{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:56:26Z","timestamp":1792457786651,"version":"4.5.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T00:00:00Z","timestamp":1742256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["222098\/Z\/20\/Z"],"award-info":[{"award-number":["222098\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"UK Medical Research Council","doi-asserted-by":"publisher","award":["MR\/P022081\/1"],"award-info":[{"award-number":["MR\/P022081\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Immortal time bias is a spurious or exaggerated protective association that commonly arises in naive analyses of observational data. It occurs when people receive the intervention because they survive, rather than survive because they received the intervention. Studies in conditions with substantial early mortality, such as acute severe infections, are particularly vulnerable.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We developed IMMORTOOL, an R package accessible via a user-friendly web interface (https:\/\/petedodd.github.io\/IMMORTOOL-live\/). This tool will estimate the potential for immortal time bias using empiric or assumed data on the distributions of time to intervention and time to event. Assumptions are that no other biases are present and that the intervention does not affect the outcome. The tool was benchmarked using studies presenting both naive analyses and analyses with the intervention fit as a time-varying exposure. We applied IMMORTOOL to a set of influential observational studies that used naive analyses when estimating the impact of polyclonal intravenous immunoglobulin (IVIG) on survival in streptococcal toxic shock syndrome (STSS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>IMMORTOOL demonstrated that published estimates suggesting a survival advantage from giving IVIG in STSS are explained, at least in part, by immortal time bias.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>IMMORTOOL can quantify the potential for immortal time bias in observational analyses. Importantly, it simulates only bias resulting from misallocation of person-time, not other related selection biases. The tool may help readers interrogate published studies. We do not advocate IMMORTOOL being used to justify naive analyses where robust analyses are possible. To what extent giving IVIG in STSS improves survival remains uncertain.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ofid\/ofaf173","type":"journal-article","created":{"date-parts":[[2025,3,15]],"date-time":"2025-03-15T16:15:44Z","timestamp":1742055344000},"source":"Crossref","is-referenced-by-count":5,"title":["Quantifying Potential Immortal Time Bias in Observational Studies in Acute Severe Infection"],"prefix":"10.1093","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6081-1767","authenticated-orcid":false,"given":"Tom A","family":"Yates","sequence":"first","affiliation":[{"name":"Institute of Health Informatics, University College London , London ,","place":["UK"]},{"name":"Division of Infection and Immunity, University College London , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1163-8654","authenticated-orcid":false,"given":"Tom","family":"Parks","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Imperial College London , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5825-9347","authenticated-orcid":false,"given":"Peter J","family":"Dodd","sequence":"additional","affiliation":[{"name":"Sheffield Centre for Health and Related Research, University of Sheffield , Sheffield ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,3,18]]},"reference":[{"key":"2025052712091807100_ofaf173-B1","volume-title":"Vital statistics: a memorial volume of selections from the reports and writings of William Farr","author":"Farr","year":"1885"},{"key":"2025052712091807100_ofaf173-B2","doi-asserted-by":"crossref","first-page":"815","DOI":"10.7326\/0003-4819-76-5-815","article-title":"Does cardiac transplantation prolong life? 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