Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, Tennessee.
Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, Tennessee.
Int J Radiat Oncol Biol Phys. 2020 Jan 1;106(1):5-12. doi: 10.1016/j.ijrobp.2019.07.056. Epub 2019 Aug 9.
In studies evaluating the benefit of adjuvant therapies, immortal time bias (ITB) can affect the results by incorrectly reporting a survival advantage. It does so by including all deceased patients who may have been planned to receive adjuvant therapy within the observation cohort. Given the increase in National Cancer Database (NCDB) analyses evaluating postoperative radiation therapy (PORT) as an adjuvant therapy, we sought to examine how often such studies accounted and adjusted for ITB.
A systematic review was undertaken to search MEDLINE and EMBASE from January 2014 until May 2019 for NCDB studies evaluating PORT. After appropriate exclusion criteria were applied, 60 peer-reviewed manuscripts in which PORT was compared with postoperative observation or maintenance therapy were reviewed. The manuscripts were reviewed to evaluate whether ITB was accounted for, the method with which it was adjusted for, impact factor, year of publication, and whether PORT was beneficial.
Of the 60 publications reviewed, 23 studies (38.3%) did not include an adjustment for ITB. Most studies that did adjust for ITB employed a single landmark (LM) time (n = 31), 4 used a sequential landmark analyses, and 2 used a time-dependent Cox model. In 23 of 31 studies (74.2%) that did adjust for ITB via a single LM time, the rationale behind why the specified LM time was chosen was not clearly explained. There was no relationship between adjusting for ITB and year of publication (P = .074) or whether the study was published in a high-impact journal (P = .55).
Studies assessing adjuvant radiation therapy by analyzing the NCDB are susceptible to ITB, which overestimates the effect size of adjuvant therapies and can provide misleading results. Adjusting for this bias is essential for accurate data representation and to better quantify the impact of adjuvant therapies such as PORT.
在评估辅助治疗益处的研究中， Immortal time bias（ITB）可能会通过错误报告生存优势而影响结果。它通过将所有计划接受辅助治疗的已故患者包含在观察队列中来实现这一点。鉴于越来越多的国家癌症数据库（NCDB）分析评估术后放射治疗（PORT）作为辅助治疗，我们试图研究此类研究经常如何考虑和调整 ITB。
进行了系统评价，以从 2014 年 1 月至 2019 年 5 月在 MEDLINE 和 EMBASE 中搜索评估 PORT 的 NCDB 研究。在应用适当的排除标准后，回顾了 60 篇经同行评审的手稿，其中 PORT 与术后观察或维持治疗进行了比较。审查手稿以评估是否考虑了 ITB，调整方法，影响因素，出版年份以及 PORT 是否有益。
在审查的 60 篇出版物中，有 23 项研究（38.3％）未包括对 ITB 的调整。大多数对 ITB 进行调整的研究都采用了单一的标记（LM）时间（n = 31），4 项研究采用了连续标记分析，2 项研究采用了时间依赖性 Cox 模型。在通过单一 LM 时间对 ITB 进行调整的 23 项研究中有 23 项（74.2％），未明确说明选择特定 LM 时间的依据。调整 ITB 与出版年份之间没有关系（P =.074），也与研究是否在高影响力期刊上发表无关（P =.55）。
通过分析 NCDB 评估辅助放射治疗的研究容易受到 ITB 的影响，这会高估辅助治疗的效果大小，并提供误导性结果。调整这种偏差对于准确表示数据和更好地量化 PORT 等辅助治疗的影响至关重要。
