Long-term Impact and Value of Infant Genomic Sequencing (LIVING)

PROJECT SUMMARY/ABSTRACT The use of genomic sequencing at birth to inform the ongoing care of children has generated great enthusiasm. Genomic sequencing can act as a screening tool for identifying newborns with existing genetic disorders; additionally, results can identify newborns with genetic predispositions for future disease that could

be prevented or mitigated through early intervention. In addition, genomic sequencing can help health care providers manage their patients’ medications by characterizing genes associated with drug metabolism and modifying medication choices accordingly. These applications and more have raised hopes that genomic

sequencing could complement traditional newborn screening and provide lifelong benefits to individuals and families. However, great uncertainties exist on how genomic sequencing should be implemented by health systems and how state newborn screening programs can help genomic sequencing achieve its potential. The

long-term impact of genomic sequencing results on the family are unclear, and projections about how genomics screening findings will be managed over time are predicated on unverified assumptions that families and health care providers will be able to access results over time and will continue to follow best practice

recommendations for surveillance of high-risk findings as individuals age. Moreover, the evolving evidence about gene-disease and gene-drug interactions raises questions about whether, when, and how frequently molecular laboratories should reanalyze genomic information. This proposal addresses these key questions about how to ensure newborn genomic sequencing provides

lifelong benefits and value. We will conduct key-informant interviews to understand the needs and concerns of clinicians, health system leaders, and coordinators of newborn screening programs regarding how newborn genomic sequencing should be implemented to complement traditional newborn screening, and what systems

need to be designed to maximize their utility over time for children and their families. We will also conduct follow-up studies of individuals who participated in prior clinical trials of newborn genomic sequencing to document how health care providers and families utilized genomic information as children aged, and to provide

insight about the benefits and harms that may have accrued. In addition, we will develop a mathematical model to project the lifelong benefits, harms and cost-effectiveness of different strategies for reanalyzing existing genomic information over time. The goal of this study is to provide critically-needed evidence about how to

implement newborn genomic sequencing, manage findings, and reanalyze data to ensure newborn genomic sequencing fulfills its promise as a tool that provides lifelong benefits to individuals and advances public health.