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, 19 (1), 344

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

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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

Laura V Milko et al. Trials.

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.

Keywords: Newborn screening; Parental decision aid; Randomized trial; Sequencing; Translational genomics.

Conflict of interest statement

Ethics approval and consent to participate

This study will be performed in accordance with the Declaration of Helsinki and has been approved by the Biomedical IRB of UNC (study 13-2409) and the U.S. FDA (investigational device exemption G150258). Protocol modifications are reported to and approved by the FDA and the UNC IRB. Informed consent will be obtained from all study participants.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Study design workflow. Three phases of the NC NEXUS study workflow. During phase 1, interested parents agree to learn more about the study and are asked to complete the time 1 pre-decision questionnaire and the time 2 post-decision assessment. Parents use the decision aid to learn about the study and NGS-NBS for their child and complete informed consent procedures at a clinic study visit if they decide to participate. During phase 2, samples are obtained after consent is given at study visit 1. Randomization status and NGS-NBS results are returned to parents at their second study visit. During phase 3, parents in the decision arm decide via a second part of the decision aid whether to consent to and receive any additional information by phone (for carrier status results) or at a third study visit. Parents randomized to the decision arm also complete a time 2A post-additional information decision assessment. Both the decision arm and the control arm complete a short-term follow-up assessment and a long-term follow-up assessment. NBS newborn screening, NGS next-generation sequencing
Fig. 2
Fig. 2
SPIRIT figure. Schedule of enrolment, interventions, and assessments. AI additional information, NBS newborn screening, NGS next-generation sequencing

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