Matsuyama Yutaka, Yamaguchi Takuhiro
Department of Biostatistics, School of Health Sciences and Nursing, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Pharm Stat. 2008 Jul-Sep;7(3):202-14. doi: 10.1002/pst.290.
In medical studies, there is interest in inferring the marginal distribution of a survival time subject to competing risks. The Kyushu Lipid Intervention Study (KLIS) was a clinical study for hypercholesterolemia, where pravastatin treatment was compared with conventional treatment. The primary endpoint was time to events of coronary heart disease (CHD). In this study, however, some subjects died from causes other than CHD or were censored due to loss to follow-up. Because the treatments were targeted to reduce CHD events, the investigators were interested in the effect of the treatment on CHD events in the absence of causes of death or events other than CHD. In this paper, we present a method for estimating treatment group-specific marginal survival curves of time-to-event data in the presence of dependent competing risks. The proposed method is a straightforward extension of the Inverse Probability of Censoring Weighted (IPCW) method to settings with more than one reason for censoring. The results of our analysis showed that the IPCW marginal incidence for CHD was almost the same as the lower bound for which subjects with competing events were assumed to be censored at the end of all follow-up. This result provided reassurance that the results in KLIS were robust to competing risks.
在医学研究中,人们对于推断受竞争风险影响的生存时间的边际分布很感兴趣。九州脂质干预研究(KLIS)是一项针对高胆固醇血症的临床研究,该研究将普伐他汀治疗与传统治疗进行了比较。主要终点是冠心病(CHD)事件发生的时间。然而,在这项研究中,一些受试者死于CHD以外的原因,或者由于失访而被截尾。由于治疗的目标是减少CHD事件,研究人员感兴趣的是在不存在除CHD以外的死亡原因或事件的情况下,治疗对CHD事件的影响。在本文中,我们提出了一种在存在相关竞争风险的情况下估计事件发生时间数据的治疗组特定边际生存曲线的方法。所提出的方法是将删失逆概率加权(IPCW)方法直接扩展到具有多个删失原因的情况。我们的分析结果表明,CHD的IPCW边际发病率几乎与假设具有竞争事件的受试者在所有随访结束时被截尾的下限相同。这一结果让人放心,即KLIS的结果对竞争风险具有稳健性。