Baker Stuart G, Kramer Barnett S, Prorok Philip C
Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892-7354, USA.
J Med Screen. 2008;15(3):122-9. doi: 10.1258/jms.2008.007058.
Many cancer screening trials involve a screening programme of one or more screenings with follow-up after the last screening. Usually a maximum follow-up time is selected in advance. However, during the follow-up period there is an opportunity to report the results of the trial sooner than planned. Early reporting of results from a randomized screening trial is important because obtaining a valid result sooner translates into health benefits reaching the general population sooner. The health benefits are reduction in cancer deaths if screening is found to be beneficial and more screening is recommended, or avoidance of unnecessary biopsies, work-ups and morbidity if screening is not found to be beneficial and the rate of screening drops.
Our proposed method for deciding if results from a cancer screening trial should be reported earlier in the follow-up period is based on considerations involving postscreening noise. Postscreening noise (sometimes called dilution) refers to cancer deaths in the follow-up period that could not have been prevented by screening: (1) cancer deaths in the screened group that occurred after the last screening in subjects whose cancers were not detected during the screening program and (2) cancer deaths in the control group that occurred after the time of the last screening and whose cancers would not have been detected during the screening programme had they been randomized to screening (the number of which is unobserved). Because postscreening noise increases with follow-up after the last screening, we propose early reporting at the time during the follow-up period when postscreening noise first starts to overwhelm the estimated effect of screening as measured by a z-statistic. This leads to a confidence interval, adjusted for postscreening noise, that would not change substantially with additional follow-up. Details of the early reporting rule were refined by simulation, which also accounts for multiple looks.
For the re-analysis of the Health Insurance Plan trial for breast cancer screening and the Mayo Lung Project for lung cancer screening, estimates and confidence intervals for the effect of screening on cancer mortality were similar on early reporting and later.
The proposed early reporting rule for a cancer screening trial with post-screening follow-up is a promising method for making results from the trial available sooner, which translates into health benefits (reduction in cancer deaths or avoidance of unnecessary morbidity) reaching the population sooner.
许多癌症筛查试验涉及一项或多项筛查的筛查计划，并在最后一次筛查后进行随访。通常会提前选择最长随访时间。然而，在随访期间，有机会比计划更早地报告试验结果。随机筛查试验结果的早期报告很重要，因为更快获得有效结果意味着健康益处能更快惠及普通人群。如果发现筛查有益并建议增加筛查，健康益处是降低癌症死亡率；如果发现筛查无益且筛查率下降，健康益处则是避免不必要的活检、检查和发病率。
我们提出的用于判断癌症筛查试验结果是否应在随访期更早报告的方法，是基于对筛查后噪声的考虑。筛查后噪声（有时称为稀释）指随访期内无法通过筛查预防的癌症死亡：（1）筛查组中在筛查项目中未检测出癌症的受试者在最后一次筛查后发生的癌症死亡；（2）对照组中在最后一次筛查时间之后发生的癌症死亡，且如果他们被随机分配到筛查组，其癌症在筛查项目中也不会被检测出（其数量不可观察）。由于筛查后噪声会随着最后一次筛查后的随访而增加，我们建议在随访期内当筛查后噪声首次开始超过以z统计量衡量的筛查估计效果时进行早期报告。这会得出一个针对筛查后噪声进行调整的置信区间，该区间不会因额外随访而有实质性变化。早期报告规则的细节通过模拟进行了完善，模拟还考虑了多次观察。
对于乳腺癌筛查的健康保险计划试验和肺癌筛查的梅奥肺癌项目的重新分析，筛查对癌症死亡率影响的估计值和置信区间在早期报告和后期报告时相似。
对于有筛查后随访的癌症筛查试验，所提出的早期报告规则是一种有前景的方法，可使试验结果更快可用，这意味着健康益处（降低癌症死亡率或避免不必要的发病率）能更快惠及人群。
