There is growing interest in multicancer detection (MCD) tests, which identify molecular signals in the blood indicating a potential preclinical cancer. A key stage in evaluating MCD tests is a prediagnostic performance study, in which investigators store specimens from asymptomatic persons and later test stored specimens from cancer cases and a random sample of controls to determine predictive performance. Performance metrics include cancer-specific true and false positive rates and a cancer-specific positive predictive value, with the latter compared to a decision-analytic threshold. The sample size tradeoff method, which trades imprecise targeting of the true positive rate for precise targeting of a zero false positive rate can substantially reduce sample size while increasing the lower bound of positive predictive value. For a 1-year follow-up, with ovarian cancer as the rarest cancer considered, the sample size tradeoff method yields a sample size of 163,000 compared with a sample size of 720,000 based on standard calculations. These design and analysis recommendations should be considered in planning a specimen repository and in the prediagnostic evaluation of MCD tests.

中文翻译：

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多种癌症检测测试的诊断前评估：设计和分析注意事项

人们对多癌检测（MCD）测试越来越感兴趣，这种测试可以识别血液中指示潜在临床前癌症的分子信号。评估 MCD 测试的一个关键阶段是诊断前性能研究，其中研究人员存储无症状人员的样本，然后测试存储的癌症病例样本和随机对照样本，以确定预测性能。性能指标包括癌症特异性真阳性率和假阳性率以及癌症特异性阳性预测值，后者与决策分析阈值进行比较。样本量权衡方法用不精确的真阳性率目标换取精确的零假阳性率目标，可以大幅减少样本量，同时提高阳性预测值的下限。对于为期 1 年的随访，考虑到卵巢癌是最罕见的癌症，样本量权衡方法得出的样本量为 163,000，而根据标准计算得出的样本量为 720,000。在规划样本库和 MCD 测试的诊断前评估时应考虑这些设计和分析建议。