{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:09:40Z","timestamp":1788826180016,"version":"build-2803163510"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"vor","delay-in-days":14,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015803","name":"BC Cancer Foundation","doi-asserted-by":"publisher","award":["F25-02938"],"award-info":[{"award-number":["F25-02938"]}],"id":[{"id":"10.13039\/501100015803","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Surrogate endpoints are increasingly used as the basis of cancer drug approvals. A strong association between treatment effects on the surrogate and true endpoint is essential for their validation as reliable endpoints. We assess the current evidence of trial-level surrogacy for colorectal cancer (CRC) endpoints through a novel framework.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We developed a framework to grade the quality of oncology surrogate endpoints in 7 domains of the surrogate relationship: data source quality (A-B); disease setting homogeneity (0-3); uniformness of surrogate and true endpoint definitions (0-3); number of trials evaluated (0-4); and individual- (0-2) and trial-level associations (0-8). We screened PubMed using keywords and medical subject headings terms for meta-analyses published before July 6, 2024, validating surrogate endpoint associations across CRC trials. Two reviewers blindly assessed each article before reaching a consensus score. The main outcomes were framework-derived evidence scores and reported trial-level associations (R2) with overall survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 18 articles were identified, containing 39 evaluations of 12 unique surrogate endpoints for overall survival. Evidence scores ranged from B6 to A23. Only disease-free survival consistently demonstrated high-quality evidence of trial-level surrogacy (\u2265A18, median R2 = 0.92). Progression-free survival and objective response rate were low-quality surrogates in metastatic CRC (progression-free survival: B6-A15, median R2 = 0.55; objective response rate: B6-A13, median R2 = 0.33). Other evaluated endpoints were demonstrated to be\u00a0unreliable surrogates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Disease-free survival shows high-quality surrogacy in stage II-III colon cancer. Endpoints identified in the metastatic setting demonstrate inconsistent surrogacy evidence. Reassessment and identification of new endpoints are warranted, particularly with immunotherapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jnci\/djag088","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T12:42:29Z","timestamp":1773924149000},"page":"1618-1627","source":"Crossref","is-referenced-by-count":1,"title":["A framework to evaluate surrogate endpoints at the trial level: analysis in colorectal cancer"],"prefix":"10.1093","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4337-7076","authenticated-orcid":false,"given":"Brendan J","family":"Chia","sequence":"first","affiliation":[{"name":"Medical Oncology, BC Cancer\u2014Vancouver Cancer Centre , Vancouver, BC,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Allegra","sequence":"additional","affiliation":[{"name":"Hematology and Oncology, University of Florida College of Medicine , Gainesville, 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