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 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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-06-01
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| Series: | Trials |
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| Online Access: | http://link.springer.com/article/10.1186/s13063-018-2686-4 |
| _version_ | 1819159607066492928 |
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| author | 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 Jonathan S. Berg Cynthia M. Powell |
| author_facet | 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 Jonathan S. Berg Cynthia M. Powell |
| author_sort | Laura V. Milko |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T16:43:14Z |
| format | Article |
| id | doaj.art-c62c667f2d384e65a239b9827d189cae |
| institution | Directory Open Access Journal |
| issn | 1745-6215 |
| language | English |
| last_indexed | 2024-12-22T16:43:14Z |
| publishDate | 2018-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Trials |
| spelling | doaj.art-c62c667f2d384e65a239b9827d189cae2022-12-21T18:19:48ZengBMCTrials1745-62152018-06-0119111410.1186/s13063-018-2686-4Evaluating 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 protocolLaura V. Milko0Christine Rini1Megan A. Lewis2Rita M. Butterfield3Feng-Chang Lin4Ryan S. Paquin5Bradford C. Powell6Myra I. Roche7Katherine J. Souris8Donald B. Bailey9Jonathan S. Berg10Cynthia M. Powell11Department of Genetics, University of North Carolina at Chapel HillDepartment of Biomedical Research, Hackensack University Medical CenterCenter for Communication Science, RTI InternationalDepartment of Pediatrics, University of North Carolina at Chapel Hill School of MedicineDepartment of Biostatistics, University of North Carolina at Chapel HillCenter for Communication Science, RTI InternationalDepartment of Genetics, University of North Carolina at Chapel HillDepartment of Pediatrics, University of North Carolina at Chapel Hill School of MedicineDepartment of Heath Behavior, Gillings School of Global Public Health, University of North Carolina at Chapel HillCenter for Newborn Screening, Ethics, and Disability Studies, RTI InternationalDepartment of Genetics, University of North Carolina at Chapel HillDepartment of Genetics, University of North Carolina at Chapel HillAbstract 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.http://link.springer.com/article/10.1186/s13063-018-2686-4Translational genomicsSequencingNewborn screeningParental decision aidRandomized trial |
| spellingShingle | 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 Jonathan S. Berg Cynthia M. Powell 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 Trials Translational genomics Sequencing Newborn screening Parental decision aid Randomized trial |
| 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Translational genomics Sequencing Newborn screening Parental decision aid Randomized trial |
| url | http://link.springer.com/article/10.1186/s13063-018-2686-4 |
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