":"Zhan T, Guan Y, Sun C, Wang L, Wang Y, Li X. Assessment and factors affecting quality of life among patients with Wilson\u2019s disease. Sci Rep. 2024;14(1):8636.","journal-title":"Sci Rep"},{"issue":"3","key":"4310_CR6","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.iliver.2022.09.002","volume":"1","author":"ZW Zheng","year":"2022","unstructured":"Zheng ZW, Dong Y, Wu ZY. Latest innovations in the treatment of Wilson\u2019s disease. ILIVER. 2022;1(3):181\u20136.","journal-title":"ILIVER"},{"key":"4310_CR7","unstructured":"Mejias SG, Patel P, Ramphul K. Penicillamine. edn. Treasure Island (FL); 2025. StatPearls."},{"key":"4310_CR8","unstructured":"Trientine. In: LiverTox: clinical and research information on drug-induced liver injury [ https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK548119\/]."},{"key":"4310_CR9","doi-asserted-by":"publisher","first-page":"847436","DOI":"10.3389\/fphar.2022.847436","volume":"13","author":"S Tang","year":"2022","unstructured":"Tang S, Bai L, Hou W, Hu Z, Chen X, Zhao J, Liang C, Zhang W, Duan Z, Zheng S. Comparison of the Effectiveness and Safety of d-Penicillamine and Zinc Salt Treatment for Symptomatic Wilson Disease: A Systematic Review and Meta-Analysis. Front Pharmacol. 2022;13:847436.","journal-title":"Front Pharmacol"},{"issue":"1","key":"4310_CR10","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1186\/s13023-024-03113-0","volume":"19","author":"MA Goktas","year":"2024","unstructured":"Goktas MA, Yalcin N. Adherence to medical treatment for Wilson\u2019s disease in children and adolescents: a cohort study from Turkey. Orphanet J Rare Dis. 2024;19(1):105.","journal-title":"Orphanet J Rare Dis"},{"issue":"6","key":"4310_CR11","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1016\/j.therap.2020.02.022","volume":"75","author":"K Bihan","year":"2020","unstructured":"Bihan K, Lebrun-Vignes B, Funck-Brentano C, Salem JE. Uses of pharmacovigilance databases: An overview. Therapie. 2020;75(6):591\u20138.","journal-title":"Therapie"},{"issue":"4","key":"4310_CR12","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1007\/s40264-019-00899-y","volume":"43","author":"U Vogel","year":"2020","unstructured":"Vogel U, van Stekelenborg J, Dreyfus B, Garg A, Habib M, Hosain R, Wisniewski A. Investigating Overlap in Signals from EVDAS, FAERS, and VigiBase((R)). Drug Saf. 2020;43(4):351\u201362.","journal-title":"Drug Saf"},{"issue":"5","key":"4310_CR13","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.1002\/cpt.2172","volume":"109","author":"A Lavertu","year":"2021","unstructured":"Lavertu A, Vora B, Giacomini KM, Altman R, Rensi S. A New Era in Pharmacovigilance: Toward Real-World Data and Digital Monitoring. Clin Pharmacol Ther. 2021;109(5):1197\u2013202.","journal-title":"Clin Pharmacol Ther"},{"issue":"25","key":"4310_CR14","doi-asserted-by":"publisher","first-page":"e29387","DOI":"10.1097\/MD.0000000000029387","volume":"101","author":"HR Kim","year":"2022","unstructured":"Kim HR, Sung M, Park JA, Jeong K, Kim HH, Lee S, Park YR. Analyzing adverse drug reaction using statistical and machine learning methods: A systematic review. Med (Baltim). 2022;101(25):e29387.","journal-title":"Med (Baltim)"},{"issue":"9559","key":"4310_CR15","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/S0140-6736(07)60196-2","volume":"369","author":"A Ala","year":"2007","unstructured":"Ala A, Walker AP, Ashkan K, Dooley JS, Schilsky ML. Wilson\u2019s disease. Lancet. 2007;369(9559):397\u2013408.","journal-title":"Lancet"},{"issue":"2","key":"4310_CR16","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1002\/jimd.12046","volume":"42","author":"J Pfeiffenberger","year":"2019","unstructured":"Pfeiffenberger J, Lohse CM, Gotthardt D, Rupp C, Weiler M, Teufel U, Weiss KH, Gauss A. Long-term evaluation of urinary copper excretion and non-caeruloplasmin associated copper in Wilson disease patients under medical treatment. J Inherit Metab Dis. 2019;42(2):371\u201380.","journal-title":"J Inherit Metab Dis"},{"issue":"11","key":"4310_CR17","doi-asserted-by":"publisher","first-page":"1443","DOI":"10.1080\/14740338.2021.1956460","volume":"20","author":"V Kumar","year":"2021","unstructured":"Kumar V, Singh AP, Wheeler N, Galindo CL, Kim JJ. Safety profile of D-penicillamine: a comprehensive pharmacovigilance analysis by FDA adverse event reporting system. Expert Opin Drug Saf. 2021;20(11):1443\u201350.","journal-title":"Expert Opin Drug Saf"},{"issue":"11","key":"4310_CR18","doi-asserted-by":"publisher","first-page":"e0336721","DOI":"10.1371\/journal.pone.0336721","volume":"20","author":"W Qian","year":"2025","unstructured":"Qian W, Xu K, Li S, Zhang Z, Hou X, Min B, Ling J, Zhu X, Zhou H, Xu W, et al. Safety of penicillamine and trientine in the treatment of Wilson\u2019s disease: An analysis of the FDA Adverse Event Reporting System (FAERS) database. PLoS ONE. 2025;20(11):e0336721.","journal-title":"PLoS ONE"},{"key":"4310_CR19","doi-asserted-by":"crossref","unstructured":"Akbulut S, Is S, Koprulu TK, Varol FI, Kucukakcali Z, Colak C, Koc A, Tekin S, Yilmaz S. Evaluation of the relationship between neurologic manifestations and genetic mutations in Wilson\u2019s Disease with next-generation sequencing. Diagnostics (Basel) 2025, 15(21).","DOI":"10.3390\/diagnostics15212689"},{"issue":"1","key":"4310_CR20","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1186\/s13023-025-03874-2","volume":"20","author":"L Zhang","year":"2025","unstructured":"Zhang L, Peng J, Dong Y, Zhang Q, Long W, Wang Y, Li Z, Long L, Li Y, Jin Q, et al. Assessment of neurological symptoms and associated factors in patients with Wilson\u2019s disease in Southwest China. Orphanet J Rare Dis. 2025;20(1):342.","journal-title":"Orphanet J Rare Dis"},{"key":"4310_CR21","doi-asserted-by":"crossref","unstructured":"Garbuz M, Ovchinnikova E, Ovchinnikova A, Vinokurova V, Aristarkhova Y, Kuziakova O, Mashurova M, Kumeiko V. Spectrum of pathogenic variants of the ATP7B gene and genotype-phenotype correlation in eastern eurasian patient cohorts with Wilson\u2019s disease. Biomedicines 2024, 12(12).","DOI":"10.3390\/biomedicines12122833"},{"issue":"11","key":"4310_CR22","doi-asserted-by":"publisher","first-page":"e109727","DOI":"10.1371\/journal.pone.0109727","volume":"9","author":"J Usta","year":"2014","unstructured":"Usta J, Wehbeh A, Rida K, El-Rifai O, Estiphan TA, Majarian T, Barada K. Phenotype-genotype correlation in Wilson disease in a large Lebanese family: association of c.2299insC with hepatic and of p. Ala1003Thr with neurologic phenotype. PLoS ONE. 2014;9(11):e109727.","journal-title":"PLoS ONE"},{"issue":"2","key":"4310_CR23","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1016\/j.dld.2024.09.002","volume":"57","author":"P Alonso-Castellano","year":"2025","unstructured":"Alonso-Castellano P, Tugores A, Marino Z, Olveira A, Berenguer M, Huarte MP, Fernandez-Ramos JR, Lazaro-Rios M, Gonzalez-Dieguez ML, Moreno-Planas JM, et al. Low penetrance of frequent ATP7B mutations explains the low prevalence of Wilson disease. Lessons from real-life registries. Dig Liver Dis. 2025;57(2):443\u20139.","journal-title":"Dig Liver Dis"},{"issue":"5","key":"4310_CR24","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1002\/ccr3.2125","volume":"7","author":"SK Pitman","year":"2019","unstructured":"Pitman SK, Huynh T, Bjarnason TA, An J, Malkhasyan KA. A case report and focused literature review of d-penicillamine and severe neutropenia: A serious toxicity from a seldom-used drug. Clin Case Rep. 2019;7(5):990\u20134.","journal-title":"Clin Case Rep"},{"issue":"8","key":"4310_CR25","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1002\/mds.10458","volume":"18","author":"JM Walshe","year":"2003","unstructured":"Walshe JM. The story of penicillamine: a difficult birth. Mov Disord. 2003;18(8):853\u20139.","journal-title":"Mov Disord"},{"issue":"12","key":"4310_CR26","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.1016\/S2468-1253(22)00270-9","volume":"7","author":"ML Schilsky","year":"2022","unstructured":"Schilsky ML, Czlonkowska A, Zuin M, Cassiman D, Twardowschy C, Poujois A, Gondim FAA, Denk G, Cury RG, Ott P, et al. Trientine tetrahydrochloride versus penicillamine for maintenance therapy in Wilson disease (CHELATE): a randomised, open-label, non-inferiority, phase 3 trial. Lancet Gastroenterol Hepatol. 2022;7(12):1092\u2013102.","journal-title":"Lancet Gastroenterol Hepatol"},{"issue":"12","key":"4310_CR27","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1007\/s40265-024-02099-0","volume":"84","author":"COF Kamlin","year":"2024","unstructured":"Kamlin COF, T MJ. Trientine Tetrahydrochloride, From Bench to Bedside: A Narrative Review. Drugs. 2024;84(12):1509\u201318.","journal-title":"Drugs"},{"issue":"4","key":"4310_CR28","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1007\/s11096-018-0657-1","volume":"40","author":"G Fornasier","year":"2018","unstructured":"Fornasier G, Francescon S, Leone R, Baldo P. An historical overview over Pharmacovigilance. Int J Clin Pharm. 2018;40(4):744\u20137.","journal-title":"Int J Clin Pharm"},{"issue":"Suppl 2","key":"4310_CR29","doi-asserted-by":"publisher","first-page":"S66","DOI":"10.21037\/atm.2019.03.18","volume":"7","author":"P Hedera","year":"2019","unstructured":"Hedera P. Clinical management of Wilson disease. Ann Transl Med. 2019;7(Suppl 2):S66.","journal-title":"Ann Transl Med"},{"issue":"4","key":"4310_CR30","doi-asserted-by":"publisher","first-page":"1464","DOI":"10.1002\/hep.30280","volume":"69","author":"P Ferenci","year":"2019","unstructured":"Ferenci P, Stremmel W, Czlonkowska A, Szalay F, Viveiros A, Stattermayer AF, Bruha R, Houwen R, Pop TL, Stauber R, et al. Age and Sex but Not ATP7B Genotype Effectively Influence the Clinical Phenotype of Wilson Disease. Hepatology. 2019;69(4):1464\u201376.","journal-title":"Hepatology"},{"key":"4310_CR31","doi-asserted-by":"publisher","first-page":"1176946","DOI":"10.3389\/fneur.2023.1176946","volume":"14","author":"L Cai","year":"2023","unstructured":"Cai L, Huang X, Ye Y, Yang D, Xie L, Fu D, Peng L, Zhou D, Liao J. Role of gender and age in features of Wilson\u2019s disease. Front Neurol. 2023;14:1176946.","journal-title":"Front Neurol"},{"issue":"7","key":"4310_CR32","doi-asserted-by":"publisher","first-page":"1372","DOI":"10.1016\/j.dld.2025.04.008","volume":"57","author":"L Lapenna","year":"2025","unstructured":"Lapenna L, Merli M, Cilla M, Cossiga V, Floreani A, Invernizzi F, Toniutto P, Burra P. Special Interest Group Gender in Hepatology of the Italian Association for the Study of the L: Sex differences in hepatic encephalopathy: addressing the knowledge gap. Dig Liver Dis. 2025;57(7):1372\u20136.","journal-title":"Dig Liver Dis"},{"key":"4310_CR33","doi-asserted-by":"crossref","unstructured":"Antos A, Czlonkowska A, Bembenek J, Kurkowska-Jastrzebska I, Litwin T. D-Penicillamine-Induced Myasthenia Gravis-A probable complication of Wilson\u2019s disease treatment-a case report and systematic review of the literature. Life (Basel) 2023, 13(8).","DOI":"10.3390\/life13081715"},{"issue":"2","key":"4310_CR34","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1002\/art.1780230205","volume":"23","author":"WF Kean","year":"1980","unstructured":"Kean WF, Dwosh IL, Anastassiades TP, Ford PM, Kelly HG. The toxicity pattern of D-penicillamine therapy. A guide to its use in rheumatoid arthritis. Arthritis Rheum. 1980;23(2):158\u201364.","journal-title":"Arthritis Rheum"},{"issue":"4","key":"4310_CR35","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1016\/0049-0172(86)90023-5","volume":"15","author":"HB Stein","year":"1986","unstructured":"Stein HB, Schroeder ML, Dillon AM. Penicillamine-induced proteinuria: risk factors. Semin Arthritis Rheum. 1986;15(4):282\u20137.","journal-title":"Semin Arthritis Rheum"},{"key":"4310_CR36","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1016\/0002-9343(64)90096-8","volume":"36","author":"DA Adams","year":"1964","unstructured":"Adams DA, Goldman R, Maxwell MH, Latta H. Nephrotic Syndrome Associated with Penicillamine Therapy of Wilson\u2019s Disease. Am J Med. 1964;36:330\u20136.","journal-title":"Am J Med"},{"issue":"12","key":"4310_CR37","doi-asserted-by":"publisher","first-page":"1311","DOI":"10.1001\/jama.1966.03110250125039","volume":"198","author":"I Sternlieb","year":"1966","unstructured":"Sternlieb I. Penicillamine and the nephrotic syndrome. JAMA. 1966;198(12):1311\u20132.","journal-title":"JAMA"},{"issue":"4","key":"4310_CR38","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1007\/BF02086822","volume":"11","author":"P Jezersek","year":"1979","unstructured":"Jezersek P, Ferluga D. Nephrotic syndrome induced by D-penicillamine therapy. Int Urol Nephrol. 1979;11(4):349\u201361.","journal-title":"Int Urol Nephrol"},{"issue":"7","key":"4310_CR39","doi-asserted-by":"publisher","first-page":"1487","DOI":"10.1001\/archinte.1983.00350070215039","volume":"143","author":"JM Trice","year":"1983","unstructured":"Trice JM, Pinals RS, Plitman GI. Thrombotic thrombocytopenic purpura during penicillamine therapy in rheumatoid arthritis. Arch Intern Med. 1983;143(7):1487\u20138.","journal-title":"Arch Intern Med"},{"issue":"5","key":"4310_CR40","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1001\/archneur.1972.00490110108011","volume":"26","author":"GT Strickland","year":"1972","unstructured":"Strickland GT. Febrile penicillamine eruption. Arch Neurol. 1972;26(5):474.","journal-title":"Arch Neurol"},{"issue":"8","key":"4310_CR41","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1016\/j.cgh.2013.03.012","volume":"11","author":"KH Weiss","year":"2013","unstructured":"Weiss KH, Thurik F, Gotthardt DN, Schafer M, Teufel U, Wiegand F, Merle U, Ferenci-Foerster D, Maieron A, Stauber R, et al. Efficacy and safety of oral chelators in treatment of patients with Wilson disease. Clin Gastroenterol Hepatol. 2013;11(8):1028\u2013e10351021.","journal-title":"Clin Gastroenterol Hepatol"},{"key":"4310_CR42","unstructured":"Trientine Hydrochloride (Waymade-Trientine). CADTH Reimbursement Recommendation: Indication: For the treatment of patients with Wilson disease who are intolerant to penicillamine [https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK599005\/]."},{"issue":"5","key":"4310_CR43","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1080\/14740338.2023.2219892","volume":"22","author":"S Crisafulli","year":"2023","unstructured":"Crisafulli S, Khan Z, Karatas Y, Tuccori M, Trifiro G. An overview of methodological flaws of real-world studies investigating drug safety in the post-marketing setting. Expert Opin Drug Saf. 2023;22(5):373\u201380.","journal-title":"Expert Opin Drug Saf"},{"issue":"9","key":"4310_CR44","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1007\/s40264-025-01548-3","volume":"48","author":"S Crisafulli","year":"2025","unstructured":"Crisafulli S, Bate A, Brown JS, Candore G, Chandler RE, Hammad TA, Lane S, Maro JC, Noren GN, Pariente A, et al. Interplay of Spontaneous Reporting and Longitudinal Healthcare Databases for Signal Management: Position Statement from the Real-World Evidence and Big Data Special Interest Group of the International Society of Pharmacovigilance. Drug Saf. 2025;48(9):959\u201376.","journal-title":"Drug Saf"},{"issue":"1","key":"4310_CR45","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1186\/s13023-018-0942-z","volume":"13","author":"M Garcia","year":"2018","unstructured":"Garcia M, Downs J, Russell A, Wang W. Impact of biobanks on research outcomes in rare diseases: a systematic review. Orphanet J Rare Dis. 2018;13(1):202.","journal-title":"Orphanet J Rare Dis"},{"issue":"3","key":"4310_CR46","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1007\/s11096-024-01709-x","volume":"46","author":"L Silva","year":"2024","unstructured":"Silva L, Pacheco T, Araujo E, Duarte RJ, Ribeiro-Vaz I, Ferreira-da-Silva R. Unveiling the future: precision pharmacovigilance in the era of personalized medicine. Int J Clin Pharm. 2024;46(3):755\u201360.","journal-title":"Int J Clin Pharm"},{"issue":"6","key":"4310_CR47","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1002\/sim.8445","volume":"39","author":"LJ Beesley","year":"2020","unstructured":"Beesley LJ, Salvatore M, Fritsche LG, Pandit A, Rao A, Brummett C, Willer CJ, Lisabeth LD, Mukherjee B. The emerging landscape of health research based on biobanks linked to electronic health records: Existing resources, statistical challenges, and potential opportunities. Stat Med. 2020;39(6):773\u2013800.","journal-title":"Stat Med"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13023-026-04310-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-026-04310-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-026-04310-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T19:41:02Z","timestamp":1781638862000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s13023-026-04310-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,9]]},"references-count":47,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4310"],"URL":"https:\/\/doi.org\/10.1186\/s13023-026-04310-9","relation":{},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,9]]},"assertion":[{"value":"14 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Ethics approval was not required for this study, as it was based on publicly accessible pharmacovigilance databases (FAERS and VigiAccess) that contain anonymized case reports. Written informed consent from participants was not required in accordance with national legislation and institutional guidelines.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"153"}}