An ELSI-Integrated Evaluation of the Family-Level Utility of Pediatric Genomic Sequencing

项目总结/摘要 大量的资源已经投入到临床基因组测序的政策评估中， 效用的概念化和度量。然而，大多数评价未能充分利用 基因组测序，因为它们不考虑对家庭成员的影响。儿科是一个临床领域， 由于遗传性疾病的临床性质， 儿童和患者-父母-医生决策背景，除了潜在的识别 患者的生物学亲属可能受益于基因筛查。虽然传统的决策科学 卫生经济学评价方法以决策者依赖的形式产生证据，他们倾向于 关注个体患者，不考虑检测的伦理、法律的和社会影响（ELSI） 为家庭。跨学科的努力是必要的，整合影响临床实施的ELSI问题 和家庭偏好，使用决策科学方法进行稳健的建模和结果评估。这 独立之路奖（K99/R 00）将使候选人（卫生经济学家）具备以下方面的专业知识： ELSI，以便使用集成ELSI的决策科学方法进行创新研究 注意事项。候选人的职业目标是成为一名独立研究的终身教授 该计划旨在有意义地评估基因组医学的影响，并扩大政策的证据基础 决定其实施。拟议研究的目标是开发一种临床相关的， ELSI知情模型，以评估儿科临床背景下基因组测序对家庭水平的影响 在乎在贝勒医学院医学伦理和健康政策中心工作，候选人将 在项目的指导阶段（K99），在三个领域进行培训：（1）ELSI，包括定性 研究方法和规范伦理;（2）儿科遗传学临床背景;（3）先进的决策科学 方法，包括患者偏好的启发和决策分析模型。培训将适用于 进行研究，以更好地了解儿科临床基因组学在家庭层面的效用， ELSI和家庭偏好。研究项目的具体目标是：（1）识别相关属性， 儿童基因组测序的家庭水平评估的规范值;（2）检查父母如何重视 这些属性的基因组测序使用离散选择实验;（3）开发决策分析 儿科基因组测序的家庭水平影响模型，以检查其作为诊断工具的使用， 探讨包括ELSI和家庭偏好的效用措施的重要性。该项目将具有高 通过推进基因组医学的效用评估，更好地指导临床和政策决策， 制作。结果将为临床指南、报销策略和伦理实施提供信息， 儿科基因组测序，以改善患者和人群的健康。

PROJECT SUMMARY/ABSTRACT Substantial resources have been devoted to policy evaluation of clinical genomic sequencing that hinge on the conceptualization and measurement of utility. However, most evaluations fail to capture the full utility of genomic sequencing because they do not account for impact on family members. Pediatrics is a clinical area in which study of family impact is imperative due to the clinical nature of genetic disorders that manifest in childhood and the patient-parent-physician decision-making context, in addition to potential identification of patients’ biologic relatives who may benefit from genetic screening. Although traditional decision science methods for health economic evaluation produce evidence in the form decision-makers rely upon, they tend to focus on the individual patient and do not consider the ethical, legal, and social implications (ELSI) of testing for families. Cross-disciplinary effort is necessary integrate ELSI issues that influence clinical implementation and family preferences using decision science methods for robust modeling and outcomes assessment. This Pathway to Independence Award (K99/R00) will equip the candidate, a health economist, with expertise in ELSI in order to conduct innovative research using decision science methodology that integrates ELSI considerations. The candidate’s career goal is to be a tenure track professor with an independent research program to meaningfully evaluate the impact of genomic medicine and expand the evidence base for policy decisions about its implementation. The goal of the proposed research is to develop a clinically relevant and ELSI-informed model to assess family-level impact of genomic sequencing in the context of pediatric clinical care. Based in the Center for Medical Ethics and Health Policy at Baylor College of Medicine, the candidate will pursue training in three domains during the mentored phase of the project (K99): (1) ELSI, including qualitative research methods and normative ethics; (2) pediatric genetics clinical context; (3) advanced decision science methods, including patient preference elicitation and decision analytic modeling. The training will be applied to conduct research to better understand the utility of pediatric clinical genomics at the family level by considering ELSI and family preferences. The specific aims of the research project are: (1) identify relevant attributes and normative values for family-level evaluation of pediatric genomic sequencing; (2) examine how parents value those attributes of genomic sequencing using a discrete choice experiment; (3) develop a decision analytic model of family-level impact of pediatric genomic sequencing to examine its use as a diagnostic tool and explore the importance of including ELSI and family preferences in utility measures. This project will have high impact by advancing utility assessment of genomic medicine to better guide clinical and policy decision- making. Results will inform clinical guidelines, reimbursement strategies, and ethical implementation of pediatric genomic sequencing to improve patient and population health.