Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT, USA.
Int J Radiat Oncol Biol Phys. 2012 Aug 1;83(5):1365-73. doi: 10.1016/j.ijrobp.2011.10.025. Epub 2012 Feb 16.
To evaluate the influence of immortal time bias on observational cohort studies of postoperative radiotherapy (PORT) and the effectiveness of sequential landmark analysis to account for this bias.
First, we reviewed previous studies of the Surveillance, Epidemiology, and End Results (SEER) database to determine how frequently this bias was considered. Second, we used SEER to select three tumor types (glioblastoma multiforme, Stage IA-IVM0 gastric adenocarcinoma, and Stage II-III rectal carcinoma) for which prospective trials demonstrated an improvement in survival associated with PORT. For each tumor type, we calculated conditional survivals and adjusted hazard ratios of PORT vs. postoperative observation cohorts while restricting the sample at sequential monthly landmarks.
Sixty-two percent of previous SEER publications evaluating PORT failed to use a landmark analysis. As expected, delivery of PORT for all three tumor types was associated with improved survival, with the largest associated benefit favoring PORT when all patients were included regardless of survival. Preselecting a cohort with a longer minimum survival sequentially diminished the apparent benefit of PORT.
Although the majority of previous SEER articles do not correct for it, immortal time bias leads to altered estimates of PORT effectiveness, which are very sensitive to landmark selection. We suggest the routine use of sequential landmark analysis to account for this bias.
评估观察性队列研究中永生时间偏倚对术后放疗（PORT）的影响，并评估序贯 landmark 分析对此偏倚的校正效果。
首先，我们回顾了 Surveillance、Epidemiology 和 End Results（SEER）数据库中的既往研究，以确定这种偏倚被考虑的频率。其次，我们使用 SEER 选择了三种肿瘤类型（多形性胶质母细胞瘤、IA-IVM0 期胃腺癌和 II-III 期直肠癌），前瞻性试验表明 PORT 与生存改善相关。对于每种肿瘤类型，我们计算了 PORT 与术后观察队列的条件生存率和调整后的危险比，同时在序贯每月 landmark 处限制样本。
62%的评估 PORT 的既往 SEER 出版物未能使用 landmark 分析。正如预期的那样，对于所有三种肿瘤类型，PORT 的应用都与生存改善相关，当无论生存情况如何，所有患者均纳入时，PORT 相关的获益最大。预先选择一个具有更长最小生存时间的队列，会逐渐降低 PORT 的明显获益。
尽管大多数既往 SEER 文章并未对此进行校正，但永生时间偏倚会导致 PORT 有效性的估计值发生改变，且这种改变对 landmark 的选择非常敏感。我们建议常规使用序贯 landmark 分析来校正这种偏倚。
