{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T02:59:48Z","timestamp":1771210788853,"version":"3.50.1"},"reference-count":32,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:00:00Z","timestamp":1741737600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DMS1915829"],"award-info":[{"award-number":["DMS1915829"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI068635"],"award-info":[{"award-number":["AI068635"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R37AI054165"],"award-info":[{"award-number":["R37AI054165"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Statistics in Medicine"],"published-print":{"date-parts":[[2025,3,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Based on data from a randomized, controlled vaccine efficacy trial, this article develops statistical methods for assessing vaccine efficacy (VE) to prevent COVID\u201019 infections by a discrete set of genetic strains of SARS\u2010CoV\u20102. Strain\u2010specific VE adjusting for possibly time\u2010varying covariates is estimated using augmented inverse probability weighting to address missing viral genotypes under a competing risks model that allows separate baseline hazards for different risk groups. Hypothesis tests are developed to assess whether the vaccine provides at least a specified level of VE against some viral genotypes and whether VE varies across genotypes. Asymptotic properties providing analytic inferences are derived and finite\u2010sample properties of the estimators and hypothesis tests are studied through simulations. This research is motivated by the fact that previous analyses of COVID\u201019 vaccine efficacy did not account for missing genotypes, which can cause severe bias and efficiency loss. The theoretical properties and simulations demonstrate superior performance of the new methods. Application to the Moderna COVE trial identifies several SARS\u2010CoV\u20102 genotype features with differential vaccine efficacy across genotypes, including lineage (Reference, Epsilon, Gamma, Zeta), indicators of residue match vs. mismatch to the vaccine\u2010strain residue at Spike amino acid positions (identifying signatures of differential VE), and a weighted Hamming distance to the vaccine strain. The results show VE decreases against genotypes more distant from the vaccine strain, highlighting the need to update COVID\u201019 vaccine strains.<\/jats:p>","DOI":"10.1002\/sim.10345","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T15:26:36Z","timestamp":1741793196000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Estimation and Hypothesis Testing of Strain\u2010Specific Vaccine Efficacy With Missing Strain Types With Application to a COVID\u201019 Vaccine Trial"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6701-7873","authenticated-orcid":false,"given":"Fei","family":"Heng","sequence":"first","affiliation":[{"name":"Department of Mathematics and Statistics University of North Florida  Jacksonville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanqing","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Mathematics and Statistics University of North Carolina at Charlotte  Charlotte North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease and Public Health Sciences Divisions Fred Hutchinson Cancer Center  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"B. Gilbert","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease and Public Health Sciences Divisions Fred Hutchinson Cancer Center  Seattle Washington USA"},{"name":"Department of Biostatistics University of Washington  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,3,12]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2034577"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2113017"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.27124"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2102214"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2117608"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2116185"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.2307\/2533835"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1003973"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1505819"},{"issue":"36","key":"e_1_2_12_11_1","first-page":"E8378","article-title":"Viral Genetic Diversity and Protective Efficacy of a Tetravalent Dengue Vaccine in Two Phase 3 Trials","volume":"115","author":"Michal J.","year":"2018","journal-title":"National Academy of Sciences of the United States of America"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009406"},{"issue":"1","key":"e_1_2_12_13_1","first-page":"1","article-title":"Multiple Approaches for Massively Parallel Sequencing of SARS\u2010CoV\u20102 Genomes Directly From Clinical Samples","volume":"12","author":"Minfeng X.","year":"2020","journal-title":"Genome Medicine"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01679-5"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/82.4.821"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0006-341X.2001.01191.x"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/92.4.875"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1994.10476818"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jspi.2012.02.037"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0258(20001130)19:22<3065::AID-SIM600>3.0.CO;2-D"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1214\/aos\/1031594730"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1952.10483446"},{"key":"e_1_2_12_23_1","first-page":"221","volume-title":"Proceedings of the 5th Berkeley Symposium on Mathematical Statistics and Probability","author":"Huber P. 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