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: a randomized controlled trial

Trials

Feng-Chang Lin¹  Jeannette T. Bensen²  Brooke S. Staley²  Jonathan S. Berg³  Bradford C. Powell³  Laura V. Milko³  Lonna Mollison³  Alicia Brandt³  Ann Katherine M. Foreman³  Julianne M. O’Daniel³  Tamara S. Roman³  Tracey L. Grant³  Angelo Navas³  Myra Roche⁴  Ida Griesemer⁵  Alexandra Lightfoot⁶  Christine Rini⁷  Suzanne C. O’Neill⁸  Margaret Waltz⁹  Laura Farnan^1,10 

[1] Department of Biostatistics, University of North Carolina at Chapel Hill, 27599, Chapel Hill, NC, USA;Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Campus Box #7295, 27599-7295, Chapel Hill, NC, USA;Department of Genetics, University of North Carolina at Chapel Hill, 27599, Chapel Hill, NC, USA;Department of Genetics, University of North Carolina at Chapel Hill, 27599, Chapel Hill, NC, USA;Department of Pediatrics, University of North Carolina at Chapel Hill School of Medicine, 27599, Chapel Hill, NC, USA;Department of Heath Behavior, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, 27599, Chapel Hill, NC, USA;Cecil G. Sheps Center for Health Services Research, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA;Department of Heath Behavior, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, 27599, Chapel Hill, NC, USA;Center for Health Promotion and Disease Prevention, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA;Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA;Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA;Department of Oncology, Georgetown University, 20007, Washington, DC, USA;Department of Social Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA;Lineberger Comprehensive Cancer Center, University of North Carolina, 27599, Chapel Hill, NC, USA;

关键词: Precision medicine;    Sequencing;    Under-represented populations;    Clinical trial;    Genetic disease;    Diagnostic odyssey;    Community engagement;    Patient education;    Question prompt list;    ELSI;   

DOI  :  10.1186/s13063-021-05341-2

来源: Springer

【 摘 要 】

BackgroundExome 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.MethodsThe 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.DiscussionNCGENES 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 registrationClinicalTrials.govNCT03548779. Registered on June 07, 2018.

【 授权许可】

CC BY