Genomic Medicine for Ill Neonates and Infants (The GEMINI Study)

Study Overview
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Brief Summary
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The Genomic Medicine for Ill Neonates and Infants (The GEMINI Study) is a research study aimed at comparing the clinical and economic utility of performing rapid whole genomic sequencing versus a targeted genomic sequencing panel on neonates and infants suspected of having a genetic disorder. This study is funded by the National Institutes of Health. This multicenter, prospective clinical trial will enroll 400 subjects at the Floating Hospital for Children at Tufts Medical Center (Boston, MA), Cincinnati Children's Hospital Medical Center (Cincinnati, OH), Mount Sinai Kravis Children's Hospital (New York, NY), North Carolina Children's Hospital (Chapel Hill, NC), Children's Hospital of Pittsburgh (Pittsburgh, PA), and Rady Children's Hospital (San Diego, CA).

Detailed Description
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This multicenter, prospective clinical trial will examine the diagnostic yield and clinical utility of NewbornDx, a targeted genomic sequencing panel for use in the neonate, and rapid whole genomic sequencing (rWGS) testing in high-risk infants with signs/symptoms consistent with a possible genetic disorder. Infants will undergo NewbornDx and rWGS (proband) testing. The biological parent(s), when available, will undergo NewbornDx testing at the same time as the infant. For rWGS,the infant will undergo testing first. If a specific diagnosis that is consistent with the phenotype is not made with rWGS proband analysis alone, the parent(s) will undergo rWGS. The study will also evaluate the cost effectiveness of each test as well as standard of care (SOC) testing. A retrospective chart review of infants with suspected genetic disorders will be done to understand 1-year cost and health outcomes that would have been incurred in the absence of the advanced testing. The resulting data from the trial will be used in the economic evaluation comparing NewbornDx, rWGS, and SOC over a 1-year period and used as basis to simulate the lifetime cost-effectiveness of these testing strategies. A web-based clinical reference database to provide references, clinical management guidelines, opportunities for clinical trial participation, and support groups for each condition will be developed with separate interfaces for the parent/guardian(s) and medical provider. The clinical reference database will be qualitatively assessed by a survey of medical providers.

Official Title
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Genomic Medicine for Ill Neonates and Infants (The GEMINI Study)

Conditions
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Pediatric: Genetic Syndrome

Intervention / Treatment
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* Diagnostic Test: rapid whole genomic sequencing (rWGS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented informed consent from the parent/guardian Signs/symptoms consistent with a possible genetic disorder Admitted to a hospital participating in this study at the time of enrollment Less than one year corrected gestational age Exclusion Criteria: A known genetic diagnosis (e.g. prenatal testing) Major congenital anomaly associated with a chromosomal anomaly detected on prenatal testing Presence of documented congenital infection Infants considered non-viable due to prematurity (< 23 0/7 weeks GA)

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 1 Year

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: rapid whole genomic sequencing (rWGS)|rWGS and NewbornDx are genomic sequencing platforms|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of subjects with a confirmed genetic disorder detected by NewbornDx | If NewbornDx diagnoses a genetic disorder | 1-2 weeks | 
| The number of subjects with a confirmed genetic disorder detected by rWGS | If rWGS diagnoses a genetic disorder | 1-2 weeks | 
| Time in hours to a positive result by NewbornDx | Duration of time (hours) to determine diagnosis by NewbornDx | 1-2 weeks | 
| Time in hours to a positive result by rWGS | Duration of time (hours) to determine diagnosis by rWGS | 1-2 weeks | 
| Perception of the clinical utility of genomic sequencing | The Clinician Assessment of Clinical Utility assessed by physician survey using units on a likert scale with 1 meaning not useful at all and 5 meaning very useful | 1 week | 
| Clinical utility of genomic sequencing as assessed by changes in clinical care management | The Clinician Assessment of Clinical Utility assessed by physician survey selecting the specific types of 35 possible management changes (i.e. surgical intervention implemented, medication changed, etc.) | 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| One year cost-effectiveness of standard of care (SOC), NewbornDx and rWGS testing | All three care platforms will be assessed for their cost-effectiveness based on Quality-Adjusted-Life Year. Qualities are assessed on a scale ranging from 0 (deceased) to 1 (perfect health). | 5 years | 
| Lifetime cost-effectiveness of SOC, NewbornDx and rWGS testing | All three care platforms will be assessed for their cost-effectiveness based on Quality-Adjusted-Life Year. Qualities are assessed on a scale ranging from 0 (deceased) to 1 (perfect health). | 5 years | 
| User satisfaction with the clinical reference database providing physician-specific information about treatments, resources and ongoing clinical trials regarding the genetic disorder diagnosed: likert scale | The Clinician Satisfaction with Return of Genomic Testing Information survey assessed by physicians using units on a likert scale with 1 meaning not useful at all and 5 meaning very useful | 5 years |