Statistical Methods for Ordinal Variables in HIV/AIDS Studies

描述(由申请人提供)：艾滋病毒/艾滋病生物医学研究中的许多重要变量都是按类别排序的。一些例子包括世卫组织的临床分期、教育水平、冲洗频率、宫颈病变分期、自我报告的避孕套使用情况以及双等位基因。虽然序数变量很常见，但缺乏解释其有序性的统计方法，特别是当序数变量是预测变量时。大多数标准方法要么将序数预测器视为绝对的(忽略顺序信息)，要么将序数预测器视为连续的(进行线性假设)。这一建议发展了统计方法，说明了有序变量的有序性质，而不做线性假设。这些方法处理以下情况：预测变量(X)是按类别排序的；结果变量(Y)是连续的、离散的、计数的、事件发生的时间或重复测量；以及存在多个协变量(Z)。一般的方法是对Z上的Y和Z上的X分别拟合合适的回归模型，然后检验这两个模型的残差之间的相关性。因此，这些方法依赖于有序分类数据的残差的新定义。评估了该残差的统计特性，以及它在模型诊断中的使用。计算了基于残差的检验统计量的渐近性质，推导了与其他方法的关系，开发了实现这些方法的用户友好的软件，并用模拟数据和真实数据研究了新方法的优点。这些方法被应用于两项艾滋病毒研究：第一项是使用边际结构模型评估冲洗频率对一群青春期女性中性传播感染的影响。第二个数据应用程序寻找与药物血浆水平、病毒学失败和患者毒副作用相关的人类遗传多态，这些患者启动了基于Eefavirenz或Aabacavir的抗逆转录病毒方案。 与公共卫生相关：新方法被输入计算机软件，并应用于以下研究：1)冲洗对青春期女性性传播感染的影响，2)哪些患者可能能够更好地对基于遗传模式的特定艾滋病毒治疗做出反应。

DESCRIPTION (provided by applicant): Many important variables in biomedical studies of HIV/AIDS are ordered categorical. A few examples include WHO clinical stage, level of education, frequency of douching, stage of cervical lesions, self- reported condom use, and biallelic genotypes. Although ordinal variables are common, statistical methods that account for their ordered nature are lacking, particularly when the ordinal variable is a predictor variable. Most standard methods either treat the ordinal predictor as categorical (ignoring the order information) or continuous (making linearity assumptions). This proposal develops statistical methods that account for the ordered nature of ordinal variables without making linearity assumptions. The methods address situations when a predictor variable (X) is ordered categorical; the outcome variable (Y) is continuous, discrete, counts, time-to-event, or repeated measures; and there are multiple covariates (Z). The general approach is to fit appropriate regression models of Y on Z, and X on Z, and then to test for correlation between the residuals from these two models. The methods therefore rely on a new definition of residual for ordered categorical data. Statistical properties of this residual are evaluated, as well as its use in model diagnostics. Asymptotic properties of the residual- based test statistics are computed, relationships with other methods are derived, user-friendly software that implements these methods is developed, and the advantages of the new methods are studied using simulated and real data. The methods are applied to two HIV studies: The first assesses the effect of the frequency of douching on sexually transmitted infections among a cohort of adolescent females using marginal structural models. The second data application looks for human genetic polymorphisms associated with drug plasma levels, virologic failure, and toxicities for patients initiating an efavirenz- or abacavir-based antiretroviral regimen. PUBLIC HEALTH RELEVANCE: The new methods are put into computer software and applied to studies of 1) the effect of douching on sexually transmitted infections among adolescent females, and 2) which patients may be able to better respond to specific HIV-treatments based on genetic patterns.