{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T21:30:45Z","timestamp":1790112645412,"version":"4.0.1"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,1,10]],"date-time":"2020-01-10T00:00:00Z","timestamp":1578614400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>In self\u2010controlled case series (SCCS), the event should not condition the probability of subsequent exposure. If this assumption is not met, an important bias could take place. The association of hip\/femur fracture (HFF) and use of benzodiazepines (BDZ) has a bidirectional causal relationship and can serve as case study to investigate the impact of this methodological issue.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To assess the magnitude of bias introduced in a SCCS when HFF conditions the posterior exposure to BDZ and explore ways to correct it.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Four thousand four hundred fifty cases of HFF who had at least one BZD prescription were selected from the primary care health record database BIFAP. Exposure to BZD was divided into non\u2010use, current, recent, and past use. Conditional Poisson regression was used to estimate incidence rate ratios (IRRs) of HFF among current vs non\u2010use\/past, adjusted for age. To investigate possible event\u2010exposure dependence, a pre\u2010exposure time of different lengths (15, 30, and 60\u2009days) was excluded from the reference category to evaluate the IRR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>IRR of HHF for current use was 0.79 (0.72\u20100.86); removing 30\u2009days, IRR was 1.43 (1.31\u20101.57). Removing 15\u2009days, IRR was 1.29 (1.18\u20101.41), and removing 60\u2009days, IRR was 1.56 (1.42\u20101.72). A pre\u2010exposure period up to 182\u2009days was necessary to remove such effect giving an IRR of 1.64 (1.48\u20101.81).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>HFF remarkably conditioned the use of BDZs resulting in seriously biased IRRs when this association was studied through a SCCS design. The use of pre\u2010exposure periods of different lengths helped to correct this error.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pds.4959","type":"journal-article","created":{"date-parts":[[2020,1,10]],"date-time":"2020-01-10T23:06:23Z","timestamp":1578697583000},"page":"388-395","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Impact of pre\u2010exposure time bias in self\u2010controlled case series when the event conditions the exposure: Hip\/femur fracture and use of benzodiazepines as a case study"],"prefix":"10.1002","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3091-786X","authenticated-orcid":false,"given":"Gema","family":"Requena","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences (Pharmacology), School of Medicine University of Alcal\u00e1 (IRYCIS)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian J.","family":"Douglas","sequence":"additional","affiliation":[{"name":"Epidemiology Deparment London School of Hygiene and Tropical Medicine (LSHTM)  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Consuelo","family":"Huerta","sequence":"additional","affiliation":[{"name":"Division of Pharmacoepidemiology and Pharmacovigilance Spanish Agency of Medicines and Medical Devices  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9119-8646","authenticated-orcid":false,"given":"Francisco","family":"de Abajo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences (Pharmacology), School of Medicine University of Alcal\u00e1 (IRYCIS)  Madrid Spain"},{"name":"Clinical Pharmacology Unit University Hospital Pr\u00edncipe de Asturias  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,1,10]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2004.01.017"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2005.041798"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-9876.2006.00554.x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.respe.2010.06.168"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.i4515"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.e4388"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1000154"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehu263"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12186"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.3822"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.5694\/mja12.11087"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40264-017-0626-y"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.7536"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-014-1676-z"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12557"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.3825"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-014-9850-y"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2009.07.001"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwn364"},{"key":"e_1_2_9_21_1","unstructured":"PROTECT\u2010EU. 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