Fong Youyi, Di Chongzhi, Permar Sallie
Vaccine and Infectious Disease Division and Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98006, U.S.A.
Stat Med. 2015 Apr 30;34(9):1483-94. doi: 10.1002/sim.6419. Epub 2015 Jan 22.
A threshold effect takes place in situations where the relationship between an outcome variable and a predictor variable changes as the predictor value crosses a certain threshold/change point. Threshold effects are often plausible in a complex biological system, especially in defining immune responses that are protective against infections such as HIV-1, which motivates the current work. We study two hypothesis testing problems in change point models. We first compare three different approaches to obtaining a p-value for the maximum of scores test in a logistic regression model with change point variable as a main effect. Next, we study the testing problem in a logistic regression model with the change point variable both as a main effect and as part of an interaction term. We propose a test based on the maximum of likelihood ratios test statistic and obtain its reference distribution through a Monte Carlo method. We also propose a maximum of weighted scores test that can be more powerful than the maximum of likelihood ratios test when we know the direction of the interaction effect. In simulation studies, we show that the proposed tests have a correct type I error and higher power than several existing methods. We illustrate the application of change point model-based testing methods in a recent study of immune responses that are associated with the risk of mother to child transmission of HIV-1.
阈值效应发生在结果变量与预测变量之间的关系随着预测值跨越某个阈值/变化点而改变的情况下。在复杂的生物系统中,阈值效应通常是合理的,特别是在定义针对诸如HIV-1等感染具有保护作用的免疫反应时,这激发了当前的研究工作。我们研究了变点模型中的两个假设检验问题。我们首先比较了三种不同的方法,以在以变点变量作为主要效应的逻辑回归模型中获得得分检验最大值的p值。接下来,我们研究了变点变量既作为主要效应又作为交互项一部分的逻辑回归模型中的检验问题。我们提出了一种基于似然比检验统计量最大值的检验方法,并通过蒙特卡罗方法获得其参考分布。当我们知道交互效应的方向时,我们还提出了一种加权得分检验最大值,它可能比似然比检验最大值更具功效。在模拟研究中,我们表明所提出的检验具有正确的I型错误率,并且比几种现有方法具有更高的功效。我们说明了基于变点模型的检验方法在最近一项与HIV-1母婴传播风险相关的免疫反应研究中的应用。