School of Medicine, Oregon Health & Science University, Portland, OR, USA.
Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA.
Eur J Cancer. 2020 Dec;141:152-161. doi: 10.1016/j.ejca.2020.09.031. Epub 2020 Nov 5.
Kaplan-Meier survival analysis, the cornerstone of evaluating efficacy of oncology drugs in randomised controlled trials (RCTs), assumes censored patients are neither healthier nor sicker than those followed. We sought to examine whether censoring patterns differ between the control and experimental arms in one oncology journal that mandates the reporting of the number of patients censored.
In this retrospective review, proportion of censoring and study design data were gathered from RCTs published in The Lancet Oncology that reported Kaplan-Meier curves between May 2018 and August 2019. Differential censoring rates were analysed at the 1st, 3rd, 6th, and overall time points in each study. Analysis was stratified by curves reporting progression-free survival (PFS) or overall survival (OS) end-points.
Of the 160 articles reviewed, 29 studies with 51 Kaplan-Meier curves were eligible. In both OS (N = 25) and PFS curves (N = 26), the absolute weighted difference in censoring between the control and experimental arms was initially positive, indicating more censoring in the control arm (first time point OS: 0.32%; PFS: 2.00%). The absolute difference then became negative, indicating more censoring in the experimental arm as time progressed (end-of-study OS: -7.54%; PFS: -9.09%).
Differences in censoring between control and experimental arms of cancer RCTs suggest that there could be systematic bias present at various study time points that may influence key results. Further investigation is needed, as possible reasons include study assignment disappointment, inappropriate follow-up length, lack of efficacy, or intolerable toxicity, each predominant at specific time points after randomisation.
Kaplan-Meier 生存分析是评估随机对照试验（RCT）中肿瘤药物疗效的基石，它假设删失患者不比随访患者更健康或更不健康。我们试图研究在一家强制报告删失患者数量的肿瘤学杂志中，对照和实验组的删失模式是否存在差异。
在这项回顾性研究中，我们从 2018 年 5 月至 2019 年 8 月发表在《柳叶刀肿瘤学》上的报告 Kaplan-Meier 曲线的 RCT 中收集了比例删失和研究设计数据。在每个研究的第 1、3、6 和总时间点分析了差异删失率。分析按报告无进展生存期（PFS）或总生存期（OS）终点的曲线进行分层。
在审查的 160 篇文章中，有 29 项研究有 51 个 Kaplan-Meier 曲线符合条件。在 OS（N=25）和 PFS 曲线（N=26）中，对照组和实验组之间的绝对加权删失差异最初为正，表明对照组的删失更多（第 1 个时间点 OS：0.32%；PFS：2.00%）。然后，绝对差异变为负，表明随着时间的推移实验组的删失更多（研究结束时 OS：-7.54%；PFS：-9.09%）。
癌症 RCT 对照组和实验组之间的删失差异表明，在各个研究时间点可能存在系统性偏倚，这可能影响关键结果。需要进一步调查，因为可能的原因包括研究分配失望、随访时间不当、缺乏疗效或不可耐受的毒性，每种原因在随机分组后特定时间点都占主导地位。
