{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T18:41:56Z","timestamp":1788028916848,"version":"build-2784847793"},"reference-count":26,"publisher":"Wiley","issue":"10-12","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K17301"],"award-info":[{"award-number":["22K17301"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006093","name":"Patient-Centered Outcomes Research Institute","doi-asserted-by":"publisher","award":["ME\u20102024C3\u201043044"],"award-info":[{"award-number":["ME\u20102024C3\u201043044"]}],"id":[{"id":"10.13039\/100006093","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":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>In the presence of competing events, many investigators are interested in a direct treatment effect on the event of interest that does not capture treatment effects on competing events. Classical survival analysis methods that treat competing events like censoring events, at best, target a controlled direct effect: the effect of the treatment under a difficult to imagine and typically clinically irrelevant scenario where competing events are somehow eliminated. A separable direct effect, quantifying the effect of a future modified version of the treatment, is an alternative direct effect notion that may better align with an investigator's underlying causal question. In this paper, we provide insights into the implications of naively applying an estimator constructed for a controlled direct effect (i.e., \u201ccensoring by competing events\u201d) when the actual causal effect of interest is a separable direct effect. We illustrate the degree to which controlled and separable direct effects may take different values, possibly even different signs, and the degree to which these two different effects may be differentially impacted by violation and\/or near violation of their respective identifying conditions under a range of data generating scenarios. Finally, we provide an empirical comparison of inverse probability of censoring weighting to an alternative weighted estimator specifically structured for a separable effect using data from a randomized trial of estrogen therapy and prostate cancer mortality.<\/jats:p>","DOI":"10.1002\/sim.70535","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T22:52:19Z","timestamp":1777071139000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Illustrating Implications of Misaligned Causal Questions and Statistics in Settings With Competing Events and Interest in Treatment Mechanisms"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3859-2756","authenticated-orcid":false,"given":"Takuya","family":"Kawahara","sequence":"first","affiliation":[{"name":"Department of Population Medicine Harvard Medical School and Harvard Pilgrim Health Care Institute  Boston Massachusetts USA"},{"name":"Clinical Research Promotion Center The University of Tokyo Hospital  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7281-3516","authenticated-orcid":false,"given":"Sean","family":"McGrath","sequence":"additional","affiliation":[{"name":"Department of Population Medicine Harvard Medical School and Harvard Pilgrim Health Care Institute  Boston Massachusetts USA"},{"name":"Department of Biostatistics Yale School of Public Health  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica G.","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Population Medicine Harvard Medical School and Harvard Pilgrim Health Care Institute  Boston Massachusetts USA"},{"name":"Department of Epidemiology Harvard T.H. Chan School of Public Health  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001648-199203000-00013"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.8471"},{"issue":"4","key":"e_1_2_11_4_1","first-page":"477","article-title":"The Choice of Treatment for Cancer Patients Based on Covariate Information","volume":"67","author":"Byar D.","year":"1980","journal-title":"Bulletin du Cancer"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41391-018-0081-6"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10985-018-9449-0"},{"key":"e_1_2_11_7_1","first-page":"103","article-title":"Alternative Graphical Causal Models and the Identification of Direct Effects","author":"Robins J. M.","year":"2010","journal-title":"Causality and Psychopathology: Finding the Determinants of Disorders and Their Cures"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1145\/3501714.3501754"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10985-021-09530-8"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.2020.1765783"},{"key":"e_1_2_11_11_1","volume-title":"Data Analysis With Competing Risks and Intermediate States","author":"Geskus R. B.","year":"2016"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.70009"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/biom.13523"},{"key":"e_1_2_11_14_1","first-page":"1","article-title":"Single World Intervention Graphs (SWIGs): A Unification of the Counterfactual and Graphical Approaches to Causality","volume":"128","author":"Richardson T. S.","year":"2013","journal-title":"Center for the Statistics and the Social Sciences, University of Washington Series. Working Paper"},{"key":"e_1_2_11_15_1","volume-title":"Causal Inference: What if","author":"Hern\u00e1n M. A.","year":"2020"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0000000000001339"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.2022.2071276"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/0962280210386207"},{"key":"e_1_2_11_19_1","unstructured":"A. L.Sarvet M. J.Stensrud andL.Wen \u201cInterpretational Errors in Statistical Causal Inference \u201d(2023) arXiv:2312.07610."},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0000000000001704"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.patter.2020.100008"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/ectj.12097"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-21700-0"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-65304-4"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.2021.1955691"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.2017.1422737"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1515\/em-2012-0001"}],"container-title":["Statistics in Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/sim.70535","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/sim.70535","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/sim.70535","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T20:11:04Z","timestamp":1786479064000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/sim.70535"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,24]]},"references-count":26,"journal-issue":{"issue":"10-12","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/sim.70535"],"URL":"https:\/\/doi.org\/10.1002\/sim.70535","archive":["Portico"],"relation":{},"ISSN":["0277-6715","1097-0258"],"issn-type":[{"value":"0277-6715","type":"print"},{"value":"1097-0258","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,24]]},"assertion":[{"value":"2025-11-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70535"}}