{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T13:13:27Z","timestamp":1781702007811,"version":"3.54.5"},"reference-count":32,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>The aim of this is to test the feasibility of identifying unsuspected, previously unknown drug\u2010outcome associations, that is, collateral drug benefits (CDBs), through a systematic screening analysis of real\u2010world health\u2010care databases. Ultimately, such screening could lead to drug repurposing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analysed data from the Danish National Prescription Registry and the Danish Patient Registry, covering 1996\u20132022. The study employed the sequence symmetry analysis (SSA), an exposure\u2010anchored self\u2010controlled design that compares the number of clinical outcomes in symmetrical windows before and after the exposure drug initiation. To verify the directionality and robustness of these associations, we incorporated the case\u2010crossover (CCO) design, another self\u2010controlled design. The obtained associations were ranked according to the hypothetical number of averted outcomes, if a causal effect could be assumed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The analysis included 1.3 billion prescriptions and 260 million diagnosis records, resulting in 27\u2009820\u2009976 drug\u2013diagnosis combinations and 7\u2009920\u2009323 drug\u2013drug combinations. Preventive associations in both the SSA and CCO were found in 7795 drug\u2013diagnosis and 5088 drug\u2013drug combinations. A manual review of the highest ranked 100 associations resulted in 11 drug\u2013diagnosis and 2 drug\u2013drug associations as potential unknown CDBs. Notable findings included selective serotonin reuptake inhibitors linked to a lower risk of certain cardiovascular outcomes, anticholinesterases associated with fewer delirium diagnoses and progestogens associated with a reduced risk of obesity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The study confirms that hypothesis\u2010free screening is feasible and that combining sequence symmetry analysis and case\u2010crossover designs can identify potential collateral drug benefits. Further validation studies are required to confirm these findings and explore their clinical implications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70427","type":"journal-article","created":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T04:34:21Z","timestamp":1766205261000},"page":"1614-1624","source":"Crossref","is-referenced-by-count":1,"title":["Screening real\u2010world data for evidence of unsuspected drug benefits: An application of the sequence symmetry analysis"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7506-3426","authenticated-orcid":false,"given":"Martin Torp","family":"Rahbek","sequence":"first","affiliation":[{"name":"Clinical Pharmacology, Pharmacy and Environmental Medicine University of Southern Denmark  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars Christian","family":"Lund","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology, Pharmacy and Environmental Medicine University of Southern Denmark  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesper","family":"Hallas","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology, Pharmacy and Environmental Medicine University of Southern Denmark  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.5905.440"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0049\u20100172(10)80012\u20105"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1468"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2018.168"},{"key":"e_1_2_9_6_1","first-page":"537","volume-title":"The organic chemistry of drug design and drug action","author":"Silverman RB","year":"2014"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.31887\/DCNS.2006.8.3\/tban"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1204524109"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.5673"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10654\u2010018\u20100386\u20108"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/1403494810394717"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.2147\/CLEP.S91125"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10654\u2010014\u20109930\u20103"},{"key":"e_1_2_9_14_1","unstructured":"English \u2013 Sundhedsdatastyrelsen retrieved November 1 2024 https:\/\/sundhedsdatastyrelsen.dk\/da\/english"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.5774"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.1736"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10654\u2010017\u20100281\u20108"},{"key":"e_1_2_9_18_1","unstructured":"World Health Organization International statistical classification of diseases and related health problems 10th revision Fifth edition 2016. 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