TY - JOUR
T1 - Evaluating the clinical utility of early exome sequencing in diverse pediatric outpatient populations in the North Carolina Clinical Genomic Evaluation of Next-generation Exome Sequencing (NCGENES) 2 study
T2 - a randomized controlled trial
AU - Staley, Brooke S.
AU - Milko, Laura V.
AU - Waltz, Margaret
AU - Griesemer, Ida
AU - Mollison, Lonna
AU - Grant, Tracey L.
AU - Farnan, Laura
AU - Roche, Myra
AU - Navas, Angelo
AU - Lightfoot, Alexandra
AU - Foreman, Ann Katherine M.
AU - O’Daniel, Julianne M.
AU - O’Neill, Suzanne C.
AU - Lin, Feng Chang
AU - Roman, Tamara S.
AU - Brandt, Alicia
AU - Powell, Bradford C.
AU - Rini, Christine
AU - Berg, Jonathan S.
AU - Bensen, Jeannette T.
N1 - Funding Information:
The NCGENES 2 study is funded by Grant Number #U01HG006487 from the National Human Genome Research Institute (NHGRI). The National Research Service Award from the Agency for Healthcare Research and Quality (T32 HS000032) supported I. Griesemer and the Genetic Epidemiology of Heart, Lung, and Blood (HLB) Traits Training Grant (GenHLB, T32HL129982) supported B.S. Staley for the writing of this manuscript. Trial funders had no role in the study design, collection, analysis, and interpretation of data nor in writing this manuscript.
Funding Information:
NCGENES 2 is carried out as a collaborative study supported by the National Hufman Genome Research Institute, National Cancer Institute, and National Institute of Minority Health and Health Disparities of the National Institutes of Health for RFA-HG-12-009 under Award Number U01HG006487. The authors thank the Clinical Sequencing Evidence-Generating Research consortium, and staff, advisory committees, and families participating in the NCGENES 2 study for their significant contributions. The authors would also like to acknowledge important contributions to this study made by the entire NCGENES 2 team, the High-Throughput Sequencing Facility at UNC, the Renaissance Computing Institute, the Mission Fullerton Genetics Lab, the Carolina Data Warehouse for Health, and the North Carolina Translational and Clinical Sciences Institute. We want to acknowledge the UNC BioSpecimen Processing Facility (https://genome.unc.edu/bsp) and the UNC Health Molecular Genetics Laboratory for our DNA extractions, blood processing, storage, and sample disbursement.
Funding Information:
NCGENES 2 is carried out as a collaborative study supported by the National Hufman Genome Research Institute, National Cancer Institute, and National Institute of Minority Health and Health Disparities of the National Institutes of Health for RFA-HG-12-009 under Award Number U01HG006487. The authors thank the Clinical Sequencing Evidence-Generating Research consortium, and staff, advisory committees, and families participating in the NCGENES 2 study for their significant contributions. The authors would also like to acknowledge important contributions to this study made by the entire NCGENES 2 team, the High-Throughput Sequencing Facility at UNC, the Renaissance Computing Institute, the Mission Fullerton Genetics Lab, the Carolina Data Warehouse for Health, and the North Carolina Translational and Clinical Sciences Institute. We want to acknowledge the UNC BioSpecimen Processing Facility ( https://genome.unc.edu/bsp ) and the UNC Health Molecular Genetics Laboratory for our DNA extractions, blood processing, storage, and sample disbursement.
Funding Information:
The NCGENES 2 study is led by researchers at the University of North Carolina at Chapel Hill, one of six sites participating in the CSER 2 consortium, which is a national multi-site research program jointly funded by the National Human Genome Research Institute (NHGRI), the National Cancer Institute (NCI), and the National Institute on Minority Health and Health Disparities (NIMHD). The CSER 2 consortium sites and a coordinating center use interdisciplinary, translational research to evaluate the integration of GS into the clinical care of diverse and medically underserved individuals with suspected genetic disorders by developing and sharing best practices in areas such as informed consent, informed and shared decision making, patient-reported outcomes, and return of results.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - Background: Exome sequencing (ES) has probable utility for shortening the diagnostic odyssey of children with suspected genetic disorders. This report describes the design and methods of a study evaluating the potential of ES as a routine clinical tool for pediatric patients who have suspected genetic conditions and who are in the early stages of the diagnostic odyssey. Methods: The North Carolina Clinical Genomic Evaluation by Next-generation Exome Sequencing (NCGENES) 2 study is an interdisciplinary, multi-site Phase III randomized controlled trial of two interventions: educational pre-visit preparation (PVP) and offer of first-line ES. In this full-factorial design, parent-child dyads are randomly assigned to one of four study arms (PVP + usual care, ES + usual care, PVP + ES + usual care, or usual care alone) in equal proportions. Participants are recruited from Pediatric Genetics or Neurology outpatient clinics in three North Carolina healthcare facilities. Eligible pediatric participants are < 16 years old and have a first visit to a participating clinic, a suspected genetic condition, and an eligible parent/guardian to attend the clinic visit and complete study measures. The study oversamples participants from underserved and under-represented populations. Participants assigned to the PVP arms receive an educational booklet and question prompt list before clinical interactions. Randomization to offer of first-line ES is revealed after a child’s clinic visit. Parents complete measures at baseline, pre-clinic, post-clinic, and two follow-up timepoints. Study clinicians provide phenotypic data and complete measures after the clinic visit and after returning results. Reportable study-related research ES results are confirmed in a CLIA-certified clinical laboratory. Results are disclosed to the parent by the clinical team. A community consultation team contributed to the development of study materials and study implementation methods and remains engaged in the project. Discussion: NCGENES 2 will contribute valuable knowledge concerning technical, clinical, psychosocial, and health economic issues associated with using early diagnostic ES to shorten the diagnostic odyssey of pediatric patients with likely genetic conditions. Results will inform efforts to engage diverse populations in genomic medicine research and generate evidence that can inform policy, practice, and future research related to the utility of first-line diagnostic ES in health care. Trial registration: ClinicalTrials.govNCT03548779. Registered on June 07, 2018.
AB - Background: Exome sequencing (ES) has probable utility for shortening the diagnostic odyssey of children with suspected genetic disorders. This report describes the design and methods of a study evaluating the potential of ES as a routine clinical tool for pediatric patients who have suspected genetic conditions and who are in the early stages of the diagnostic odyssey. Methods: The North Carolina Clinical Genomic Evaluation by Next-generation Exome Sequencing (NCGENES) 2 study is an interdisciplinary, multi-site Phase III randomized controlled trial of two interventions: educational pre-visit preparation (PVP) and offer of first-line ES. In this full-factorial design, parent-child dyads are randomly assigned to one of four study arms (PVP + usual care, ES + usual care, PVP + ES + usual care, or usual care alone) in equal proportions. Participants are recruited from Pediatric Genetics or Neurology outpatient clinics in three North Carolina healthcare facilities. Eligible pediatric participants are < 16 years old and have a first visit to a participating clinic, a suspected genetic condition, and an eligible parent/guardian to attend the clinic visit and complete study measures. The study oversamples participants from underserved and under-represented populations. Participants assigned to the PVP arms receive an educational booklet and question prompt list before clinical interactions. Randomization to offer of first-line ES is revealed after a child’s clinic visit. Parents complete measures at baseline, pre-clinic, post-clinic, and two follow-up timepoints. Study clinicians provide phenotypic data and complete measures after the clinic visit and after returning results. Reportable study-related research ES results are confirmed in a CLIA-certified clinical laboratory. Results are disclosed to the parent by the clinical team. A community consultation team contributed to the development of study materials and study implementation methods and remains engaged in the project. Discussion: NCGENES 2 will contribute valuable knowledge concerning technical, clinical, psychosocial, and health economic issues associated with using early diagnostic ES to shorten the diagnostic odyssey of pediatric patients with likely genetic conditions. Results will inform efforts to engage diverse populations in genomic medicine research and generate evidence that can inform policy, practice, and future research related to the utility of first-line diagnostic ES in health care. Trial registration: ClinicalTrials.govNCT03548779. Registered on June 07, 2018.
KW - Clinical trial
KW - Community engagement
KW - Diagnostic odyssey
KW - ELSI
KW - Genetic disease
KW - Patient education
KW - Precision medicine
KW - Question prompt list
KW - Sequencing
KW - Under-represented populations
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UR - http://www.scopus.com/inward/citedby.url?scp=85107876854&partnerID=8YFLogxK
U2 - 10.1186/s13063-021-05341-2
DO - 10.1186/s13063-021-05341-2
M3 - Article
C2 - 34127041
AN - SCOPUS:85107876854
VL - 22
JO - Trials
JF - Trials
SN - 1745-6215
IS - 1
M1 - 395
ER -