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Open Access 01-12-2018 | Study protocol

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

Authors: Laura V. Milko, Christine Rini, Megan A. Lewis, Rita M. Butterfield, Feng-Chang Lin, Ryan S. Paquin, Bradford C. Powell, Myra I. Roche, Katherine J. Souris, Donald B. Bailey Jr, Jonathan S. Berg, Cynthia M. Powell

Published in: Trials | Issue 1/2018

Abstract

Background

Using 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/design

Participants 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.

Discussion

NC NEXUS will use a rigorous interdisciplinary approach designed to collect rich data to inform policy, practice, and future research.

Trial registration

clinicaltrials.gov, NCT02826694. Registered on 11 July, 2016.

Available only for authorised users

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Title: 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
Authors: Laura V. Milko
Christine Rini
Megan A. Lewis
Rita M. Butterfield
Feng-Chang Lin
Ryan S. Paquin
Bradford C. Powell
Myra I. Roche
Katherine J. Souris
Donald B. Bailey Jr
Jonathan S. Berg
Cynthia M. Powell
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Trials / Issue 1/2018
Electronic ISSN: 1745-6215
DOI: https://doi.org/10.1186/s13063-018-2686-4

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

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

Background

Methods/design

Discussion

Trial registration

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods/design

Discussion

Trial registration

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