The NYCKidSeq project: study protocol for a randomized controlled trial incorporating genomics into the clinical care of diverse New York City children

Abstract

ABSTRACTBackgroundIncreasingly, genomics is informing clinical practice, but challenges remain for medical professionals lacking genetics expertise, and in access to and clinical utility of genomic testing for minority and underrepresented populations. The latter is a particularly pernicious problem due to the historical lack of inclusion of racially and ethnically diverse populations in genomic research and genomic medicine. A further challenge is the rapidly changing landscape of genetic tests, and considerations of cost, interpretation and diagnostic yield for emerging modalities like whole genome sequencing.MethodsThe NYCKidSeq project is a randomized controlled trial recruiting 1,130 children and young adults predominantly from Harlem and the Bronx with suspected genetic disorders in three disease categories: neurologic, cardiovascular, and immunologic. Two clinical genetic tests will be performed for each participant, either proband, duo or trio whole-genome sequencing (depending on sample availability) and proband targeted gene panels. Clinical utility, cost and diagnostic yield of both testing modalities will be assessed. This study will evaluate the use of a novel, digital platform (GUÍA) to digitize the return of genomic results experience and improve participant understanding for English- and Spanish-speaking families. Surveys will collect data at three study visits; baseline (0 months), results disclosure visit (ROR1, +3 months), and follow up visit (ROR2, +9 months). Outcomes will assess parental understanding of and attitudes towards receiving genomic results for their child and behavioral, psychological and social impact of results. We will also conduct a pilot study to assess a digital tool called GenomeDiver designed to enhance communication between clinicians and genetic testing labs. We will evaluate GenomeDiver’s ability to increase the diagnostic yield compared to standard practices, to improve clinician’s ability to perform targeted reverse phenotyping, and to increase the efficiency of genetic testing lab personnel.DiscussionThe NYCKidSeq project will contribute to the innovations and best practices in communicating genomic test results to diverse populations. This work will inform strategies for implementing genomic medicine in health systems serving diverse populations using methods that are clinically useful, technologically savvy, culturally sensitive, and ethically sound.