Statistical models and methods for survival and longitudinal data in clinical and observational studies

由于癌症治疗研究的进步，越来越多的患者经历了更长的生存期并被治愈。在各种复杂的抽样设计和模型假设中，越来越需要适当的统计方法来考虑被治愈的对象。先进的技术也会产生各种形式的大数据，比如癌症生物学研究中的组织微阵列数据。在卫生服务研究中广泛使用观察性行政数据库也给大数据时代的因果推理带来了挑战。开发新的统计模型，估计方法，以及用于分析观察和临床研究中出现的截尾生存数据和纵向数据的配套软件一直是我们研究计划的主要主题。我们将继续这个研究项目，重点关注的问题包括，但不限于：1)开发模型评估工具和具有治愈部分的生存数据的灵活的非参数模型2)使用具有高维数据的边际生存模型和边际治愈模型正确建模相关生存时间和变量选择3)使用高维管理数据库确定治疗效果的因果推理4)组织微阵列数据的预测性生物标志物测定以及生存和纵向数据的联合模型。5)开发R包和SAS宏，用于建议的模型和方法，供公众使用。预计本研究将为统计学家处理高维临床和观察数据产生新的统计方法。该方法还将对收集和分析事件时间的自然科学和工程领域的可靠性等产生影响。这项研究不仅促进了统计模型和理论的新发展，而且由于开发了供公众使用的软件，以提高所提出的研究工作的可重复性和适用性，从而促进了从统计模型到统计应用的知识转移。该研究项目还将为从硕士生到博士后的学员提供合适的机会。

Due to advances in cancer treatment research, more patients are experiencing longer survival and becoming cured. There are increasing demands for appropriate statistical methods to take the cured subjects into account in various complicated sampling designs and models assumptions. Advanced technology also generates big data in various forms, such as tissue microarray data in cancer biology studies. The wide use of observational administrative databases for health service research also creates challenges in causal inferences in the era of big data.Developing novel statistical models, estimation methods, and accompanying software for analyzing censored survival data and longitudinal data arising in observational and clinical studies has been the primary topic of our research program. We will continue this research program with focus on issues including, but not limited to:1) Development of model assessment tools and flexible nonparametric models for survival data with a cured fraction2) Properly modeling correlated survival times and variable selection using marginal survival models and marginal cure models with high-dimensional data3) Causal inference to determine treatment effects with high-dimensional administrative databases4) Predictive biomarkers determination for tissue microarray data and joint models for survival and longitudinal data.5) Development of R packages and SAS macros for proposed models and methods for public useIt is anticipated that this research will generate new statistical methods for statisticians working with high-dimensional clinical and observational data. The new methods will also have impact on other fields of natural science and engineering where event times are collected and analyzed, such as reliability. The research stimulates not only new development in the statistics models and theory, but also knowledge transfer from statistical models to statistical applications due to the development of software for public use to enhance reproducibility and applicability of the proposed research work. The research program will also provide suitable opportunities for trainees at levels from masters students to post-doctoral fellows.