TY - JOUR
T1 - Evaluating parents' decisions about next-generation sequencing for their child in the NC NEXUS (North Carolina Newborn Exome Sequencing for Universal Screening) study
T2 - A randomized controlled trial protocol
AU - Milko, Laura V.
AU - Rini, Christine Marie
AU - Lewis, Megan A.
AU - Butterfield, Rita M.
AU - Lin, Feng Chang
AU - Paquin, Ryan S.
AU - Powell, Bradford C.
AU - Roche, Myra I.
AU - Souris, Katherine J.
AU - Bailey, Donald B.
AU - Berg, Jonathan S.
AU - Powell, Cynthia M.
N1 - Funding Information:
The authors would like to acknowledge important contributions to this study made by Samuel Demers, Karen Dorman, James P. Evans, Ann Katherine Foreman, Amber Ivins, Marjorie Margolis, Julianne O'Daniel, Phillips Owen, Kirk Wilhelmsen, and the North Carolina Translational and Clinical Sciences Institute, National Institutes of Health (grant 1UL1TR001111). The NC NEXUS study is funded by grant U19HD077632 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Human Genome Research Institute (RFA-HD-13-010).
Funding Information:
The NC NEXUS study is funded by grant U19HD077632 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Human Genome Research Institute (RFA-HD-13-010).
Funding Information:
NC NEXUS is one of four projects run by the Newborn Sequencing in Genomic Medicine and Public Health (NSIGHT) consortium, jointly funded by the Eunice Kennedy Shriver National Institute for Child Health and Human Development and the National Human Genome Research Institute. These studies explore, in a limited but deliberate manner, the implications, challenges, and opportunities associated with the possible use of genomic sequence information in the newborn period [11]. Each NSIGHT project acquires and analyzes genomic datasets that considerably expand the scale of data that has historically been available for analysis in the newborn period.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/6/28
Y1 - 2018/6/28
N2 - 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.
AB - 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.
KW - Newborn screening
KW - Parental decision aid
KW - Randomized trial
KW - Sequencing
KW - Translational genomics
UR - http://www.scopus.com/inward/record.url?scp=85049131113&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85049131113&partnerID=8YFLogxK
U2 - 10.1186/s13063-018-2686-4
DO - 10.1186/s13063-018-2686-4
M3 - Article
C2 - 29950170
AN - SCOPUS:85049131113
SN - 1745-6215
VL - 19
JO - Trials
JF - Trials
IS - 1
M1 - 344
ER -
