Trials / Completed

CompletedNCT03548779

North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2

Status: Completed
Phase: N/A
Study type: Interventional
Enrollment: 548 (actual)

Sponsor: University of North Carolina, Chapel Hill · Academic / Other
Sex: All
Age: 0 Years
Healthy volunteers: Not accepted

Summary

The "North Carolina Clinical Genomic Evaluation by Next-gen Exome Sequencing, 2 (NCGENES 2)" study is part of a larger consortium project investigating the clinical utility, or net benefit of an intervention on patient and family well-being as well as diagnostic efficacy, management planning, and medical outcomes. A clinical trial will be implemented to compare (1) first-line exome sequencing to usual care and (2) participant pre-visit preparation to no pre-visit preparation. The study will use a randomized controlled design, with 2x2 factorial design, coupled with patient-reported outcomes and comprehensive clinical data collection addressing key outcomes, to determine the net impact of diagnostic results and secondary findings.

Detailed description

The NCGENES 2 study is part of the "Clinical Sequencing Evidence-Generating Research (CSER2)" - Clinical Sites with Enhanced Diversity (U01), and brings together interdisciplinary experts from across North Carolina to address questions critical to the translation of genomic medicine to the care of patients with suspected genetic disorders. In this renewal of the initial NCGENES study, NCGENES 2 will carry out a clinical trial of exome sequencing as a diagnostic test to answer the next set of questions vital to making genome-scale sequencing a routine clinical tool. The study population will be drawn from a state-wide network of Clinical Genetics and Pediatric Neurology clinics -- clinical domains in which patients are enriched for phenotypes caused by heterogeneous genetic conditions. Exome sequencing and genome sequencing (ES/GS) are efficient means of establishing a molecular diagnosis in these populations, with yields of positive or possible diagnostic results in at least 30% of patients examined based on findings from NCGENES and other work. Evidence will be generated regarding the clinical utility of ES/GS using a prospective randomized controlled trial that compares usual care plus exome sequencing to usual care. Patient-reported data, electronic health records data, and administrative claims data will be used to evaluate defined health outcomes, in collaboration with experts in health economics and health services research, to address pressing questions about the utility of exome sequencing. Furthermore, an examination of communication between patients and physicians, and between physicians and laboratories, and how these critical interactions affect the utility of genomic sequencing will be conducted. A second, nested randomized trial (crossed with exome sequencing in a full-factorial design) will be incorporated to test the hypothesis that a theory-based, multi-component pre-clinic preparation intervention for patients will improve patient-centered outcomes. An "embedded Ethical, Legal, and Social Implications (ELSI)" component will provide feedback to providers regarding communication discrepancies to iteratively improve care. Finally, the challenges of integrating clinical data and genomic information across a state-wide network of sites and examining different models of interaction between genomic clinicians and molecular diagnostic laboratorians will be explored.

Conditions

Interventions

Type	Name	Description
BEHAVIORAL	Pre-visit prep	Patient and provider surveys will be used to measure the impact of pre-visit preparation on the primary outcomes of engagement of participants in the clinical interaction and their view of the interaction as patient-centered, in addition to secondary outcomes that may be affected by this intervention (described above). The study investigators will test the hypothesis that patients will benefit from pre-visit preparation by: (1) rating their clinical encounters as more patient-centered and (2) asking more questions during their clinical encounters.
DIAGNOSTIC_TEST	usual care + exome seq	Provider surveys will be used to assess impact of exome sequencing on diagnostic thinking and management planning. Health utilization and condition-specific general clinical outcomes will be assessed from health records data.

Timeline

Start date: 2018-09-28
Primary completion: 2023-09-08
Completion: 2024-09-08
First posted: 2018-06-07
Last updated: 2025-05-13
Results posted: 2025-05-13

Locations

3 sites across 1 country: United States

Regulatory

FDA-regulated device study

Source: ClinicalTrials.gov record NCT03548779. Inclusion in this directory is not an endorsement.