Trial Outcomes & Findings for Clinical Utility of Pediatric Whole Exome Sequencing (NCT NCT03525431)

Last Updated: 2023-07-18

Results Overview

Number of pediatric patients with a diagnostic result among all patients where exome was performed. A positive exome sequencing result means the identification of a pathogenic or likely pathogenic gene variant to explain the child's condition. The definition of pediatric was expanded to include participants over the age of 18 if they were being followed by UCSF pediatrics department if they were patients at the pediatrics department before they were 18 years old.

Recruitment status

COMPLETED

Study phase

Target enrollment

529 participants

Primary outcome timeframe

At the completion of data collection (follow-up visit at 6-12 months after return of results)

Results posted on

2023-07-18

Participant Flow

We recruited pediatric patients to this study. We aimed to reach 800 pediatric cases in the beginning of the study, and we completed 529 cases at the end.

This is an exploratory study to define the diagnostic yield of exome sequencing in this pediatric population. All participants were offered the same test and received the same study procedures. There are no arms in this study.

Participant milestones

Participant milestones
Measure	Whole Exome Sequencing Following consent and collection of standardized phenotypic data, probands and biological parents will undergo WES with variant analysis conducted utilizing primary gene lists based on referring clinical indication. After results provision and follow up 6-12 months later, clinical utility will be assessed in those with a positive result (pathogenic or likely pathogenic variant) and those with negative results (no variant returned or a VUS) using specific outcomes at each site to examine effectiveness for both the child and family. Whole Exome Sequencing: Whole Exome Sequencing is a form of Next Generation Sequencing allowing investigators to assess the coding regions of many thousands of genes to find variants implicated in disease.
Overall Study STARTED	529
Overall Study COMPLETED	529
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Clinical Utility of Pediatric Whole Exome Sequencing

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Whole Exome Sequencing n=529 Participants Following consent and collection of standardized phenotypic data, probands and biological parents will undergo WES with variant analysis conducted utilizing primary gene lists based on referring clinical indication. After results provision and follow up 6 months later, diagnostic yield will be assessed as a measure of clinical utility. Those with a positive result (pathogenic or likely pathogenic variant) divided by the total number of cases sequenced will give the diagnostic yield. The assessment will be per pediatric case (proband), meaning, genomic data from biological parents and occasionally from siblings will be used to support the diagnosis for the proband. Whole Exome Sequencing: Whole Exome Sequencing is a form of Next Generation Sequencing allowing investigators to assess the coding regions of many thousands of genes to find variants implicated in disease.
Age, Categorical <=18 years	525 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=93 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants
Age, Continuous	5.0 Years n=93 Participants
Sex: Female, Male Female	239 Participants n=93 Participants
Sex: Female, Male Male	290 Participants n=93 Participants
Race/Ethnicity, Customized American Indian, Native American, Alaska Native	5 Participants n=93 Participants
Race/Ethnicity, Customized Asian	45 Participants n=93 Participants
Race/Ethnicity, Customized Black/African American	19 Participants n=93 Participants
Race/Ethnicity, Customized Native Hawaiian, Pacific Islander	5 Participants n=93 Participants
Race/Ethnicity, Customized White/European American	99 Participants n=93 Participants
Race/Ethnicity, Customized Middle Eastern/North African	22 Participants n=93 Participants
Race/Ethnicity, Customized Hispanic/Latino(a)	226 Participants n=93 Participants
Race/Ethnicity, Customized More than one	40 Participants n=93 Participants
Race/Ethnicity, Customized Unknown/none of these fully describe me	68 Participants n=93 Participants
Region of Enrollment United States	529 participants n=93 Participants

PRIMARY outcome

Timeframe: At the completion of data collection (follow-up visit at 6-12 months after return of results)

Population: 529 Probands total were enrolled in the study, 525 pediatric participants, and 4 were over the age of 18.

Outcome measures

Outcome measures
Measure	Whole Exome Sequencing n=529 Participants Following consent and collection of standardized phenotypic data, probands and biological parents will undergo WES with variant analysis conducted utilizing primary gene lists based on referring clinical indication. After results provision and follow up 6-12 months later, clinical utility will be assessed in those with a positive result (pathogenic or likely pathogenic variant) and those with negative results (no variant returned or a VUS) using specific outcomes at each site to examine effectiveness for both the child and family. Whole Exome Sequencing: Whole Exome Sequencing is a form of Next Generation Sequencing allowing investigators to assess the coding regions of many thousands of genes to find variants implicated in disease.
Number of Pediatric Patients With a Positive Exome Sequencing Result	142 Participants

Adverse Events

Whole Exome Sequencing

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Mary Norton

University of California, San Francisco

Phone: (415) 476 4080

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place