Background The NHS-Galleri trial has demonstrated feasibility for multi-cancer screening trial design where all participants provide a ‘sample’ for screening, but only samples from the intervention arm are tested and acted upon during the trial. We assess efficiency of analysis methods when the control arm may be retrospectively tested at time of analysis. Methods Analyses considered are: (1, traditional) by randomised allocation with all events included; (2, ‘intended-effect’) nested in those who tested positive in both arms and all events therein; and (3, targeted) by randomised allocation but with endpoint ‘test-positive event’. They are compared using approximate statistical methods and scenario analysis. Results Provided the number who die from cancer after a test-positive sample is a small fraction of the total number who die from cancer, intended-effect and targeted analyses require a much smaller sample size to evaluate cancer-specific mortality than the traditional approach. Intended-effect analysis has a smaller sample size requirement than targeted analysis. This gain is only substantial when the risk of cancer death in test positives is high. Conclusion Intended-effect or targeted analysis will substantially reduce the sample size needed to evaluate cancer-specific mortality in blood-based screening trials. Targeted analysis requires many fewer retrospective tests and avoids potential effects of needing to inform those whose stored samples test positive. Trialists should consider the trade-off of costs between sample size and retrospective testing requirements when choosing the analysis.

中文翻译：

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更高效的小型多癌种筛查试验


背景 NHS-Galleri 试验证明了多癌症筛查试验设计的可行性，其中所有参与者都提供“样本”进行筛查，但在试验期间仅对来自干预组的样本进行测试和采取行动。当对照组可以在分析时进行回顾性测试时，我们会评估分析方法的效率。方法 考虑的分析是：（1，传统）随机分配，包括所有事件;（2， '预期效应'） 嵌套在双臂及其所有事件检测呈阳性的人中;（3 个，靶向）通过随机分配，但终点为“检测阳性事件”。使用近似统计方法和情景分析对它们进行比较。结果 如果检测阳性样本后死于癌症的人数占死于癌症的总人数的一小部分，则与传统方法相比，预期效应和靶向分析需要更小的样本量来评估癌症特异性死亡率。预期效应分析的样本量要求比目标分析小。只有当检测阳性者死亡癌症的风险很高时，这种收益才是可观的。结论 预期效应或靶向分析将大大减少在基于血液的筛查试验中评估癌症特异性死亡率所需的样本量。靶向分析需要的回顾性测试要少得多，并且避免了需要通知储存样本检测呈阳性的人的潜在影响。试验者在选择分析时应考虑样本量和回顾性检验要求之间的成本权衡。