Targeted Empirical Super Learning in HIV Research

HIV 研究中有针对性的实证超级学习

• 批准号: 7649489
• 负责人: Mark J Vanderlaan
• 金额: $ 46.81万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7649489
• 关键词: AIDS prevention; AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Address; Adherence; Affect; Algorithms; Anti-Retroviral Agents; Area; CD4 Lymphocyte Count; CD4 Positive T Lymphocytes; Categories; Cell Count; Clinical; Collaborations; Communities; Computer software; Data; Dimensions; Disease Progression; Documentation; Drug Combinations; Drug resistance; Educational process of instructing; Elements; Future; Genotype; HIV; HIV Seropositivity; Hand; Health Insurance; Immunologics; In Vitro; Insurance Coverage; Lead; Learning; Left; Machine Learning; Measures; Mediating; Methodology; Methods; Modeling; Mutation; Nucleosides; Observational Study; Outcome; Pathway interactions; Patients; Pattern; Performance; Pharmaceutical Preparations; Plasma; Predisposition; Principal Investigator; Protease Inhibitor; Public Health Schools; RNA; Randomized; Recording of previous events; Relative (related person); Research; Research Personnel; Research Project Grants; Resistance; Resources; Scientist; Techniques; Testing; Time; Treatment Protocols; Validation; Viral; Viral Load result; Writing; antiretroviral therapy; base; density; indexing; inhibitor/antagonist; interest; novel; open source; programs; response; tool; treatment effect; user friendly software; user-friendly

DESCRIPTION (provided by applicant): The aim of this project is to study and extend a general statistical methodology, called Targeted Empirical Learning, which includes a recently developed Targeted Maximum Likelihood methodology. The fundamental theoretical underpinnings of this new and unified approach to statistical learning have been developed and we propose to expand Targeted Empirical Learning into a practical product that can be applied to pressing scientific questions. Building on long-standing collaborations with leading scientists in the areas of clinical AIDS research, we will use this novel methodology to address research questions concerning HIV. Given observed data consisting of a realization of n independently and identically distributed random variables, Targeted Empirical Learning employs the following elements: i) defining the parameter of interest; 2) modeling the parameter of interest, leaving the nuisance parameters unspecified or only including truly known modeling assumptions; 3) developing targeted robust and highly efficient (maximum likelihood) estimators of the parameter of interest. The methodology relies on unified cross- validation to choose between competitive estimators indexed by, for example, choices of sieves parameterizations, algorithms, and/or dimension reductions (in particular for the nuisance parameters). Importantly, the cross-validation criterion employed evaluates the performance of these candidate estimators with respect to the parameter of interest. Specific applications to be addressed include the following: i) develop models and corresponding targeted empirical learners of optimal individualized treatment rules for treating HIV-infected patients, 2) estimate measures of variable importance/causal effects for mutations in the HIV virus for predicting clinical response to drug combinations; 3) estimate causal effects of adherence profiles on virologic suppression for HIV-infected patients. We will further develop and apply a novel resampling-based multiple testing methodology to properly address our simultaneous testing and estimation of many scientific parameters of interest.

描述（由申请人提供）：该项目的目的是研究和扩展一种通用的统计方法，称为有针对性的经验学习，其中包括最近开发的有针对性的最大似然方法。这种新的统一的统计学习方法的基本理论基础已经开发出来，我们建议将有针对性的经验学习扩展为一个实用的产品，可以应用于紧迫的科学问题。在与艾滋病临床研究领域的领先科学家长期合作的基础上，我们将使用这种新颖的方法来解决有关艾滋病毒的研究问题。给定由n个独立且相同分布的随机变量的实现组成的观测数据，目标经验学习采用以下元素：i）定义感兴趣的参数; 2）对感兴趣的参数进行建模，使讨厌的参数未指定或仅包括真正已知的建模假设; 3）开发感兴趣的参数的目标鲁棒且高效（最大似然）的估计。该方法依赖于统一的交叉验证，以在通过例如筛选参数化、算法和/或降维（特别是对于讨厌的参数）的选择索引的竞争估计量之间进行选择。重要的是，采用的交叉验证标准评估这些候选估计相对于感兴趣的参数的性能。要解决的具体应用包括以下：i）开发用于治疗HIV感染患者的最佳个体化治疗规则的模型和相应的目标经验学习者，2）估计HIV病毒突变的可变重要性/因果效应的度量，以预测对药物组合的临床反应; 3）估计依从性概况对HIV感染患者的病毒学抑制的因果效应。我们将进一步开发和应用一种新型的基于重采样的多重测试方法，以正确解决我们对许多感兴趣的科学参数的同时测试和估计问题。