Randomized trials of the efficacy of multi-cancer early detection, by means of measurement of cell-free DNA and/or protein biomarkers in peripheral blood specimens, will attempt to document a difference in cancer mortality between persons assigned to intervention and control arms. Their ability to do so is limited by the relatively low rate of death from individual forms of cancer, the relatively low sensitivity of the tests currently being used, and the use of other cancer screening modalities among trial participants. However, if those same blood specimens also could be obtained from control arm participants in a given trial and then tested for the same markers, with results not known (or not made available) until the conclusion of follow-up for cancer mortality, it would be possible to compare mortality from given forms of cancer between test-positive individuals whose results were known and not known during the course of the trial. Such an analysis addresses the impact of a stimulus to offer targeted diagnostic testing, potentially leading to early treatment, against cancer mortality. Among persons who screen as positive, it should provide a relatively more sensitive means of gauging a possible mortality benefit resulting from multi-cancer screening.

中文翻译：

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多种癌症筛查测试的随机试验：增强识别真正死亡率益处的能力

通过测量外周血样本中的无细胞 DNA 和/或蛋白质生物标志物，对多种癌症早期检测的功效进行随机试验，将试图记录分配到干预组和对照组的人之间癌症死亡率的差异。他们这样做的能力受到个别癌症死亡率相对较低、目前使用的测试敏感性相对较低以及试验参与者使用其他癌症筛查方式的限制。然而，如果也可以从给定试验中的对照组参与者获得相同的血液样本，然后测试相同的标记物，并且在癌症死亡率随访结束之前结果未知（或无法提供），那么可以比较在试验过程中结果已知和未知的测试阳性个体之间特定形式癌症的死亡率。这样的分析解决了刺激措施提供有针对性的诊断测试的影响，可能导致早期治疗，降低癌症死亡率。对于筛查结果呈阳性的人来说，它应该提供一种相对更敏感的方法来衡量多种癌症筛查可能带来的死亡率益处。