{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T12:47:26Z","timestamp":1793450846968,"version":"4.5.0"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Observational studies in critical care medicine offer a popular and practical approach to questions of treatment effectiveness. Although observational research is widely understood to be susceptible to design and interpretation challenges, one well-described source of bias\u2014immortal time bias (ITB)\u2014is frequently present yet often overlooked. ITB may be introduced by study design oversights or mishandled during data analysis. When present, ITB can create inappropriate estimates of the benefit or harm of an exposure or intervention. Studies examining treatments in critically ill patients may be particularly susceptible to ITB, with consequences for clinical adoption and design and initiation of randomized trials. In this Critical Care Perspective, we illustrate the persistent problem of ITB in observational research using recent studies of hydrocortisone, ascorbic acid, and thiamine therapy in patients with sepsis and septic shock. Of the eight studies examined, none contained enough design or reporting elements to rule out the presence of ITB. To mitigate the influence of ITB in future observational studies, we present a novel checklist to help readers assess the features of study design, analysis, and reporting that introduce ITB or obscure its presence. We recommend that commonly used tools designed to evaluate observational research studies should include an ITB assessment.<\/jats:p>","DOI":"10.1164\/rccm.202008-3238cp","type":"journal-article","created":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T18:38:08Z","timestamp":1616611088000},"page":"1222-1229","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":47,"title":["Attention to Immortal Time Bias in Critical Care Research"],"prefix":"10.1093","volume":"203","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1849-5780","authenticated-orcid":false,"given":"Emily A.","family":"Vail","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Critical Care and"},{"name":"Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7360-2489","authenticated-orcid":false,"given":"Hayley B.","family":"Gershengorn","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care, and Sleep Medicine, University of Miami Miller School of Medicine, Miami, Florida"},{"name":"Division of Critical Care Medicine, Albert Einstein College of Medicine, Bronx, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5477-8422","authenticated-orcid":false,"given":"Hannah","family":"Wunsch","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada"},{"name":"Department of Anesthesia and"},{"name":"Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4685-6894","authenticated-orcid":false,"given":"Allan J.","family":"Walkey","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Sleep and Critical Care Medicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,5,15]]},"reference":[{"key":"2026030322031429400_B1"},{"key":"2026030322031429400_B2","author":"Grady"},{"key":"2026030322031429400_B3","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1001\/jama.2019.7936","article-title":"Wide interest in a vitamin C drug cocktail for sepsis despite lagging evidence","volume":"322","author":"Rubin","year":"2019","journal-title":"JAMA"},{"key":"2026030322031429400_B4","doi-asserted-by":"crossref","first-page":"2493","DOI":"10.1001\/jama.2020.8630","article-title":"Association of treatment with hydroxychloroquine or azithromycin with in-hospital mortality in patients with COVID-19 in New York state","volume":"323","author":"Rosenberg","year":"2020","journal-title":"JAMA"},{"key":"2026030322031429400_B5","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.ijid.2020.06.099","article-title":"Treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalized with COVID-19","volume":"97","author":"Arshad","year":"2020","journal-title":"Int J Infect Dis"},{"key":"2026030322031429400_B6","doi-asserted-by":"crossref","first-page":"e474","DOI":"10.1016\/S2665-9913(20)30173-9","article-title":"Tocilizumab in patients with severe COVID-19: a retrospective cohort study","volume":"2","author":"Guaraldi","year":"2020","journal-title":"Lancet Rheumatol"},{"key":"2026030322031429400_B7","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1513\/AnnalsATS.201808-564PS","article-title":"Control of confounding and reporting of results in causal inference studies: guidance for authors from editors of respiratory, sleep, and critical care journals","volume":"16","author":"Lederer","year":"2019","journal-title":"Ann Am Thorac Soc"},{"key":"2026030322031429400_B8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jcrc.2006.01.004","article-title":"Methods to adjust for bias and confounding in critical care health services research involving observational data","volume":"21","author":"Wunsch","year":"2006","journal-title":"J Crit Care"},{"key":"2026030322031429400_B9","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1093\/aje\/kwm324","article-title":"Immortal time bias in pharmaco-epidemiology","volume":"167","author":"Suissa","year":"2008","journal-title":"Am J Epidemiol"},{"key":"2026030322031429400_B10","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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