Evaluating parents’ decisions about next-generation sequencing for their child in the NC NEXUS (North Carolina Newborn Exome Sequencing for Universal Screening) study: a randomized controlled trial protocol

Abstract

BackgroundUsing next-generation sequencing (NGS) in newborn screening (NBS) could expand the number of genetic conditions detected pre-symptomatically, simultaneously challenging current precedents, raising ethical concerns, and extending the role of parental decision-making in NBS. The NC NEXUS (Newborn Exome Sequencing for Universal Screening) study seeks to assess the technical possibilities and limitations of NGS-NBS, devise and evaluate a framework to convey various types of genetic information, and develop best practices for incorporating NGS-NBS into clinical care. The study is enrolling both a healthy cohort and a cohort diagnosed with known disorders identified through recent routine NBS. It uses a novel age-based metric to categorize a priori the large amount of data generated by NGS-NBS and interactive online decision aids to guide parental decision-making. Primary outcomes include: (1) assessment of NGS-NBS sensitivity, (2) decision regret, and (3) parental decision-making about NGS-NBS, and, for parents randomized to have the option of requesting them, additional findings (diagnosed and healthy cohorts). Secondary outcomes assess parents’ reactions to the study and to decision-making.Methods/designParticipants are parents and children in a well-child cohort recruited from a prenatal clinic and a diagnosed cohort recruited from pediatric clinics that treat children with disorders diagnosed through traditional NBS (goal of 200 children in each cohort). In phase 1, all parent participants use an online decision aid to decide whether to accept NGS-NBS for their child and provide consent for NGS-NBS. In phase 2, parents who consent to NGS-NBS are randomized to a decision arm or control arm (2:1 allocation) and learn their child’s NGS-NBS results, which include conditions from standard (non-NGS) NBS plus other highly actionable childhood-onset conditions. Parents in the decision arm use a second decision aid to make decisions about additional results from their child’s sequencing. In phase 3, decision arm participants learn additional results they have requested. Online questionnaires are administered at up to five time points.DiscussionNC NEXUS will use a rigorous interdisciplinary approach designed to collect rich data to inform policy, practice, and future research.Trial registrationclinicaltrials.gov, NCT02826694. Registered on 11 July, 2016.Electronic supplementary materialThe online version of this article (10.1186/s13063-018-2686-4) contains supplementary material, which is available to authorized users.

A behavior-theoretic evaluation of values clarification on parental beliefs and intentions toward genomic sequencing for newborns

“…This framework provides a conceptual approach to help explain how values clarification supports decision making under conditions of uncertainty (Bekker et al, 2003;Fagerlin et al, 2013;Nelson et al, 2007), and starts to address the underlying mechanisms related to values clarification. This study preceded the larger NC NEXUS trial (Milko et al, 2018), and was conducted to help us understand the role of the decision aid on actual decisions being made in the trial. In NC NEXUS, parents of newborns and parents of young children with a confirmed diagnosis are offered whole exome sequencing.…”

“…The decision aid content used in this study was developed for a larger project called the North Carolina Newborn Exome Sequencing for Universal Screening (NC NEXUS) study (Lewis et al, 2018;Milko et al, 2018). The NC NEXUS project aims to evaluate the utility of genomic sequencing as an alternative and extension to the currently administered newborn screening tests, to learn how parents make decisions about obtaining genomic sequencing for their child, and to investigate whether a decision aid would help them make informed decisions about genomic sequencing.…”

The Role of Technology in Newborn Screening

“…Approximately five years ago, the National Institute of Child Health and Human Development awarded grants worth $25 million to four centers in the United States, including the University of North Carolina, to study various aspects of next-generation DNA testing in newborns. The North Carolina project (NC-NEXUS) includes a research study to explore the utility of next-generation sequencing in newborn screening and parental decision-making [23]. The results of these studies will enable a deeper understanding of the issues surrounding DNA screening in newborns [20].…”

The Future of Newborn Screening

“…Today, the North Carolina State Laboratory of Public Health (NCSLPH) is implementing analyses of DNA mutations and other advanced molecular strategies to improve accuracy of screening for certain disorders. North Carolina researchers are investigating the implications of genome or exome sequencing for newborn screening [6], and industry developed methods are exploring the use of digital microfluidics for screening [7].…”