Fu Pingfu, Laughlin Mary J, Zhang Heping
Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH 44106, USA.
Contemp Clin Trials. 2006 Apr;27(2):174-82. doi: 10.1016/j.cct.2005.10.003. Epub 2005 Dec 2.
Bone marrow transplantation including autologous, allogeneic and syngeneic has evolved over the past 30 years into an effective therapy for patients with a variety of hematologic malignancies. A total of 51 patients with hematologic disorders were treated with myeloablation and transplantation with either unrelated human leucocyte antigen (HLA) partially matched umbilical cord blood or HLA-matched unrelated donor grafts during 1997-2003. In evaluation of survival of these patients, the log rank and Wilcoxon tests lead to ambiguous results, which also happen in other applications. While the asymptotic properties of these tests are well understood, it is not clear how they behave in a small and specific sample. To resolve the ambiguity and to better understand our patient sample, we compare the power of the two tests by simulation in small samples with piecewise log-logistic and Weibull distributions and with different censoring distributions. Our simulation study confirms the well known fact that when the hazards of underlying survival distributions are non-proportional early on, say t < t(0), but proportional when t> or = t(0), the Wilcoxon test has more power than log rank test. But the importance of our simulation is to gain insight into the time point and impact of t(0) with respect to our transplantation study of leukemia cancer patients. We now conclude that overall survivals of patients with two graft sources are statistically significantly different, in part due to the delay of neutrophil recovery of one patient population immediately after transplantation. Thus, we recommend that Wilcoxon test should be used in future studies of similarly designed clinical trials.
包括自体、异体和同基因骨髓移植在内,在过去30年里已发展成为治疗各种血液系统恶性肿瘤患者的有效疗法。1997年至2003年期间,共有51例血液系统疾病患者接受了清髓治疗,并移植了人类白细胞抗原(HLA)部分匹配的无关脐血或HLA匹配的无关供体移植物。在评估这些患者的生存率时,对数秩检验和Wilcoxon检验得出了模棱两可的结果,这在其他应用中也会出现。虽然对这些检验的渐近性质有很好的理解,但不清楚它们在小样本和特定样本中的表现如何。为了解决这种模糊性并更好地了解我们的患者样本,我们通过模拟比较了这两种检验在具有分段对数逻辑分布和威布尔分布以及不同删失分布的小样本中的检验效能。我们的模拟研究证实了一个众所周知的事实,即当潜在生存分布的风险在早期(比如t < t(0))不成比例,但在t ≥ t(0)时成比例时,Wilcoxon检验比对数秩检验具有更高的检验效能。但我们模拟的重要性在于深入了解t(0)相对于我们白血病癌症患者移植研究的时间点和影响。我们现在得出结论,两种移植物来源患者的总体生存率在统计学上有显著差异,部分原因是一组患者在移植后中性粒细胞恢复延迟。因此,我们建议在未来类似设计的临床试验研究中应使用Wilcoxon检验。