North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2 (NCGENES2)

• ClinicalTrials.gov Identifier: NCT03548779
• Recruitment Status: Active, not recruiting
• First Posted: June 7, 2018
• Last Update Posted: December 16, 2021
• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: National Human Genome Research Institute (NHGRI); East Carolina University; Mission Health System, Asheville, NC
• Information provided by (Responsible Party): University of North Carolina, Chapel Hill

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Epilepsy; Seizure; Neuromuscular Diseases; Brain Malformation; Intellectual Disability; Autism Spectrum Disorder; Hypotonia; Inborn Errors of Metabolism; Movement Disorders; Genetic Disease; Development Delay; Chromosome Abnormality; Hearing Loss; Dysmorphic Features; Skeletal Dysplasia; Congenital Abnormality; Microcephaly; Macrocephaly	Behavioral: Pre-visit prep; Diagnostic Test: usual care + exome seq	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 806 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Care Provider, Outcomes Assessor)

Masking Description

The study coordinator will assign the first randomization to pre-visit preparation arm and care providers will not be told of the patient's pre-visit preparatory randomization arm prior to the first usual care visit. Randomization to exome sequencing will be performed after the first usual care visit by the study coordinator.

Investigators will receive de-identified coded data and thus will not be able to link a patient name to an intervention arm. Some analyses will require individual-level randomization arm status to allow for comparison of parent questionnaire responses or health outcomes by arm - a major focus of this study.

All interviewers and medical records staff conducting telephone surveys and/or medical records abstraction for clinical data will be blinded to the participants randomization status. Access to this information will be blocked in the electronic patient tracking status by study role.

• Primary Purpose: Diagnostic
• Official Title: North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2
• Actual Study Start Date: September 28, 2018
• Estimated Primary Completion Date: May 2023
• Estimated Study Completion Date: May 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Pre-visit prep / usual care + exome seq; Participants randomized to pre-visit prep will receive a study packet with educational materials and a question prompt list. These participants will be instructed to review the materials, discuss them with family members if desired, use the question prompt list to select questions they would like to ask at clinic visit 1, and bring the list to their clinic visit 1 appointment. Participants will receive usual care and will be offered research exome sequencing.	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.
Experimental: Pre-visit prep / usual care; Participants randomized to pre-visit prep will receive a study packet with educational materials and a question prompt list. These participants will be instructed to review the materials, discuss them with family members if desired, use the question prompt list to select questions they would like to ask at clinic visit 1, and bring the list to their clinic visit 1 appointment. Participants will receive usual care.	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.
Experimental: No prep / usual care + exome seq; Participants in the no pre-visit preparation arm will receive a mailed card reminding them about their upcoming clinic visit. Participants will receive usual care and will be offered research exome sequencing.	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.
No Intervention: No prep / usual care; Participants in the no pre-visit preparation arm will receive a mailed card reminding them about their upcoming clinic visit. Participants will receive usual care.

Outcome Measures

Primary Outcome Measures :

1. Number of in-patient hospital admissions 1 year prior to return of results [ Time Frame: 1 year prior to return of results ]
   Count of number of in-patient hospital admissions during 1 year prior to return of results using data obtained from the Electronic Medical Record. Coded by trained study staff.
2. Number of in-patient hospital admissions 1 year after return of results [ Time Frame: 1 year after return of results ]
   Count of number of in-patient hospital admissions during 1 year after return of results using data obtained from the Electronic Medical Record. Coded by trained study staff.
3. Number of in-patient hospital days 1 year prior to return of results [ Time Frame: 1 year prior to return of results ]
   Count of number of in-patient hospital days during 1 year prior to return of results using data obtained from the Electronic Medical Record. Coded by trained study staff.
4. Number of in-patient hospital days 1 year after return of results [ Time Frame: 1 year after return of results ]
   Count of number of in-patient hospital days during 1 year after return of results using data obtained from the Electronic Medical Record. Coded by trained study staff.
5. Number of long-term care admissions 1 year prior to return of results [ Time Frame: 1 year prior to return of results ]
   Count of number of long-term care admissions during 1 year prior to return of results using data obtained from the Electronic Medical Record. Coded by trained study staff.
6. Number of long-term care admissions 1 year after return of results [ Time Frame: 1 year after return of results ]
   Count of number of long-term care admissions during 1 year after return of results using data obtained from the Electronic Medical Record. Coded by trained study staff.
7. Number of long-term care days 1 year prior to return of results [ Time Frame: 1 year prior to return of results ]
   Count of number of long-term care days during 1 year prior to return of results using data obtained from the Electronic Medical Record. Coded by trained study staff.
8. Number of long-term care days 1 year after return of results [ Time Frame: 1 year after return of results ]
   Count of number of long-term care days during 1 year after return of results using data obtained from the Electronic Medical Record. Coded by trained study staff.
9. Number of ER visits 1 year prior to return of results [ Time Frame: 1 year prior to return of results ]
   Count of number of ER visits during 1 year prior to return of results using data obtained from the Electronic Medical Record. Coded by trained study staff.
10. Number of ER visits 1 year after return of results [ Time Frame: 1 year after return of results ]
    Count of number of ER visits during 1 year after return of results using data obtained from the Electronic Medical Record. Coded by trained study staff.
11. Number of specialists visits 1 year prior to return of results [ Time Frame: 1 year prior to return of results ]
    Count of number of specialists visits during 1 year prior to return of results using data obtained from the Electronic Medical Record. Coded by trained study staff.
12. Number of specialists visits 1 year after return of results [ Time Frame: 1 year after return of results ]
    Count of number of specialists visits during 1 year after return of results using data obtained from the Electronic Medical Record. Coded by trained study staff.
13. Initial Patient Pediatric Quality of Life (Peds QL) score [ Time Frame: 4-6 weeks prior to clinic visit 1 ]
    The Peds QL Measurement Model for the Pediatric Quality of Inventory measures the core dimensions of health as delineated by the World Health Organization as well as role (school) functioning. The 23-item PedsQL Core Scales (Physical Functioning, Emotional Functioning, Social Functioning, and School Functioning) are developmentally appropriate surveys (Ages 2-4, 5-7, 8-12, 13-18) designed for parent proxy report. The 23 items are grouped together on the questionnaire, and are answered on a scale of 0-4. Items are reversed scored and linearly transformed to a 0-100 scale (0=100, 1=75, 2=50, 3=25, 4=0), so that higher scores indicate better Health-Related Quality of Life (HRQOL). This questionnaire will be self-administered at home.
14. Intermediate Patient Pediatric Quality of Life (Peds QL) score [ Time Frame: 2 weeks after return of results ]
    The Peds QL Measurement Model for the Pediatric Quality of Inventory measures the core dimensions of health as delineated by the World Health Organization as well as role (school) functioning. The 23-item PedsQL Core Scales (Physical Functioning, Emotional Functioning, Social Functioning, and School Functioning) are developmentally appropriate surveys (Ages 2-4, 5-7, 8-12, 13-18) designed for parent proxy report. The 23 items are grouped together on the questionnaire, and are answered on a scale of 0-4. Items are reversed scored and linearly transformed to a 0-100 scale (0=100, 1=75, 2=50, 3=25, 4=0), so that higher scores indicate better HRQOL. This questionnaire will be interviewer-administered by telephone.
15. Final Patient Pediatric Quality of Life (Peds QL) score [ Time Frame: 6 months after return of results ]
    The Peds QL Measurement Model for the Pediatric Quality of Inventory measures the core dimensions of health as delineated by the World Health Organization as well as role (school) functioning. The 23-item PedsQL Core Scales (Physical Functioning, Emotional Functioning, Social Functioning, and School Functioning) are developmentally appropriate surveys (Ages 2-4, 5-7, 8-12, 13-18) designed for parent proxy report. The 23 items are grouped together on the questionnaire, and are answered on a scale of 0-4. Items are reversed scored and linearly transformed to a 0-100 scale (0=100, 1=75, 2=50, 3=25, 4=0), so that higher scores indicate better HRQOL. This questionnaire will be interviewer administered by telephone.
16. Initial Caregiver QoL score [ Time Frame: 4-6 weeks prior to clinic visit 1 ]
    The Short-Form Health Survey (SF-12) questionnaire is a reliable measure of perceived health that describes the degree of general physical health status and mental health distress. It consists of 12 items, derived from the physical and mental domains. Scores have a range of 0 to 100 and were designed to have a mean score of 50 and a standard deviation of 10 in a representative sample of the US population, with higher scores indicating greater functioning. This questionnaire will be self-administered at home.
17. Intermediate Caregiver QoL score [ Time Frame: 2 weeks after return of results ]
    The SF-12 questionnaire is a reliable measure of perceived health that describes the degree of general physical health status and mental health distress. It consists of 12 items, derived from the physical and mental domains. Scores have a range of 0 to 100 and were designed to have a mean score of 50 and a standard deviation of 10 in a representative sample of the US population, with higher scores indicating greater functioning. This questionnaire will be interviewer administered by telephone.
18. Final Caregiver QoL score [ Time Frame: 6 months after return of results ]
    The SF-12 questionnaire is a reliable measure of perceived health that describes the degree of general physical health status and mental health distress. It consists of 12 items, derived from the physical and mental domains. Scores have a range of 0 to 100 and were designed to have a mean score of 50 and a standard deviation of 10 in a representative sample of the US population, with higher scores indicating greater functioning. This questionnaire will be interviewer administered by telephone.
19. Post-Clinic Visit 1 Mean Patient Centeredness Score [ Time Frame: Immediately after clinic 1 day of visit 1 ]
    Patient centeredness scale, which measures the caregiver's perception of the level of patient centeredness of their visit with their child's provider (developed by Little et al., 2001). Self-administered in the clinic, immediately after clinic visit 1. Item responses will be coded as: 1=Very strongly disagree; 2=Strongly disagree; 3=Moderately disagree; 4=Neither agree nor disagree; 5=Moderately agree; 6=Strongly agree; 7=Very strongly agree. Mean scores will be calculated by summing the response values and dividing by the total number of items (21). Higher scores indicate stronger perceptions of patient centeredness.
20. Post-Return of Results Mean Patient Centeredness Score [ Time Frame: 2 weeks after return of results ]
    Patient centeredness scale, which measures the caregiver's perception of the level of patient centeredness of their visit with their child's provider (developed by Little et al., 2001). Interviewer administered by telephone. Item responses will be coded as: 1=Very strongly disagree; 2=Strongly disagree; 3=Moderately disagree; 4=Neither agree nor disagree; 5=Moderately agree; 6=Strongly agree; 7=Very strongly agree. Mean scores will be calculated by summing the response values and dividing by the total number of items (21). Higher scores indicate stronger perceptions of patient centeredness.
21. Number of questions caregiver asks in Clinic Visit 1 [ Time Frame: During clinic 1 day of visit 1 ]
    Count of number of questions caregiver asks provider in the audio recording of clinic visit 1. Coded by trained study staff.

Secondary Outcome Measures :

1. Initial Average Peds QL score for "missing school for not feeling well" [ Time Frame: 4-6 weeks prior to clinic visit 1 ]
   This is a single item measure from the Peds QL that will be answered on a scale of 0-4. Items are reversed scored and linearly transformed to a 0-100 scale (0=100, 1=75, 2=50, 3=25, 4=0), so that higher scores indicate better HRQOL for this single measure. This questionnaire will be self-administered at home.
2. Intermediate Average Peds QL score for "missing school for not feeling well" [ Time Frame: 2 weeks after return of results ]

   This is a single item measure from the Peds QL that will be answered on a scale of 0-4. Items are reversed scored and linearly transformed to a 0-100 scale (0=100, 1=75, 2=50, 3=25, 4=0), so that higher scores indicate better HRQOL for this single measure. This questionnaire will be interviewer-administered by telephone.

   Edit on 3/18/21: this outcome will not be measured because of a protocol amendment to not include the PedsQL survey at 2-weeks post-RoR parent survey.

3. Final Average Peds QL score for "missing school for not feeling well" [ Time Frame: 6 months after return of results ]
   This is a single item measure from the Peds QL that will be answered on a scale of 0-4. Items are reversed scored and linearly transformed to a 0-100 scale (0=100, 1=75, 2=50, 3=25, 4=0), so that higher scores indicate better HRQOL for this single measure. This questionnaire will be interviewer-administered by telephone.
4. Initial Average Peds QL score for "missing school for doctors visit" [ Time Frame: 4-6 weeks prior to clinic visit 1 ]
   This is a single item measure from the Peds QL that will be answered on a scale of 0-4. Items are reversed scored and linearly transformed to a 0-100 scale (0=100, 1=75, 2=50, 3=25, 4=0), so that higher scores indicate better HRQOL for this single measure. This measure will be included in the questionnaire that will be self-administered at home.
5. Intermediate Average Peds QL score for "missing school for doctors visit" [ Time Frame: 2 weeks after return of results ]

   This is a single item measure from the Peds QL that will be answered on a scale of 0-4. Items are reversed scored and linearly transformed to a 0-100 scale (0=100, 1=75, 2=50, 3=25, 4=0), so that higher scores indicate better HRQOL for this single measure. This measure will be interviewer administered by telephone.

   Edit on 3/18/21: this outcome will not be measured because of a protocol amendment to not include the PedsQL survey at 2-weeks post-RoR parent survey.

6. Final Average Peds QL score for "missing school for doctors visit" [ Time Frame: 6 months after return of results ]
   This is a single item measure from the Peds QL that will be answered on a scale of 0-4. Items are reversed scored and linearly transformed to a 0-100 scale (0=100, 1=75, 2=50, 3=25, 4=0), so that higher scores indicate better HRQOL for this single measure. This measure will be interviewer administered by telephone.
7. Initial Amount of work missed because of child's condition or treatments score [ Time Frame: 4-6 weeks prior to clinic visit 1 ]
   This is a single item measure that will be answered on a scale of 1-6 where 1=None, 2=Less than a week, 3=Between 1 and 4 weeks, 4= Between 4 and 8 weeks, 5=Between 8 and 12 weeks, 6=I stopped working altogether. Higher scores indicate greater amounts of work missed because of the child's condition or treatments. This measure will be included in the questionnaire that will be self-administered at home.
8. Intermediate Amount of work missed because of child's condition or treatments score [ Time Frame: 2 weeks after return of results ]
   This is a single item measure that will be answered on a scale of 1-6 where 1=None, 2=Less than a week, 3=Between 1 and 4 weeks, 4= Between 4 and 8 weeks, 5=Between 8 and 12 weeks, 6=I stopped working altogether. Higher scores indicate greater amounts of work missed because of the child's condition or treatments. This measure will be interviewer-administered by telephone.
9. Final Amount of work missed because of child's condition or treatments score [ Time Frame: 6 months after return of results ]
   This is a single item measure that will be answered on a scale of 1-6 where 1=None, 2=Less than a week, 3=Between 1 and 4 weeks, 4= Between 4 and 8 weeks, 5=Between 8 and 12 weeks, 6=I stopped working altogether. Higher scores indicate greater amounts of work missed because of the child's condition or treatments. This measure will be interviewer-administered by telephone.
10. Initial Difficulty with finishing normal work (including both work outside of the home and housework) because of child's condition or treatments score [ Time Frame: 4-6 weeks prior to clinic visit 1 ]
    This is a single item measure that will be answered on a scale of 1-5, where 1=Not at all, 2=A little bit, 3=Somewhat, 4=Quite a bit, 5=Very much. Higher scores indicate greater difficulty finishing normal work (including both work outside of the home and housework) because of child's condition or treatments. This measure will be included in the questionnaire that will be self-administered at home.
11. Intermediate Difficulty with finishing normal work (including both work outside of the home and housework) because of child's condition or treatments score [ Time Frame: 2 weeks after return of results ]
    This is a single item measure that will be answered on a scale of 1-5, where 1=Not at all, 2=A little bit, 3=Somewhat, 4=Quite a bit, 5=Very much. Higher scores indicate greater difficulty finishing normal work (including both work outside of the home and housework) because of child's condition or treatments. This measure will be interviewer-administered by telephone.
12. Final Difficulty with finishing normal work (including both work outside of the home and housework) because of child's condition or treatments score [ Time Frame: 6 months after return of results ]
    This is a single item measure that will be answered on a scale of 1-5, where 1=Not at all, 2=A little bit, 3=Somewhat, 4=Quite a bit, 5=Very much. Higher scores indicate greater difficulty finishing normal work (including both work outside of the home and housework) because of child's condition or treatments. This measure will be interviewer-administered by telephone.
13. Vital status at final f/u [ Time Frame: final follow-up, up to approximately three years after clinic visit 1 ]
    Based on NC Vital Statistics, the child's vital status will be reported as living or deceased.
14. Child causes of death related to the primary condition [ Time Frame: final follow-up up to approximately three years after clinic visit 1 ]
    Based on NC Vital Statistics, child causes of death will be reported as related to the disorder of the child or not related to the disorder of the child.
15. Percent concordance of caregiver and provider reports of genetic or genomic test results [ Time Frame: 2 weeks after return of results ]
    Concordance between caregiver and provider reports of whether patients' diagnostic results were positive, negative, or uncertain. Coded as a dichotomous variable: 0=discordant diagnostic reports; 1=concordant diagnostic reports.
16. Mean Baseline Self Efficacy Score [ Time Frame: 4-6 weeks prior to clinic visit 1 ]
    Self-efficacy scale, which measures caregivers' confidence in communicating with their child's provider. Self-administered as part of the intake questionnaire. Measured with adapted Decision Self Efficacy Scale (developed by O'Connor, 1995). Adapted wording from the original scale so items refer to general communication, as opposed to a specific decision. Shorted scale to 7 items from 11 since not all items were applicable to this study. Item responses will be coded as: 1=Not at all confident; 5=Very confident. Mean scores will be calculated by summing the response values and dividing by the total number of items (7). Higher scores indicate higher confidence in communicating with their child's provider.
17. Mean Pre-Clinic Visit 1 Self Efficacy Score [ Time Frame: Immediately before Clinic Visit 1 ]
    Self-efficacy scale, which measures caregivers' confidence in communicating with their child's provider. Self-administered as part of the intake questionnaire. Measured with adapted Decision Self Efficacy Scale (developed by O'Connor, 1995). Adapted wording from the original scale so items refer to general communication, as opposed to a specific decision. Shorted scale to 7 items from 11 since not all items were applicable to this study. Item responses will be coded as: 1=Not at all confident; 5=Very confident. Mean scores will be calculated by summing the response values and dividing by the total number of items (7). Higher scores indicate higher confidence in communicating with their child's provider.
18. Post-Return of Results Mean FACToR Uncertainty Subscale Score [ Time Frame: 2 weeks after return of results ]
    Subscale of the Feeling About genomiC Testing Results measure assesses caregivers' level of uncertainty about their child's genetic test results (developed by Gallego et al., 2014). Interviewer administered by telephone. Item responses will be coded as: 1=Not at all; 2=A little; 3=Somewhat; 4=A good deal; 5=A great deal. Mean scores will be calculated by summing the response values and dividing by the total number of items (3). Higher scores indicate greater uncertainty about their child's genetic test results.

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Both children and parents are participants:

Inclusion Criteria:

Parents meeting the following criteria:

1. Parent of a child who meets the criteria below
2. At least 18 years old.
3. Must be able to provide informed consent for child and self.
4. Must be fluent in English or Spanish.

Children meeting the following criteria:

1. Infants and children 15 years old or less.
2. Referred for initial evaluation of a possible monogenic disorder OR
3. Seen for evaluation of an undiagnosed disorder in a study-associated clinic.

Exclusion Criteria:

Parents:

1. Younger than 18 years old.
2. Unwilling to complete study surveys and other procedures.
3. Have cognitive or other impairments precluding ability to provide giving informed consent.
4. Not fluent in English or Spanish.
5. Unable to attend all clinic visits

Children:

1. Have a known genetic or non-genetic diagnosis (only referred for counseling or management).
2. Medically unstable.

Contacts and Locations

Locations

United States, North Carolina

Mission Health

Asheville, North Carolina, United States, 28801

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States, 27599

East Carolina University

Greenville, North Carolina, United States, 27858

Sponsors and Collaborators

University of North Carolina, Chapel Hill

National Human Genome Research Institute (NHGRI)

East Carolina University

Mission Health System, Asheville, NC

Investigators

• Study Director: Jeannette T Bensen, Ph.D; University of North Carolina, Chapel Hill
• Principal Investigator: Jonathan S Berg, MD, PhD; University of North Carolina, Chapel Hill

  Study Documents (Full-Text)

Documents provided by University of North Carolina, Chapel Hill:

Informed Consent Form: 7-14 Assent Form 1 Randomization to Research  [PDF] February 28, 2018

Informed Consent Form: 7-14 Assent Form 2 Assent to Research  [PDF] February 28, 2018

Informed Consent Form: 15-17 Assent Form 1 Randomization to Research  [PDF] February 28, 2018

Informed Consent Form: 15-17 Assent Form 2 Assent to Research  [PDF] February 28, 2018

Informed Consent Form: Consent Form 1 Randomization to Research  [PDF] February 28, 2018

Informed Consent Form: Consent Form 2 Assent to Research  [PDF] February 28, 2018

More Information

Additional Information:

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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Staley BS, Milko LV, Waltz M, Griesemer I, Mollison L, Grant TL, Farnan L, Roche M, Navas A, Lightfoot A, Foreman AKM, O'Daniel JM, O'Neill SC, Lin FC, Roman TS, Brandt A, Powell BC, Rini C, Berg JS, Bensen JT. Evaluating the clinical utility of early exome sequencing in diverse pediatric outpatient populations in the North Carolina Clinical Genomic Evaluation of Next-generation Exome Sequencing (NCGENES) 2 study: a randomized controlled trial. Trials. 2021 Jun 14;22(1):395. doi: 10.1186/s13063-021-05341-2.

• Responsible Party: University of North Carolina, Chapel Hill
• ClinicalTrials.gov Identifier: NCT03548779
• Other Study ID Numbers: 17-0816; U01HG006487 ( U.S. NIH Grant/Contract )
• First Posted: June 7, 2018
• Last Update Posted: December 16, 2021
• Last Verified: December 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Plan Description

This study will comply with NIH mandates to share genetic data via submission of raw genotype calls from whole exome sequencing to the database of Genotypes and Phenotypes (dbGaP). All data that is submitted to dbGaP, including individual participant data, is anonymous and includes demographic variables: age of onset, birthplace, sex, race, education level, age. Data is uploaded in batches to the dbGaP website.

Individual-level de-identified coded data will be available to investigators outside of the study team at the end of the study after publication of primary results. Investigators will apply for data by formal submission of a letter of intent that will be reviewed and approved by the study leadership. Investigators of approved projects will sign an inter-institution data sharing agreement (for investigators outside of the studies parent institution). The analytic data set will be shared with the investigator via a secure server restricted by password access.

• Supporting Materials: Study Protocol; Informed Consent Form (ICF)
• Time Frame: Data will be shared following study completion and publication of primary study results.
• Access Criteria: Described above. Access will be by study leadership permission and under an inter-institutional data sharing agreement where relevant
• URL: http://www.med.unc.edu/ncgenes

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

Additional relevant MeSH terms:

Microcephaly; Osteochondrodysplasias; Hearing Loss; Seizures; Movement Disorders; Intellectual Disability; Neuromuscular Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Chromosome Disorders; Disease; Chromosome Aberrations; Autism Spectrum Disorder; Pathologic Processes; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders; Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Neurobehavioral Manifestations; Metabolic Diseases; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Musculoskeletal Diseases