{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:10:53Z","timestamp":1753870253597,"version":"3.41.2"},"reference-count":35,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T00:00:00Z","timestamp":1741132800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"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:sec><jats:title>Introduction<\/jats:title><jats:p>In causal inference with time\u2010dependent confounding between an exposure and an outcome, the repeated nature of measures is likely to lead to intra\u2010patient correlation and introduces bias in the estimation of the causal effect, even in the absence of unmeasured confounders.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>We evaluated the impact of intra\u2010patient correlation on causal effect estimation with g\u2010computation, inverse probability weighting (IPW) and longitudinal targeted maximum likelihood estimator (LTMLE), and compared two ways of accounting for it, using a fixed\u2010effects or a mixed\u2010effects approach. We conducted a simulation analysis under different scenarios for numerous time points and a real\u2010life analysis to investigate the causal effect of pregnancy on neurological disability in multiple sclerosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In simulation analyses, the presence of intra\u2010patient correlation led to bias in the causal effect estimation with g\u2010computation, IPW, and LTMLE when this was not accounted for; the bias was smaller for LTMLE. Taking into account intra\u2010patient correlation with fixed\u2010effects and mixed\u2010effects approaches reduced the bias in g\u2010computation, with lower standard errors for the mixed\u2010effects approach. Regarding IPW, the fixed\u2010effects approach suffered from weight stability issues when the number of time points increased, and the mixed\u2010effects approach provided inconsistent estimates of the intra\u2010patient correlation in the exposure model. Application to real\u2010life data yielded results consistent with the simulation study, highlighting the importance of accounting for intra\u2010patient correlation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>When analyzing longitudinal data in the presence of time\u2010dependent confounding using g\u2010methods, intra\u2010patient correlation due to repeated measurements of exposure and outcome should be accounted for in the causal reasoning.<\/jats:p><\/jats:sec>","DOI":"10.1002\/sim.70037","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T15:39:15Z","timestamp":1741707555000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Causal Inference in Presence of Intra\u2010Patient Correlation due to Repeated Measurements of Exposure and Outcome in Longitudinal Settings"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9118-0849","authenticated-orcid":false,"given":"Antoine","family":"Gavoille","sequence":"first","affiliation":[{"name":"Universit\u00e9 de Lyon, Universit\u00e9 Lyon 1, CNRS, Laboratoire de Biom\u00e9trie et Biologie \u00c9volutive UMR 5558  Villeurbanne France"},{"name":"Service de Biostatistique\u2010Bioinformatique, Hospices Civils de Lyon  Lyon France"},{"name":"Hospices Civils de Lyon, Service de Neurologie, Scl\u00e9rose en Plaques, Pathologies de la My\u00e9line et Neuro\u2010Inflammation  Bron France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabien","family":"Rollot","sequence":"additional","affiliation":[{"name":"Observatoire Fran\u00e7ais de la Scl\u00e9rose en Plaques (OFSEP), H\u00f4pital Neurologique Pierre\u2010Wertheimer  Bron France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Romain","family":"Casey","sequence":"additional","affiliation":[{"name":"Observatoire Fran\u00e7ais de la Scl\u00e9rose en Plaques (OFSEP), H\u00f4pital Neurologique Pierre\u2010Wertheimer  Bron France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Vukusic","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon, Service de Neurologie, Scl\u00e9rose en Plaques, Pathologies de la My\u00e9line et Neuro\u2010Inflammation  Bron France"},{"name":"Observatoire Fran\u00e7ais de la Scl\u00e9rose en Plaques (OFSEP), H\u00f4pital Neurologique Pierre\u2010Wertheimer  Bron France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muriel","family":"Rabilloud","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lyon, Universit\u00e9 Lyon 1, CNRS, Laboratoire de Biom\u00e9trie et Biologie \u00c9volutive UMR 5558  Villeurbanne France"},{"name":"Service de Biostatistique\u2010Bioinformatique, Hospices Civils de Lyon  Lyon France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabien","family":"Subtil","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lyon, Universit\u00e9 Lyon 1, CNRS, Laboratoire de Biom\u00e9trie et Biologie \u00c9volutive UMR 5558  Villeurbanne France"},{"name":"Service de Biostatistique\u2010Bioinformatique, Hospices Civils de Lyon  Lyon France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,3,5]]},"reference":[{"volume-title":"Causal Inference: What if","year":"2020","author":"Hern\u00e1n M.","key":"e_1_2_13_2_1"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001648\u2010200009000\u201000011"},{"key":"e_1_2_13_4_1","first-page":"30","volume-title":"Statistical Models in Epidemiology, the Environment, and Clinical Trials","author":"Robins J. M.","year":"1999"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.5686"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/jech.2004.029496"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0270\u20100255(86)90088\u20106"},{"issue":"1","key":"e_1_2_13_8_1","first-page":"41","article-title":"Targeted Minimum Loss Based Estimation of Causal Effects of Multiple Time Point Interventions","volume":"8","author":"Laan M. J.","year":"2012","journal-title":"International Journal of Biostatistics"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/9781119513469"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.7567"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/kxv029"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/anzs.12422"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurol.2015.10.006"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.33.11.1444"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp\u20102012\u2010302848"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2008.163816"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000007178"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2019.01.003"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1999.10474168"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/1536867X1201100401"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyp192"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00127-016-1281-9"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwn164"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1177\/0962280210386207"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v081.i01"},{"volume-title":"R: A Language and Environment for Statistical Computing","year":"2020","key":"e_1_2_13_26_1"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v081.i02"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.8340"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.8300"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.8710"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.9727"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1515\/ijb\u20102017\u20100054"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000206774"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1144"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1177\/0962280219900362"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annepidem.2019.04.008"}],"container-title":["Statistics in Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/sim.70037","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T14:27:24Z","timestamp":1749047244000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/sim.70037"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,5]]},"references-count":35,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,3,15]]}},"alternative-id":["10.1002\/sim.70037"],"URL":"https:\/\/doi.org\/10.1002\/sim.70037","archive":["Portico"],"relation":{},"ISSN":["0277-6715","1097-0258"],"issn-type":[{"type":"print","value":"0277-6715"},{"type":"electronic","value":"1097-0258"}],"subject":[],"published":{"date-parts":[[2025,3,5]]},"assertion":[{"value":"2024-04-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70037"}}