Ontario Clinical Oncology Group, Dept of Oncology, McMaster University, 711 Concession Street, 60 (G) Wing, Hamilton, ON, L8V 1C3, Canada.
Contemp Clin Trials. 2011 Nov;32(6):829-33. doi: 10.1016/j.cct.2011.07.005. Epub 2011 Jul 18.
Patients with malignant disease enrolled in trials of thrombotic disorders may experience competing events such as death. The occurrence of a competing event may prevent the thrombotic event from being observed. Standard survival analysis techniques ignore competing risks, resulting in possible bias and distorted inferences. To assess the impact of competing events on the results of a previously reported trial comparing low molecular weight heparin (LMWH) with oral anticoagulant (OAC) therapy for the prevention of recurrent venous thromboembolism (VTE) in patients with advanced cancer, we compare the results from standard survival analysis with those from competing risk techniques which are based on the cumulative incidence function (CIF) and Gray's test. The Kaplan-Meier method overestimates the risk of recurrent VTE (17.2% in the OAC group and 8.7% in the LMWH group). Risk of recurrence using the CIF is 12.0% and 6.0% in the OAC and LMWH groups, respectively. Both the log-rank test (p=0.002) and Gray's test (p=0.006) suggest evidence in favor of LMWH. The overestimation of risk is 30% in each treatment group, resulting in a similar relative treatment effect; using the Cox model the hazard ratio (HR) is 0.48 (95% confidence interval [CI], 0.30 to 0.78) and HR=0.47 (95% CI, 0.29 to 0.74) using the CIF model. Failing to account for competing risks may lead to incorrect interpretations of the probability of recurrent VTE. However, when the distribution of competing risks is similar within each treatment group, standard and competing risk methods yield comparable relative treatment effects.
患有恶性疾病并参加血栓性疾病试验的患者可能会经历竞争事件，如死亡。竞争事件的发生可能会阻止血栓事件的发生。标准生存分析技术忽略了竞争风险，导致可能的偏差和扭曲的推论。为了评估竞争事件对先前报道的一项比较低分子肝素（LMWH）与口服抗凝剂（OAC）治疗晚期癌症患者复发性静脉血栓栓塞（VTE）的试验结果的影响，我们比较了标准生存分析与基于累积发生率函数（CIF）和 Gray 检验的竞争风险技术的结果。Kaplan-Meier 方法高估了复发性 VTE 的风险（OAC 组为 17.2%，LMWH 组为 8.7%）。使用 CIF 的复发风险分别为 OAC 组和 LMWH 组的 12.0%和 6.0%。对数秩检验（p=0.002）和 Gray 检验（p=0.006）均提示支持 LMWH 的证据。在每个治疗组中，风险的高估均为 30%，导致相似的相对治疗效果；使用 Cox 模型，风险比（HR）为 0.48（95%置信区间[CI]，0.30 至 0.78），使用 CIF 模型，HR 为 0.47（95%CI，0.29 至 0.74）。不考虑竞争风险可能导致对复发性 VTE 概率的不正确解释。然而，当每个治疗组内竞争风险的分布相似时，标准和竞争风险方法产生可比的相对治疗效果。
