Cook R J, Major P
Department of Statistics and Actuarial Science, University of Waterloo, ON, Canada.
J Natl Cancer Inst. 2001 Apr 4;93(7):534-8. doi: 10.1093/jnci/93.7.534.
Patients with cancer metastatic to bone experience several adverse and clinically important skeletal-related events, including pathologic fractures, vertebral compressions with fracture, the need for surgery to treat or prevent fractures, and the need for radiation therapy for the treatment of bone pain. We present appropriate methods for describing and modeling the clinical course of skeletal-related events and comparing treatments for such events.
On the basis of data from a recently completed randomized, placebo-controlled trial involving 380 breast cancer patients with bone metastases, we tested the validity of the "events-per-person-years" method, one of the most commonly used techniques, for the analysis of skeletal-related events. We then used more robust methods of analysis that are based on fewer assumptions, including a random-effects Poisson model, and contrasted the inferences about skeletal-related event rates and treatment effects for the different analytic methods. All statistical tests were two-sided.
The events-per-person-years analysis underestimated substantially the variation in the data and is not appropriate to summarize the incidence rate of skeletal-related events. A random-effects Poisson model did provide a valid basis for analyzing such data.
The underestimation of variability in data associated with the use of the events-per-person-years analysis leads to unduly narrow confidence intervals for complication rates and inflated false-positive error rates in treatment comparisons. A random-effects Poisson model provides a valid, robust basis for describing the clinical course of bone complications and evaluating treatment effects.
发生骨转移的癌症患者会经历多种不良且具有临床重要性的骨相关事件，包括病理性骨折、伴有骨折的椎体压缩、治疗或预防骨折所需的手术，以及治疗骨痛所需的放射治疗。我们提出了描述和模拟骨相关事件临床病程以及比较此类事件治疗方法的合适方法。
基于一项近期完成的涉及380例乳腺癌骨转移患者的随机、安慰剂对照试验的数据，我们测试了“每人年事件数”方法（最常用的技术之一）用于分析骨相关事件的有效性。然后，我们使用了基于较少假设的更稳健分析方法，包括随机效应泊松模型，并对比了不同分析方法对骨相关事件发生率和治疗效果的推断。所有统计检验均为双侧检验。
“每人年事件数”分析大幅低估了数据的变异性，不适用于总结骨相关事件的发生率。随机效应泊松模型确实为分析此类数据提供了有效的基础。
与使用“每人年事件数”分析相关的数据变异性低估导致并发症发生率的置信区间过窄，以及治疗比较中假阳性错误率过高。随机效应泊松模型为描述骨并发症的临床病程和评估治疗效果提供了有效、稳健的基础。
