Clinical Decision Support to Identify Pediatric Patients With Undiagnosed Genetic Disease

NCT06744543 | Active Not Recruiting

• 1 other identifier: 241678
• Study Type: interventional
• Target: 1,000
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Genetic Disease; Pediatrics; Predictive Model; Clinical Decision Support

Outcome Measures

Primary Outcomes (1)

• Number of Diagnoses in the intervention arm compared to the control arm

  Number of patients diagnosed via a Chromosomal Microarray.

  2 years

Secondary Outcomes (4)

• Time to test

  2 years

• Abnormal CMA

  2 years

• Rate of genetic testing

  2 years

• Diagnosis via any test (molecular confirmation)

  2 years

Study Arms (2)

Intervention

EXPERIMENTAL

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

Comparator

NO INTERVENTION

All remaining patients will be the comparator arm which will be standard of care as to avoid ethical situations of withholding potentially important care.

Interventions

SIGHT Prompted Provider Message DEVICE

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.

Intervention

Eligibility Criteria

• Age: 1 Year - 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University Medical

Nashville, Tennessee, 37232, United States

Location

Related Publications (1)

• 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.

  PMID: 34083811 BACKGROUND

MeSH Terms

Conditions

Genetic Diseases, Inborn

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Douglas Ruderfer, PhD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: There will be no blinding of participants or physicians as patients and providers will follow standard of care. Providers may dismiss the SIGHT - prompted provider message and not act on its recommendations at any time. No other intervention is planned. Patients would be unaware of the providers' decisions in that case unless the provider chooses independently to discuss the SIGHT score with them. A sample size re-estimation will be conducted after 250 patients have been randomized to account for uncertainty in the initial test-referral rate used in the sample size calculation. An independent analyst, who will be blinded to the randomization assignment, will calculate the observed test-referral rate across all patients.
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Model Details: 1:1 allocation by predicted probability to either the intervention group, receiving a SIGHT-prompted provider message, or the control group, receiving standard care without the SIGHT-prompted message. The randomization process will be integrated into the routine clinical workflow, with SIGHT scores generated before regularly scheduled patient visits in pediatric primary care at VUMC.

Study Record Dates

• First Submitted: December 16, 2024
• First Posted: December 20, 2024
• Study Start: March 12, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): February 1, 2027
• Last Updated: September 24, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)