Cancer Emulation Analysis with Deep Neural Network

项目概要 客观量化药物、设备和治疗程序对癌症的相对有效性 对于预后而言，严格设计和执行的随机临床试验（RCT）仍然是黄金标准。 然而，正如本申请和许多已发表的研究中所例证的那样，随机对照试验并不总是可行的。 幸运的是，电子病历和保险理赔数据库的快速发展使得 可以挖掘大量观测数据并有效补充RCT。这一策略已被 受到多个国家机构的热烈支持。在可用的观测数据分析中 旨在得出 RCT 类型结论的技术，仿真因其试验而显得特别有吸引力 比如架构、可解释性和可扩展性。它已被应用于多种癌症和其他复杂的疾病 疾病并得出具有临床意义的发现。 这项研究有两个同样重要的目标。第一个目标是开发基于深度神经网络（DNN）的 仿真分析方法和软件。现有的仿真分析大多基于经典的 回归技术。与回归相比，DNN 具有优越的模型拟合和更高的灵活性。 最近，我们课题组率先开发了基于DNN的仿真分析方法，并将其应用于 心血管疾病。在最近的成功基础上，我们将开发更多可解释性和更多内容 专为 RCT 分析而定制的稳定 DNN。然后我们将进一步扩大分析范围，进行基于DNN的分析 分析一系列模拟试验。对于单个模拟试验和一系列试验，我们将 建立有效的推理，这对于 RCT 分析至关重要，但在大多数 DNN 研究中都被忽视了。用户- 将开发友好的软件。这种方法论的发展将大大扩展 仿真分析、深度学习、因果推理、观察数据分析、病历/保险 索赔数据分析。第二个目标是开发和分析两个模拟试验。我们将解决 (a) 肺叶切除术和有限切除术对 SEER-Medicare 肺癌生存率的比较效果 老年人群，以及（b）根治性前列腺切除术和局限性前列腺癌生存观察 弗吉尼亚州人口。将对调查结果进行全面、严格的评估。为了提供更全面的 图片中，我们还将使用多种替代方法进行分析，并与现有的随机对照试验进行比较 观察性研究。凭借显着的方法论进步和强大的数据，我们的分析将 产生更明确的发现，直接为临床实践提供信息，并作为未来应用的原型。

Project Summary To objectively quantify the relative effectiveness of drugs, devices, and treatment procedures on cancer prognosis, rigorously designed and executed randomized clinical trials (RCTs) remain the gold standard. However, as exemplified in this application and many published studies, RCTs are not always feasible. Fortunately, the fast development of electronic medical records and insurance claims databases has made it possible to mine a large amount of observational data and efficiently complement RCTs. This strategy has been enthusiastically endorsed by multiple national organizations. Among the available observational data analysis techniques that aim to draw RCT-type conclusions, emulation has emerged as especially appealing, with its trial- like architecture, interpretability, and scalability. It has been applied to multiple cancers and other complex diseases and led to clinically significant findings. This study has two equally important aims. The first aim is to develop deep neural network (DNN)-based emulation analysis methods and software. Most of the existing emulation analyses are based on classic regression techniques. Compared to regression, DNN excels with superior model fitting and higher flexibility. Recently, our group was the first to develop a DNN-based emulation analysis approach and applied it to cardiovascular diseases. Advancing from this recent success, we will develop more interpretable and more stable DNNs tailored to RCT analysis. We will then further expand the analysis scope and conduct DNN-based analysis of a sequence of emulated trials. For both a single emulated trial and a sequence of trials, we will develop valid inference, which is essential for RCT analysis but has been neglected in most DNN studies. User- friendly software will be developed. This methodological development will substantially expand the scope of emulation analysis, deep learning, causal inference, observation data analysis, and medical record/insurance claims data analysis. The second aim is to develop and analyze two emulated trials. We will address the comparative effectiveness of (a) lobectomy and limited resection on lung cancer survival for the SEER-Medicare elderly population, and (b) radical prostatectomy and observation on localized prostate cancer survival for the VA population. The findings will be comprehensively and rigorously evaluated. To provide a more comprehensive picture, we will also analyze using multiple alternative methods and compare against existing RCTs and observational studies. With the significant methodological advancements and powerful data, our analysis will lead to more definitive findings, directly inform clinical practice, and serve as the prototype for future applications.