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In this paper, we consider different estimands of the vaccine efficacy that are interpretable even when the proportional hazard assumption is not met, including estimands based on the average hazard ratio, the cumulative incidence ratio, and the restricted mean time lost ratio. Under the assumption that different estimands target relevant clinical questions, power becomes a crucial factor in choosing the preferred estimand. We focus on the power of these different estimands in vaccine efficacy trials, and we illustrate them in a human papillomavirus phase III vaccine trial. In classical settings of prophylactic vaccine efficacy trials, our results show that the average hazard ratio and cumulative incidence ratio give similar results, while the restricted mean time lost ratio is expected to be less powerful.<\/jats:p>","DOI":"10.1177\/09622802251412833","type":"journal-article","created":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T06:48:22Z","timestamp":1775198902000},"page":"962-979","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Vaccine efficacy estimands and power considerations"],"prefix":"10.1177","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4805-5118","authenticated-orcid":false,"given":"Andrea","family":"Callegaro","sequence":"first","affiliation":[{"name":"GlaxoSmithKline"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9946-0119","authenticated-orcid":false,"given":"Nathan W.","family":"Bean","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,4,2]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a009196"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/68.1.105"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/1.4.423"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.2248"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.3623"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1080\/19466315.2016.1257436"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0b013e3181c1ea43"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4274"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.55.2208"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.9651"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1214\/21-STS830"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/biom.12770"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1177\/1740774520976576"},{"key":"e_1_3_2_15_2","first-page":"20220003","article-title":"Estimation and interpretation of vaccine efficacy in COVID-19 randomized clinical trials","volume":"14","author":"Michiels H","year":"2022","unstructured":"Michiels H, Vandebosch A, Vansteelandt S. 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