Walter S D, Gafni A, Birch S
Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ont., Canada.
Stat Med. 2008 Dec 10;27(28):5956-74. doi: 10.1002/sim.3398.
One is often interested in the ratio of two variables, for example in genetics, assessing drug effectiveness, and in health economics. In this paper, we derive an explicit geometric solution to the general problem of identifying the two tangents from an arbitrary external point to an ellipse. This solution permits numerical integration of a bivariate normal distribution over a wedge-shaped region bounded by the tangents, which yields an evaluation of the tangent slopes as confidence limits on the ratio of the component variables. After suitable adjustment of the confidence coverage of the ellipse, these confidence limits are shown to be equivalent to those from Fieller's method. However, the geometric approach allows additional interpretation of the data through identification of the points of tangency, the ellipse itself, and expressions for the coverage probability of the confidence interval. Numerical evaluations using the theoretical expressions for the geometric confidence intervals (but ignoring sample variation in the underlying parameters) suggested that they perform well overall and are slightly conservative. Simulations that do take account of sample variation in the underlying parameters again suggested that the intervals perform well overall, although here they are slightly anti-conservative. Coverage probabilities for the confidence intervals were only weakly dependent on the distance and correlation of the ellipse, but there were asymmetries in the failure rates of the upper and lower confidence limits in some configurations. The probability of no real solution existing was also evaluated. These ideas are illustrated by a practical example.
人们常常对两个变量的比率感兴趣,例如在遗传学、评估药物疗效以及健康经济学中。在本文中,我们针对从任意外部点向椭圆作两条切线这一一般问题,推导出了一个明确的几何解法。该解法允许对由切线界定的楔形区域上的二元正态分布进行数值积分,从而得出切线斜率的评估值,作为组成变量比率的置信限。在对椭圆的置信覆盖范围进行适当调整后,这些置信限被证明与菲勒方法得出的置信限等效。然而,几何方法通过切点的识别、椭圆本身以及置信区间覆盖概率的表达式,允许对数据进行额外的解释。使用几何置信区间的理论表达式进行数值评估(但忽略基础参数中的样本变化)表明,它们总体表现良好且略显保守。考虑到基础参数中的样本变化的模拟再次表明,这些区间总体表现良好,尽管在此情况下它们略显反保守。置信区间的覆盖概率仅微弱地依赖于椭圆的距离和相关性,但在某些配置中,上下置信限的失败率存在不对称性。还评估了不存在实解的概率。通过一个实际例子对这些想法进行了说明。