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

Abstract

Background: Increasingly, 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.

Methods: The NYCKidSeq project is a randomized controlled trial recruiting 1130 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), result disclosure visit (ROR1, + 3 months), and follow-up visit (ROR2, + 9 months). Outcomes will assess parental understanding of and attitudes toward 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, improve clinician's ability to perform targeted reverse phenotyping, and increase the efficiency of genetic testing lab personnel.

Discussion: The 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.

Trial registration: ClinicalTrials.gov NCT03738098 . Registered on November 13, 2018 Trial Sponsor: Icahn School of Medicine at Mount Sinai Contact Name: Eimear Kenny, PhD (Principal Investigator) Address: Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Pl., Box 1003, New York, NY 10029 Email: eimear.kenny@mssm.edu.

Keywords: Clinical utility; Genomic sequencing; Healthcare utilization; Pediatric genetics; Return of results; Underrepresented populations; Whole-genome sequencing.

Fig. 1

NYCKidSeq study design. The NYCKidSeq study involves two phases, a lead-in phase and a randomized controlled trial (RCT). Participants in both phases receive TGP and WGS testing and complete surveys at baseline, after result disclosure (ROR1 survey), and 6 months after result disclosure (ROR2 survey). In the lead-in phase, participants (N = 30) are enrolled into either the GUÍA feedback arm where participants complete a structured feedback interview after completion of the ROR1 survey or survey feedback arm where participants provide survey feedback after completing each survey. In the RCT phase, participants (N = 1100) are randomized to the GUÍA arm or the standard of care arm (SOC). Participants in the GUÍA arm receive result disclosure from genetic counselors using GUÍA versus participants in the SOC arm who receive SOC genetic counseling

Fig. 2

Randomization schema