{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T18:43:39Z","timestamp":1773254619822,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Differences in performance of the Self\u2010Controlled Case Series (SCCS) for signal detection have been reported across different databases. However, there has been limited comparative analysis of performance and it remains unknown whether combinations of databases could enable more effective signal detection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study aims to compare the performance of the SCCS for signal detection across several data sources, and to determine whether combinations of databases can improve SCCS performance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We applied the SCCS to macrolides and fluoroquinolone antibiotics, in four databases: Merative MarketScan Commercial Claims and Medicare, the Clinical Practice Research Datalink (CPRD) Aurum and the Syst\u00e8me National des Donn\u00e9es de Sant\u00e9. We developed a reference set of 104 positive controls and 58 negative controls, using a taxonomy framework to ensure the selected drug outcome pairs are theoretically well suited to the SCCS design. The observation period lasted 2\u2009years, with a 30\u2010day risk\u2010window after each dispensing. Diagnostic performance was measured using sensitivity, specificity and area under the receiver operating curve (AUC) with respect to the product labels, both for individual and combinations of databases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The sensitivity of the SCCS ranged from 0.57\u20130.89 across individual databases, and the specificity from 0.43\u20130.77 when limited to drug\u2010outcome pairs sufficiently powered. The combination of all databases achieved the maximum sensitivity of 0.89 (0.41 specificity) for the full reference set, and a sensitivity of 1 (0.35 specificity) for drug outcome pairs with enough power. Whilst AUCs ranged from 0.66 to 0.71 across individual databases, the highest performing combination was CPRD plus MarketScan Commercial Claims (0.76 AUC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Using a carefully designed reference set of drug\u2010outcome pairs well suited to the study design, the SCCS performance varied substantially by database due to differences in population, reporting, healthcare and coding systems and prescribing patterns. Multi\u2010database studies showed increased performance of SCCS for signal detection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pds.70298","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T04:25:17Z","timestamp":1770956717000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Performance of the Self\u2010Controlled Case Series for Drug Safety Signal Detection: A Multi\u2010Database Study"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4207-7447","authenticated-orcid":false,"given":"Astrid","family":"Coste","sequence":"first","affiliation":[{"name":"Department of Non\u2010Communicable Diseases Epidemiology LSHTM  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8618-7333","authenticated-orcid":false,"given":"Angel Y. S.","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Non\u2010Communicable Diseases Epidemiology LSHTM  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francois","family":"Haguinet","sequence":"additional","affiliation":[{"name":"GSK  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3151-3653","authenticated-orcid":false,"given":"Andrew","family":"Bate","sequence":"additional","affiliation":[{"name":"Department of Non\u2010Communicable Diseases Epidemiology LSHTM  London UK"},{"name":"GSK  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian J.","family":"Douglas","sequence":"additional","affiliation":[{"name":"Department of Non\u2010Communicable Diseases Epidemiology LSHTM  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwae226\/7714794"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2172"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jval.2020.04.002"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.3439"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.70028"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.70042"},{"key":"e_1_2_9_8_1","article-title":"Strengths and Limits of Claims and EHR\u2010Based Data Sources","author":"Sentinel Community Building and Outreach Center","year":"2023","journal-title":"Pharmacoepidemiology and Drug Safety"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.5620"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40264-013-0109-8"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40264-013-0106-y"},{"key":"e_1_2_9_12_1","first-page":"206","article-title":"Methods for Drug Safety Signal Detection Using Routinely Collected Electronic Healthcare Data: A Systematic Review","volume":"31","author":"Coste A.","year":"2022","journal-title":"Pharmacoepidemiology and Drug Safety"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40264-023-01382-5"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2020-037405"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyz034"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2017.09.022"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40264-013-0108-9"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.5038"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.5161"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40264-013-0100-4"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1833"},{"key":"e_1_2_9_22_1","unstructured":"S. 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