Immortal Time Bias in Observational Studies of Time-to-Event Outcomes: Assessing Effects of Postmastectomy Radiation Therapy Using the National Cancer Database
Immortal Time Bias in Observational Studies of Time-to-Event Outcomes: Assessing Effects of Postmastectomy Radiation Therapy Using the National Cancer Database
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DOI：
10.1177/1073274818789355
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发表时间：
2018-07-18
期刊：
影响因子：
2.6
通讯作者：
Mazumdar, Madhu
中科院分区：
文献类型：
--
作者：
Agarwal, Parul;Moshier, Erin;Mazumdar, Madhu
本研究的目的是利用肿瘤学结果数据库来说明不朽时间偏差（ITB）的影响，并通过模拟来量化不同分析技术使用时不朽时间偏差的大小和方向。从国家癌症数据库（2004-2008）中收集了11626名接受新辅助化疗和淋巴结病理阳性的乳房切除术的妇女。使用标准Cox回归、时间相关（TD）和里程碑模型来比较接受或未接受乳房切除术后放射治疗（PMRT）的患者的总生存率。模拟研究表明，减少ITB影响的方法表明，在基于危害的分析中，应将辐射暴露作为变量包括在内。比较接受和未接受PMRT患者总生存率的标准Cox回归模型显示，PMRT治疗效果显著（风险比[HR]: 0.93, 95%可信区间[CI]: 0.88-0.99）。时间依赖法和里程碑法估计无治疗效果，HR分别为0.97,95% CI为0.92 ~ 1.03，HR为0.98,95% CI为0.92 ~ 1.04。在我们的模拟研究中，标准Cox回归模型在没有效果的情况下显著高估了治疗效果。TD模型的估计最接近真实的治疗效果。地标模型结果高度依赖于地标时间。在检查接受PMRT与生存之间的关系时，考虑到ITB的适当统计方法对于最大限度地减少偏差至关重要。
The objectives of this study are to illustrate the effects of immortal time bias (ITB) using an oncology outcomes database and quantify through simulations the magnitude and direction of ITB when different analytical techniques are used. A cohort of 11 626 women who received neoadjuvant chemotherapy and underwent mastectomy with pathologically positive lymph nodes were accrued from the National Cancer Database (2004-2008). Standard Cox regression, time-dependent (TD), and landmark models were used to compare overall survival in patients who did or did not receive postmastectomy radiation therapy (PMRT). Simulation studies showing ways to reduce the effect of ITB indicate that TD exposures should be included as variables in hazard-based analyses. Standard Cox regression models comparing overall survival in patients who did and did not receive PMRT showed a significant treatment effect (hazard ratio [HR]: 0.93, 95% confidence interval [CI]: 0.88-0.99). Time-dependent and landmark methods estimated no treatment effect with HR: 0.97, 95% CI: 0.92 to 1.03 and HR: 0.98, 95% CI, 0.92 to 1.04, respectively. In our simulation studies, the standard Cox regression model significantly overestimated treatment effects when no effect was present. Estimates of TD models were closest to the true treatment effect. Landmark model results were highly dependent on landmark timing. Appropriate statistical approaches that account for ITB are critical to minimize bias when examining relationships between receipt of PMRT and survival.