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Parameters in the meta\u2010analytic model are used to assess the quality of the proposed surrogate. Recently, meta\u2010analytic models have been employed to evaluate whether late\u2010stage cancer incidence can serve as a surrogate for cancer mortality in cancer screening trials. A major challenge in meta\u2010analytic models is that uncertainty of trial\u2010level estimates affects the evaluation of surrogacy, since each trial provides only estimates of the primary and surrogate endpoints rather than their true parameter values. In this work, we show via simulation and theory that trial\u2010level estimate uncertainty may bias the results of meta\u2010analytic models toward positive findings of the quality of the surrogate. We focus on cancer screening trials and the late\u2010stage incidence surrogate. We reassess correlations between primary and surrogate endpoints in Ovarian cancer screening trials. Our findings indicate that completed trials provide limited information regarding quality of the late\u2010stage incidence surrogate. These results support restricting meta\u2010analytic regression usage to settings where trial\u2010level estimate uncertainty is incorporated into the model.<\/jats:p>","DOI":"10.1002\/sim.70731","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T01:17:32Z","timestamp":1788830252000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bias in Meta\u2010Analytic Modeling of Surrogate Endpoints in Cancer Screening Trials"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5853-5938","authenticated-orcid":false,"given":"James P.","family":"Long","sequence":"first","affiliation":[{"name":"University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhishikta","family":"Roy","sequence":"additional","affiliation":[{"name":"University of Texas School of Public Health  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ehsan","family":"Irajizad","sequence":"additional","affiliation":[{"name":"University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim\u2010Anh","family":"Do","sequence":"additional","affiliation":[{"name":"University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Shen","sequence":"additional","affiliation":[{"name":"University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"e_1_2_12_2_1","unstructured":"USPSTF \u201cU.S. Preventive Services Task Force \u201d(2024) https:\/\/www.uspreventiveservicestaskforce.org. accessed: July 11 2024."},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.01460"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2021.05.806"},{"key":"e_1_2_12_5_1","unstructured":"NCI \u201cCancer Screening Research Network (CSRN) \u201d(2024) https:\/\/prevention.cancer.gov\/major\u2010programs\/cancer\u2010screening\u2010research\u2010network\u2010csrn. accessed: July 11 2024."},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djae088"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djac218"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1102873"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/jncimono\/1997.22.27"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.22.7041"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/09691413241256744"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/09691413241228041"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.5814"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14194818"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-22-0024"},{"key":"e_1_2_12_16_1","unstructured":"M. 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