Clinical Decision Support to Identify Pediatric Patients With Undiagnosed Genetic Disease (SIGHT)

Randomized Controlled Trial to Assess EHR Prediction Model to Identify Pediatric Patients With Undiagnosed Genetic Disease"

This study will evaluate the effectiveness of SIGHT as a clinical support system to prompt provider/patient discussion and shared decision making regarding the need for genetic testing in the form of a chromosomal microarray. Identifying patients at high predicted probability of needing a test in clinical settings will be examined to determine if it decreases the duration of time to testing and increases diagnostic yield. SIGHT requires only data already collected in routine clinical encounters and is calculated prior to a clinical visit at VUMC.

Study Overview

• Status: Active, not recruiting
• Conditions: Genetic Disease; Pediatrics; Predictive Model; Clinical Decision Support
• Intervention / Treatment: Device: SIGHT Prompted Provider Message

• Study Type: Interventional
• Enrollment (Estimated): 1000
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• All patients > 1 year old, < 20 years of age with a scheduled visit to the VUMC pediatric primary care.

Exclusion Criteria:

• Patients who have been programmatically excluded due to having already received a chromosomal microarray at VUMC and patients > 20 years of age or < 1 year of age.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; SIGHT predictions will be generated prior to a scheduled encounter in one of the participating study clinics. Patients with a SIGHT probability above a predefined risk level (0.30 predicted risk based on validation and prior chart review by a genetic counselor, Morley et al, 2021 below) will prompt randomization to the standard care or SIGHT-guided intervention arm. For patients randomized to the SIGHT-guided intervention arm, the clinician responsible for care in that encounter (determined in the usual course of care) will receive a message for that patient and details as to the contributing clinical features that led to the high probability. The message will include a recommendation, but providers will have full discretion to offer genetic testing or refer to genetics providers. The management of screening will follow standard of care at VUMC.	Device: SIGHT Prompted Provider Message; Among patients surpassing a 0.30 probability threshold that have a scheduled visit to pediatric primary care at VUMC, 500 will be randomized to the intervention and a SIGHT-prompted provider message will be generated.
No Intervention: Comparator; All remaining patients will be the comparator arm which will be standard of care as to avoid ethical situations of withholding potentially important care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Diagnoses in the intervention arm compared to the control arm	Number of patients diagnosed via a Chromosomal Microarray.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to test	Duration of time to genetic testing. Time to event, measured from the initial patient visit to the time genetic testing is conducted.	2 years
Abnormal CMA	Number of patients flagged by SIGHT who's CMA result returned abnormal but in the absence of diagnostic findings.	2 years
Rate of genetic testing	Rates of genetic testing ordered by providers after a pediatric visit.	2 years
Diagnosis via any test (molecular confirmation)	Number of patients flagged by SIGHT who receive a diagnosis via any molecular test.	2 years

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Investigators: Principal Investigator: Douglas Ruderfer, PhD, Vanderbilt University Medical Center

Publications and helpful links

General Publications

• Morley TJ, Han L, Castro VM, Morra J, Perlis RH, Cox NJ, Bastarache L, Ruderfer DM. Phenotypic signatures in clinical data enable systematic identification of patients for genetic testing. Nat Med. 2021 Jun;27(6):1097-1104. doi: 10.1038/s41591-021-01356-z. Epub 2021 Jun 3.

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: December 16, 2024
• First Submitted That Met QC Criteria: December 16, 2024
• First Posted (Actual): December 20, 2024

Study Record Updates

• Last Update Posted (Estimated): September 24, 2025
• Last Update Submitted That Met QC Criteria: September 23, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn
• Other Study ID Numbers: 241678

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Patients in this study will receive standard of care at Vanderbilt University Medical Center (VUMC) and will not be consented for research participation. As a result, no individual participant data (IPD) will be made available for sharing with other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No