Precision Medicine Policy and Treatment (PreEMPT) Model II

项目摘要/摘要 基因组测序与日常医疗实践的整合已经开始。在我们的第一个资助期， 精准医疗政策和治疗模式(PREMPT)I，我们开始探索其好处和风险 与新生儿的基因组测序有关，这有令人信服的逻辑：它可以提供临床上可行的 全面预防疾病或促进儿童或成人早期发现疾病的见解。 尽管新生儿基因组测序和家庭成员的级联测试在临床上是有用的， 问题仍然存在：新生儿基因组测序的成本效益、对疾病发病率的长期影响 和死亡率以及与诊断和治疗相关的费用。要填补这些知识空白非常重要，因为 对基因组测序广泛应用的期望。 我们提议的研究将通过扩展我们现有的计算机微观模拟模型来创建Preempt II 在Preempt I中开发，以反映新生儿基因组测序对更广泛的儿童- 发病疾病及其在成年后的长期后果。此外，我们将改进我们的方法，以 考虑到对患有病原变异的儿童的兄弟姐妹进行有针对性的筛查的影响。此前，我们 开发了一个评估儿科癌症和心脏疾病新生儿基因组测序的框架。在……里面 这次更新，我们将扩展这一框架，以评估代谢的临床好处和成本效益 庞贝病和生物素酶缺乏症等疾病以及恶性疾病等 体温过高。为了突出关键的知识差距，我们将使用信息分析的价值来确定高 在快速发展的基因组医学领域内的优先研究，重点是解决种族问题- 基于健康差异。我们将增强我们现有的模拟模型，以合成最好的可用临床， 流行病学和经济数据，并使用我们的分析框架来预测短期和长期结果 与其他筛选策略相关联，并评估基因组测序的潜在价值 缩小疾病结局中的种族差异。 我们的跨学科团队包括模拟建模、卫生经济学、基因组学、儿科、 预测性建模、卫生政策和卫生系统研究。我们提出了一种高度创新的应用 基因组技术的建模方法，目标是综合现有的临床和流行病学 数据整合到统一的建模工作中。其目标是通过将不断变化的数据整合到 新生儿基因组测序领域，允许随时评估和指导临床护理 美国在接下来的几十年里。

PROJECT SUMMARY/ABSTRACT Integration of genomic sequencing into everyday medical practice has already begun. In our first funding period, Precision Medicine Policy and Treatment Model (PreEMPT) I, we began exploring the benefits and risks associated with genomic sequencing in newborns, which has compelling logic: It can provide clinically actionable insights to prevent illness altogether or to facilitate early detection of illnesses in childhood or adulthood. Notwithstanding the clinical utility of newborn genomic sequencing and cascade testing of family members, questions remain: cost-effectiveness of newborn genomic sequencing, long-term effects on disease morbidity and mortality, and diagnostic and treatment-related costs. These knowledge gaps are important to fill, given expectations about widespread applications of genomic sequencing. Our proposed research will create PreEMPT II by extending our existing computer microsimulation model developed in PreEMPT I to reflect the impact of newborn genomic sequencing on a wider array of childhood- onset diseases and their long-term consequences into adulthood. Additionally, we will refine our approach to considering the impact of targeted screening of siblings of children with pathogenic variants. Previously, we developed a framework to evaluate newborn genomic sequencing for pediatric cancer and cardiac diseases. In this renewal, we will extend this framework to evaluate the clinical benefits and cost-effectiveness for metabolic diseases such as Pompe disease and biotinidase deficiency, and other diseases such as malignant hyperthermia. To highlight critical knowledge gaps, we will use value of information analysis to identify high- priority research studies within the rapidly evolving area of genomic medicine with a focus on addressing race- based health disparities. We will enhance our existing simulation model to synthesize the best available clinical, epidemiologic and economic data, and use our analytic framework to project both short- and long-term outcomes associated with alternative screening strategies and assess the potential value of genomic sequencing in reducing racial disparities in disease outcomes. Our interdisciplinary team includes experts in simulation modeling, health economics, genomics, pediatrics, predictive modeling, health policy, and health systems research. We propose a highly innovative application of modeling methods to genomic technologies with the goal of synthesizing available clinical and epidemiological data into a unified modeling effort. The goal is to project long-term outcomes by incorporating evolving data in the area of genomic sequencing for newborns, permitting ready evaluation and guidance for clinical care in the United States over the next decades.