{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T01:20:56Z","timestamp":1787620856717,"version":"build-2736575974"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"2","funder":[{"name":"VA HSR","award":["RCS 10-391, RCS 21-136"],"award-info":[{"award-number":["RCS 10-391, RCS 21-136"]}]},{"DOI":"10.13039\/100000038","name":"US Food and Drug Administration","doi-asserted-by":"crossref","award":["75F40121S30013"],"award-info":[{"award-number":["75F40121S30013"]}],"id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"crossref"}]},{"name":"US Department of Veterans Affairs Cooperative Studies Program and funded in part by the Department of Health and Human Services, Biomedical Advanced Research and Development Authority","award":["AAI21050"],"award-info":[{"award-number":["AAI21050"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In a well-designed clinical trial, time zero is when eligibility is determined, treatment is assigned, follow-up time begins, and each of these elements is aligned. Attaining this alignment can be challenging in observational studies, risking potential bias. We compared the impact of different time zero designations on the estimated effectiveness of nirmatrelvir-ritonavir for COVID-19. We identified US veterans who tested positive for SARS-CoV-2 from April 2022 to March 2023 and compared nirmatrelvir-ritonavir vs no treatment using 5 time zero approaches: (1a) test-date (treated) vs test-date (untreated) allowing treatment on days 0-5 with matching, (1b) day 0 only with matching, or (1c) days 0-5 with a clone-censor-weight method; (2) treatment date vs test-date with matching; or (3) treatment date vs matched index date. Thirty-day incidence of hospitalization or death was lower in the nirmatrelvir-ritonavir group than the no treatment group for all time zero approaches. Estimated risk differences (95% CI) were larger for approaches 1a (\u22122.10% [\u22122.35 to \u22121.86]), 1b (\u22122.03% [\u22122.40 to \u22121.84]), and 2 (\u22122.26% [\u22122.47 to \u22122.02]); \u22121.80% (\u22121.89 to \u22121.45) for approach 3; and lowest for approach 1c (\u22120.95% [\u22121.11 to \u22120.75]). Different time zero designations can influence effect estimates and should be carefully considered when designing pharmacoepidemiology studies.<\/jats:p>","DOI":"10.1093\/aje\/kwaf221","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T11:54:20Z","timestamp":1760097260000},"page":"562-568","source":"Crossref","is-referenced-by-count":2,"title":["Impact of time zero designation on estimated COVID-19 antiviral effectiveness in observational studies"],"prefix":"10.1093","volume":"195","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3229-5590","authenticated-orcid":false,"given":"Kristina L","family":"Bajema","sequence":"first","affiliation":[{"name":"Veterans Affairs Portland Health Care System , Portland, OR ,","place":["United States"]},{"name":"Division of Infectious Diseases, Department of Medicine, Oregon Health and Science University , Portland, OR ,","place":["United 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States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nallakkandi","family":"Rajeevan","sequence":"additional","affiliation":[{"name":"Veterans Affairs Cooperative Studies Program Clinical Epidemiology Research Center (CSP CERC), Veterans Affairs Connecticut Health Care System , West Haven, CT ,","place":["United States"]},{"name":"Biomedical Informatics and Data Science, Yale School of Medicine , New Haven, CT ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1765-5938","authenticated-orcid":false,"given":"Matthew L","family":"Maciejewski","sequence":"additional","affiliation":[{"name":"Center of Innovation to Accelerate Discovery and Practice Transformation, Durham Veterans Affairs Medical Center , Durham, NC ,","place":["United States"]},{"name":"Department of Population Health Sciences, Duke University School of Medicine , Durham, NC ,","place":["United States"]},{"name":"Department of Medicine, Duke University , Durham, NC ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5170-9819","authenticated-orcid":false,"given":"Valerie A","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Population Health Sciences, Duke University School of Medicine , Durham, NC ,","place":["United States"]},{"name":"Department of Medicine, Duke University , Durham, NC ,","place":["United States"]},{"name":"Department of Biostatistics and Bioinformatics, Duke University , Durham, NC ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy S B","family":"Bohnert","sequence":"additional","affiliation":[{"name":"VA Health Services Research and Development, Center for Clinical Management and Research, VA Ann Arbor Health Care System , Ann Arbor, MI ,","place":["United States"]},{"name":"Department of Anesthesiology, University of Michigan , Ann Arbor, MI ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6436-7157","authenticated-orcid":false,"given":"Denise M","family":"Hynes","sequence":"additional","affiliation":[{"name":"Center of Innovation to Improve Veteran Involvement in Care (CIVIC), Veterans Affairs Portland Health Care System , Portland, OR ,","place":["United States"]},{"name":"Health Management and Policy, College of Health, Center for Quantitative Life Sciences, Oregon State University , Corvallis, OR ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihaela","family":"Aslan","sequence":"additional","affiliation":[{"name":"Veterans Affairs Cooperative Studies Program Clinical Epidemiology Research Center (CSP CERC), Veterans Affairs Connecticut Health Care System , West Haven, CT ,","place":["United States"]},{"name":"Office of Research and Development , Washington, DC ,","place":["United 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