{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T22:57:51Z","timestamp":1778540271689,"version":"3.51.4"},"reference-count":33,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,11,26]],"date-time":"2018-11-26T00:00:00Z","timestamp":1543190400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["1504916"],"award-info":[{"award-number":["1504916"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Surveillance of medication use in pregnancy is essential to identify associations between first trimester medications and congenital anomalies (CAs). Medications in the same Anatomical Therapeutic Chemical classes may have similar effects. We aimed to use this information to improve the detection of potential teratogens in CA surveillance data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data on 15\u2009058 malformed fetuses with first trimester medication exposures from 1995\u20132011 were available from EUROmediCAT, a network of European CA registries. For each medication\u2010CA combination, the proportion of the CA in fetuses with the medication was compared to the proportion of the CA in all other fetuses in the dataset. The Australian classification system was used to identify <jats:italic>high\u2010risk<\/jats:italic> medications in order to compare two methods of controlling the false discovery rate (FDR): a <jats:italic>single<\/jats:italic> FDR applied across all combinations, and a <jats:italic>double<\/jats:italic> FDR incorporating groupings of medications.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There were 28\u2009765 potential combinations (523 medications \u00d7 55 CAs) for analysis. An FDR cut\u2010off of 50% resulted in a reasonable effective workload, for which single FDR gave rise to eight medication signals (three <jats:italic>high\u2010risk<\/jats:italic> medications) and double FDR 50% identified 16 signals (six <jats:italic>high\u2010risk<\/jats:italic>). Over a range of FDR cut\u2010offs, double FDR identified more <jats:italic>high\u2010risk<\/jats:italic> medications as signals, for comparable effective workloads.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The double FDR method appears to improve the detection of potential teratogens in comparison to the single FDR, while maintaining a low risk of false positives. Use of double FDR is recommended in routine signal detection analyses of CA data.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13799","type":"journal-article","created":{"date-parts":[[2018,10,23]],"date-time":"2018-10-23T10:44:31Z","timestamp":1540291471000},"page":"356-365","source":"Crossref","is-referenced-by-count":4,"title":["Identifying signals of potentially harmful medications in pregnancy: use of the double false discovery rate method to adjust for multiple testing"],"prefix":"10.1111","volume":"85","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5709-367X","authenticated-orcid":false,"given":"Alana","family":"Cavadino","sequence":"first","affiliation":[{"name":"Wolfson Institute of Preventive Medicine Queen Mary University of London  UK"},{"name":"Section of Epidemiology and Biostatistics, School of Population Health University of Auckland  New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Prieto\u2010Merino","sequence":"additional","affiliation":[{"name":"Department of Medical Statistics London School of Hygiene and Tropical Medicine  London UK"},{"name":"Applied Statistics in Medical Research Group Catholic University of Murcia (UCAM)  Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joan K.","family":"Morris","sequence":"additional","affiliation":[{"name":"Wolfson Institute of Preventive Medicine Queen Mary University of London  UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,11,26]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2013-004365"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.2184"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420200205"},{"key":"e_1_2_10_5_1","first-page":"S46","article-title":"EUROmediCAT: European surveillance of safety of medication use in pregnancy","volume":"20","author":"Jong\u2010van den Berg L","year":"2011","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13056"},{"key":"e_1_2_10_7_1","unstructured":"WHO Collaborating Centre for Drug Statistics Methodology.\u2009ATC structure and principles. 2011 2011\u201003\u201025. Available athttp:\/\/www.whocc.no\/atc\/structure_and_principles\/(last accessed 21 April 2016)."},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1191\/0962280204sm363ra"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.5310"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20779"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20775"},{"key":"e_1_2_10_12_1","unstructured":"EUROCAT Central Registry.\u2009EUROCAT Guide 1.4: Instructions for the registration and surveillance of congenital anomalies. 2013 EUROCAT Central Registry University of Ulster."},{"key":"e_1_2_10_13_1","unstructured":"BakkerM LdJ.\u2009EUROCAT Special Report: Sources of Information on Medication Use in Pregnancy.2014. Available athttp:\/\/www.eurocat\u2010network.eu\/content\/Special\u2010Report\u2010Medication\u2010Use\u2010In\u2010Pregnancy.pdf(last accessed 11 August 2016)."},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20780"},{"key":"e_1_2_10_15_1","unstructured":"WHO Collaborating Centre for Drug Statistics Methodology.\u2009ATC alterations from 1982\u20102016.201518 December 2015. Available athttp:\/\/www.whocc.no\/atc_ddd_alterations__cumulative\/atc_alterations\/(last accessed 11 August 2016)."},{"key":"e_1_2_10_16_1","volume-title":"Stata Statistical Software: Release 12","author":"StataCorp","year":"2011"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"e_1_2_10_18_1","unstructured":"Australian Government Department of Health.\u2009Prescribing medicines in pregnancy database.2016. 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