Marubini E, Montoro C, Mezzanotte G, Petroccione A, Cataldo G, Rovelli F
Istituto di Statistica Medica e Biometria, Università di Milano, Italy.
Control Clin Trials. 1990 Dec;11(6):420-32. doi: 10.1016/0197-2456(90)90019-x.
In clinical trials carried out to assess the efficacy of different drugs in reducing the frequency of occlusion after coronary artery bypass, the ratio of the number of patients with at least one occluded anastomosis to the number of patients catheterized up to a given day is a widely adopted statistic. In the early evaluation (at 1 or 2 months after surgery), this is affected by the distribution of timing of angiography and it tends to underestimate the cumulative probability of occlusion because patients whose anastomoses are all patent at angiography and occlude between angiography and the day at which the ratio is estimated do not contribute their events to the numerator of the ratio. One may sensibly assume that this underestimate does not affect the evaluation of the efficacy of treatments tested "within" the trial. In contrast, since the distributions of the timing of angiography vary substantially from trial to trial, it can make comparisons "between" trials unclear and possibly biased. The aim of this article is to suggest an alternative approach of statistical analysis in terms of logistic regression. By modeling the dichotomous response given by each patient in function of time at angiography, type of treatment, and other possible covariates, asymptotically unbiased estimates of the cumulative probability of occlusion are attained. Furthermore, the pertinent hazard function can be estimated. The main features of the model are discussed and the results obtained by fitting early data collected in the Studio Indobufen Nel Bypass Aortocoronarico (SINBA) are given.
在评估不同药物降低冠状动脉搭桥术后血管闭塞发生率疗效的临床试验中，截至给定日期，至少有一处吻合口闭塞的患者数量与接受导管检查的患者数量之比是一种广泛采用的统计数据。在早期评估（术后1或2个月）时，这一数据受血管造影时间分布的影响，并且往往会低估闭塞的累积概率，因为血管造影时吻合口均通畅但在血管造影与计算该比例之日之间发生闭塞的患者，其事件未计入该比例的分子中。可以合理地假定，这种低估不会影响对试验“内部”所测试治疗效果的评估。相比之下，由于不同试验的血管造影时间分布差异很大，这可能会使试验“之间”的比较不明确且可能产生偏差。本文的目的是提出一种基于逻辑回归的统计分析替代方法。通过对每位患者在血管造影时间、治疗类型及其他可能协变量作用下给出的二分反应进行建模，可以得到闭塞累积概率的渐近无偏估计。此外，还可以估计相关的风险函数。文中讨论了该模型的主要特征，并给出了拟合吲哚布芬在主动脉冠状动脉搭桥术研究（SINBA）中收集的早期数据所得到的结果。
