{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T00:07:18Z","timestamp":1758931638504,"version":"3.44.0"},"reference-count":16,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,7,6]],"date-time":"2025-07-06T00:00:00Z","timestamp":1751760000000},"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":["Evaluation Clinical Practice"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Databases of reported adverse events after vaccination are used to detect alarming signals by qualitative methods (case series) and quantitative methods (the proportional reporting ratio).<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>This methodological\u2010empirical paper explores several key questions: How useful are these databases for detecting alarming signals? To which study design do they correspond? Which measure of association should be computed? Which key biases might operate, and what can be done to avoid or reduce them?<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A contemporary methodological tool\u2014causal diagrams\u2014was used to answer these questions. The analytical approach was demonstrated for three possible outcomes of Covid vaccines: Thrombosis with Thrombocytopenia Syndrome, Guillain\u2010Barr\u00e9 Syndrome, and reported death.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A database of reported adverse events corresponds to a case\u2010control study and should be analysed accordingly. The preferred measure of association is the odds ratio, not the proportional reporting ratio. Reporting bias operates to overestimate the true odds ratio, whereas control selection bias operates in the opposite direction (underestimation). As illustrated by three examples of reported death, the magnitude of the biases depends on the choice of the reference vaccine. However, extended methodological and empirical work is needed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Databases of reported adverse events after vaccination are a rich source for quantitative research, provided that several methodological guidelines are followed. These databases should be analysed according to the principles of a case\u2010control study, and the inference should be drawn on a case\u2010by\u2010case basis. It is crucial to estimate the reporting accuracy of a particular event by the type of vaccine, and only a clinical evaluation of a sample of records can provide this information.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jep.70188","type":"journal-article","created":{"date-parts":[[2025,7,6]],"date-time":"2025-07-06T15:54:25Z","timestamp":1751817265000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Analysing Adverse Event Databases: Principles, Challenges, and Examples"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-1670-0830","authenticated-orcid":false,"given":"Eyal","family":"Shahar","sequence":"first","affiliation":[{"name":"Mel &amp; Enid Zuckerman College of Public Health University of Arizona  Tucson Arizona USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,7,6]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.1001"},{"volume-title":"Modern Epidemiology","year":"2008","author":"Rothman K. J.","key":"e_1_2_7_3_1"},{"volume-title":"Topics in Epidemiology and Statistics","year":"2025","author":"Shahar E.","key":"e_1_2_7_4_1"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.2307\/3002000"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1515\/ijb-2016-0055"},{"volume-title":"Causal Diagrams and Three Pairs of Biases,\u201d in Epidemiology \u2010 Current Perspectives on Research and Practice","year":"2012","author":"Shahar E.","key":"e_1_2_7_7_1"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ph.1900442"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2753.2008.01031.x"},{"key":"e_1_2_7_10_1","unstructured":"United States Department of Health and Human Services (DHHS) Public Health Service (PHS) Centers for Disease Control (CDC)\/Food and Drug Administration (FDA) Vaccine Adverse Event Reporting System (VAERS) 1990 \u2010 12\/27\/2024 CDC WONDER On\u2010line Database accessed January 30 2025 http:\/\/wonder.cdc.gov\/vaers.html."},{"key":"e_1_2_7_11_1","unstructured":"https:\/\/www.cdc.gov\/vaccine-safety\/vaccines\/covid-19.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fvaccines%2Fsafety%2Fsafety-of-vaccines.html#cdc_generic_section_6-a-closer-look-at-the-safety-data accessed January 29 2025."},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajem.2021.05.054"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.16496"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2022.53845"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.15740"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0000000000001207"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/19466315.2020.1764862"}],"container-title":["Journal of Evaluation in Clinical Practice"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jep.70188","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T11:09:48Z","timestamp":1758884988000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jep.70188"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,6]]},"references-count":16,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1111\/jep.70188"],"URL":"https:\/\/doi.org\/10.1111\/jep.70188","archive":["Portico"],"relation":{},"ISSN":["1356-1294","1365-2753"],"issn-type":[{"type":"print","value":"1356-1294"},{"type":"electronic","value":"1365-2753"}],"subject":[],"published":{"date-parts":[[2025,7,6]]},"assertion":[{"value":"2025-02-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70188"}}