{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:03:46Z","timestamp":1790816626883,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004489","name":"Mitacs","doi-asserted-by":"publisher","award":["IT46896"],"award-info":[{"award-number":["IT46896"]}],"id":[{"id":"10.13039\/501100004489","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Traditional pharmacovigilance detects single drug\u2013event associations but cannot readily characterize multi\u2010system adverse\u2010event patterns such as fluoroquinolone\u2010associated disability. We evaluated unsupervised machine learning for this purpose, using fluoroquinolones as an exemplar.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analysed 40\u2009127 adult fluoroquinolone primary\u2010suspect reports from the FDA Adverse Event Reporting System (FAERS, 2004\u20132025). Events were encoded as binary MedDRA Preferred Term (PT) and System Organ Class matrices; seriousness and outcome were excluded from clustering and used only post hoc. Multiple correspondence analysis with k\u2010means was primary, validated by k\u2010modes and hierarchical clustering. Cluster number (k\u2009=\u20092\u201315) was assessed by internal validity indices with bootstrap stability. Comparators were macrolides (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200939\u2009948) and amoxicillin (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200916\u2009310).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At PT level, silhouette and Calinski\u2013Harabasz indices were optimal at two clusters (Davies\u2013Bouldin at three; silhouette 0.560), separating a multi\u2010system cluster (4072 reports; 10.1%) enriched for neuropsychiatric, musculoskeletal and sensory terms (lifts: memory impairment 8.6, muscle atrophy 8.3, dry eye 7.8). Excluding seriousness and outcome left the cluster essentially unchanged (91.4% retained; \u03ba 0.95), indicating definition by event topology, not case severity; independent algorithms recovered the same subgroup across granularities. Post hoc, the cluster was disproportionately disabling (43.0%\n                      <jats:italic>vs<\/jats:italic>\n                      . 11.7%). The fixed signature classified 14.9% of fluoroquinolone reports\n                      <jats:italic>vs<\/jats:italic>\n                      . 5.3% (macrolides) and 3.9% (amoxicillin).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Unsupervised clustering of FAERS data identified, without prior clinical input, a reproducible multi\u2010system adverse\u2010event pattern among fluoroquinolone reports, potentially supporting the feasibility of unsupervised exploratory pattern detection in pharmacovigilance. Given the limitations of spontaneous reporting databases, the findings are strictly hypothesis\u2010generating.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70853","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:26:09Z","timestamp":1790814369000},"source":"Crossref","is-referenced-by-count":0,"title":["Unsupervised machine learning for multi\u2010system adverse event pattern detection in pharmacovigilance: A proof\u2010of\u2010concept analysis of fluoroquinolone reports in FAERS"],"prefix":"10.1002","author":[{"given":"Niaz","family":"Chalabianloo","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology Western University  London Ontario Canada"},{"name":"Department of Computer Science Western University  London Ontario Canada"},{"name":"ICES Western  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheikh S.","family":"Abdullah","sequence":"additional","affiliation":[{"name":"Department of Computer Science Western University  London Ontario Canada"},{"name":"ICES Western  London Ontario Canada"},{"name":"Department of Computer Science MacEwan University  Edmonton Alberta Canada"},{"name":"London Health Sciences Centre, Research Institute  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamran","family":"Sedig","sequence":"additional","affiliation":[{"name":"Department of Computer Science Western University  London Ontario Canada"},{"name":"Faculty of Information and Media Studies Western University  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4682-6564","authenticated-orcid":false,"given":"Flory T.","family":"Muanda","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Western University  London Ontario Canada"},{"name":"ICES Western  London Ontario Canada"},{"name":"Lawson Health Research Institute London Health Sciences Centre  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"U.S. Food and Drug Administration.FDA drug safety communication: FDA updates warnings for oral and injectable fluoroquinolone antibiotics due to disabling side effects.2016."},{"key":"e_1_2_10_3_1","unstructured":"European Medicines Agency.Quinolone\u2010 and fluoroquinolone\u2010containing medicinal products. 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