{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T21:59:54Z","timestamp":1790200794960,"version":"4.1.0"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"2","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Determining whether screening with multicancer detection (MCD) tests saves lives requires randomized controlled trials (RCTs). To inform RCT design, we estimated cancer-mortality outcomes from hypothetical MCD RCTs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We used the Hu-Zelen model, previously used to plan the National Lung Screening Trial (NLST), to estimate mortality reductions, sample size, and power for 9 cancers for different RCT design parameters and MCD test parameters.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Our base-case RCT with 5 yearly screens and 100\u00a0000 people ages 60-74 in each arm, who also undergo standard-of-care screens, has 87%-89% power to detect a 9%-10% mortality reduction (Number Needed to Screen [NNS]\u2009=\u2009578-724) over 7-9\u2009years. The majority of prevented deaths were from lung cancers (base-case [64%-66%] and all sensitivity analyses), 8%-10% from colorectal cancer, and 26% from the other 7 cancers, mostly from stomach or ovary or esophagus (due to excellent stage 1 survival) and less from liver or pancreas (poor stage 1 survival) or head and neck or lymphoma (excellent stage 4 survival). There was limited power for mortality reductions at most individual cancer sites. Base-case findings were sensitive to test sensitivity, stage shifts, and mean sojourn times in the preclinical state (especially for lung cancer), but 90% power could be recovered by recruiting a substantially higher risk population.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Large-scale MCD RCTs would have 89% power to detect an approximate 10% cancer mortality reduction over a relatively short 7-9 year timeframe from trial entry. The estimated NNS for MCD RCTs compares favorably with mammographic screening. Most prevented cancer deaths in a well-powered MCD RCT would likely be from lung cancer. Non-lung and non-colorectal cancer sites could be a meaningful proportion of prevented cancer deaths, but power is insufficient to isolate non-lung-cancer mortality reductions.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jnci\/djae247","type":"journal-article","created":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T17:36:34Z","timestamp":1728495394000},"page":"303-311","source":"Crossref","is-referenced-by-count":8,"title":["Design of randomized controlled trials to estimate cancer-mortality reductions from multicancer detection screening"],"prefix":"10.1093","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-6954-6111","authenticated-orcid":false,"given":"Ping","family":"Hu","sequence":"first","affiliation":[{"name":"Division of Cancer Prevention, Department of Health and Human Services, National Cancer Institute, National Institutes of Health , Bethesda, 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