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Panels expand treatment de\u2010escalation by expanding\n                      <jats:italic>RAS<\/jats:italic>\n                      testing for more precise targeting of anti\u2010\n                      <jats:italic>EGFR<\/jats:italic>\n                      therapies. Reimbursement of panels remains unequal across healthcare systems given uncertain clinical and economic impacts. Our quasi\u2010experimental study design followed the target trial emulation approach, emulating random treatment assignment with two different methods to examine the sensitivity of estimates: inverse probability of treatment weighting estimated with super learning (SL\u2010IPTW) and 1:1 genetic algorithm\u2010based matching, a machine learning approach. We then estimated mean three\u2010year survival time and costs (public healthcare payer perspective; 2021CAD) and calculated the incremental net monetary benefit (INMB) for life\u2010years gained (LYG) at $50,000\/LYG using weighted linear regression and nonparametric bootstrapping, also accounting for inverse probability of censoring weights. Our sensitivity analysis estimated LYG using targeted minimum\u2010based loss estimation (TMLE), a doubly robust approach that also uses super learning.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data Sources and Analytical Sample<\/jats:title>\n                    <jats:p>Patient\u2010level linked administrative health databases capturing cancer and non\u2010cancer care for all BC adults with a metastatic colorectal cancer between 2016 and 2019.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Principal Findings<\/jats:title>\n                    <jats:p>Our study included 892 patients (84.3%) receiving multi\u2010gene panels and 166 (15.7%) receiving single\u2010gene testing. INMB estimates were similar for SL\u2010IPTW ($20,397; 95% CI: $9317, $34,862) and matching ($19,569; 95% CI: $8509, $31,447), with 99.3% and 98.8% probabilities, respectively, of panels being cost\u2010effective. We found statistically significant survival benefits with LYG of 0.31 (SL\u2010IPTW; 95% CI: 0.04, 0.54), 0.25 (matching; 95% CI: 0.03, 0.47) and 0.19 (TMLE; 95% CI: 0.02, 0.37).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Survival impacts were robust to super learning approaches. Real\u2010world evidence demonstrates that reimbursing multi\u2010gene sequencing for more precise targeting of mCRC treatments provides value for healthcare systems and clinically important benefits to patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1475-6773.70009","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T16:33:43Z","timestamp":1755102823000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Determining the Survival Impact and Cost\u2010Effectiveness of Multi\u2010Gene Panel Sequencing in Metastatic Colorectal Cancer With Super Learning Approaches"],"prefix":"10.1111","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6590-8728","authenticated-orcid":false,"given":"Emanuel","family":"Krebs","sequence":"first","affiliation":[{"name":"Regulatory Science Lab BC Cancer Research Institute  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3072-5657","authenticated-orcid":false,"given":"Deirdre","family":"Weymann","sequence":"additional","affiliation":[{"name":"Regulatory Science Lab BC Cancer Research Institute  Vancouver British Columbia Canada"},{"name":"Faculty of Health Sciences Simon Fraser University  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard J.","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology BC Cancer  Vancouver British Columbia Canada"},{"name":"Department of Medicine Faculty of Medicine, University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Yip","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Laboratory Medicine Faculty of Medicine, University of British Columbia  Vancouver British Columbia Canada"},{"name":"Cancer Genetics &amp; Genomics Laboratory BC Cancer  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean A.","family":"Regier","sequence":"additional","affiliation":[{"name":"Regulatory Science Lab BC Cancer Research Institute  Vancouver British Columbia Canada"},{"name":"School of Population and Public Health, Faculty of Medicine University of British Columbia; Vancouver  British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,13]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21772"},{"key":"e_1_2_10_3_1","unstructured":"Centers for Disease Control and Prevention \u201cCancer of the Colon and Rectum \u2010 Cancer Stat Facts \u201dSEER (2024) https:\/\/seer.cancer.gov\/statfacts\/html\/colorect.html."},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.01690"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/17588359221111705"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdu378"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2022.10.003"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jval.2019.07.009"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcpo.2017.03.008"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcpo.2024.100496"},{"key":"e_1_2_10_11_1","unstructured":"BC Cancer Foundation \u201cNew Genetic Tests Become Standard of Cancer Care in BC \u201d(2016) https:\/\/bccancerfoundation.com\/news\u2010and\u2010media\/blog\/new\u2010genetic\u2010tests\u2010become\u2010standard\u2010cancer\u2010care\u2010bc\/."},{"key":"e_1_2_10_12_1","unstructured":"Cancer Genetics and Genomics Laboratory \u201cOncopanel \u201d(2023) http:\/\/cancergeneticslab.ca\/genes\/oncopanel\/."},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwv254"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010019\u20100597\u2010x"},{"key":"e_1_2_10_15_1","unstructured":"\u201cHealth Sector Information Analysis and Reporting (HSIAR) Division \u201dB.C. 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