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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Neuromuscular Diseases; Movement Disorders; Intellectual Disability; Autism Spectrum Disorder; Microcephaly; Hearing Loss; Genetic Disease; Inborn Errors of Metabolism; Epilepsy; Seizure; Brain Malformation; Hypotonia; Development Delay; Chromosome Abnormality; Dysmorphic Features; Skeletal Dysplasia; Congenital Abnormality; Macrocephaly
• Intervention / Treatment: Behavioral: Pre-visit prep; Diagnostic test: usual care + exome seq

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 Type: Interventional
• Enrollment (Actual): 806
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Health
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill
    • Greenville, North Carolina, United States, 27858
      • East Carolina University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of in-patient hospital admissions 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.	1 year prior to return of results
Number of in-patient hospital admissions 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.	1 year after return of results
Number of in-patient hospital days 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.	1 year prior to return of results
Number of in-patient hospital days 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.	1 year after return of results
Number of long-term care admissions 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.	1 year prior to return of results
Number of long-term care admissions 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.	1 year after return of results
Number of long-term care days 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.	1 year prior to return of results
Number of long-term care days 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.	1 year after return of results
Number of ER visits 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.	1 year prior to return of results
Number of ER visits 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.	1 year after return of results
Number of specialists visits 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.	1 year prior to return of results
Number of specialists visits 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.	1 year after return of results
Initial Patient Pediatric Quality of Life (Peds QL) score	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.	4-6 weeks prior to clinic visit 1
Final Patient Pediatric Quality of Life (Peds QL) score	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.	6 months after return of results
Initial Caregiver QoL score	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.	4-6 weeks prior to clinic visit 1
Intermediate Caregiver QoL score	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.	2 weeks after return of results
Final Caregiver QoL score	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.	6 months after return of results
Post-Clinic Visit 1 Mean Patient Centeredness Score	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.	Immediately after clinic 1 day of visit 1
Post-Return of Results Mean Patient Centeredness Score	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.	2 weeks after return of results
Number of questions caregiver asks in Clinic Visit 1	Count of number of questions caregiver asks provider in the audio recording of clinic visit 1. Coded by trained study staff.	During clinic 1 day of visit 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Initial Average Peds QL score for "missing school for not feeling well"	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.	4-6 weeks prior to clinic visit 1
Final Average Peds QL score for "missing school for not feeling well"	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.	6 months after return of results
Initial Average Peds QL score for "missing school for doctors visit"	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.	4-6 weeks prior to clinic visit 1
Final Average Peds QL score for "missing school for doctors visit"	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.	6 months after return of results
Initial Amount of work missed because of child's condition or treatments score	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.	4-6 weeks prior to clinic visit 1
Final Amount of work missed because of child's condition or treatments score	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.	6 months after return of results
Initial Difficulty with finishing normal work (including both work outside of the home and housework) because of child's condition or treatments score	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.	4-6 weeks prior to clinic visit 1
Intermediate Difficulty with finishing normal work (including both work outside of the home and housework) because of child's condition or treatments score	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.	2 weeks after return of results
Final Difficulty with finishing normal work (including both work outside of the home and housework) because of child's condition or treatments score	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.	6 months after return of results
Vital status at final f/u	Based on NC Vital Statistics, the child's vital status will be reported as living or deceased.	final follow-up, up to approximately three years after clinic visit 1
Child causes of death related to the primary condition	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.	final follow-up up to approximately three years after clinic visit 1
Percent concordance of caregiver and provider reports of genetic or genomic test 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.	2 weeks after return of results
Mean Baseline Self Efficacy Score	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.	4-6 weeks prior to clinic visit 1
Mean Pre-Clinic Visit 1 Self Efficacy Score	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.	Immediately before Clinic Visit 1
Post-Return of Results Mean FACToR Uncertainty Subscale Score	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.	2 weeks after return of results

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: 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

Publications and helpful links

General Publications

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• ACMG Board of Directors. Clinical utility of genetic and genomic services: a position statement of the American College of Medical Genetics and Genomics. Genet Med. 2015 Jun;17(6):505-7. doi: 10.1038/gim.2015.41. Epub 2015 Mar 12.
• Amendola LM, Dorschner MO, Robertson PD, Salama JS, Hart R, Shirts BH, Murray ML, Tokita MJ, Gallego CJ, Kim DS, Bennett JT, Crosslin DR, Ranchalis J, Jones KL, Rosenthal EA, Jarvik ER, Itsara A, Turner EH, Herman DS, Schleit J, Burt A, Jamal SM, Abrudan JL, Johnson AD, Conlin LK, Dulik MC, Santani A, Metterville DR, Kelly M, Foreman AK, Lee K, Taylor KD, Guo X, Crooks K, Kiedrowski LA, Raffel LJ, Gordon O, Machini K, Desnick RJ, Biesecker LG, Lubitz SA, Mulchandani S, Cooper GM, Joffe S, Richards CS, Yang Y, Rotter JI, Rich SS, O'Donnell CJ, Berg JS, Spinner NB, Evans JP, Fullerton SM, Leppig KA, Bennett RL, Bird T, Sybert VP, Grady WM, Tabor HK, Kim JH, Bamshad MJ, Wilfond B, Motulsky AG, Scott CR, Pritchard CC, Walsh TD, Burke W, Raskind WH, Byers P, Hisama FM, Rehm H, Nickerson DA, Jarvik GP. Actionable exomic incidental findings in 6503 participants: challenges of variant classification. Genome Res. 2015 Mar;25(3):305-15. doi: 10.1101/gr.183483.114. Epub 2015 Jan 30.
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• Berg JS, Foreman AK, O'Daniel JM, Booker JK, Boshe L, Carey T, Crooks KR, Jensen BC, Juengst ET, Lee K, Nelson DK, Powell BC, Powell CM, Roche MI, Skrzynia C, Strande NT, Weck KE, Wilhelmsen KC, Evans JP. A semiquantitative metric for evaluating clinical actionability of incidental or secondary findings from genome-scale sequencing. Genet Med. 2016 May;18(5):467-75. doi: 10.1038/gim.2015.104. Epub 2015 Aug 13.
• Black KZ, Hardy CY, De Marco M, Ammerman AS, Corbie-Smith G, Council B, Ellis D, Eng E, Harris B, Jackson M, Jean-Baptiste J, Kearney W, Legerton M, Parker D, Wynn M, Lightfoot A. Beyond incentives for involvement to compensation for consultants: increasing equity in CBPR approaches. Prog Community Health Partnersh. 2013 Fall;7(3):263-70. doi: 10.1353/cpr.2013.0040.
• Brandes K, Linn AJ, Butow PN, van Weert JC. The characteristics and effectiveness of Question Prompt List interventions in oncology: a systematic review of the literature. Psychooncology. 2015 Mar;24(3):245-52. doi: 10.1002/pon.3637. Epub 2014 Jul 31.
• Burkett K, Morris E, Manning-Courtney P, Anthony J, Shambley-Ebron D. African American families on autism diagnosis and treatment: the influence of culture. J Autism Dev Disord. 2015 Oct;45(10):3244-54. doi: 10.1007/s10803-015-2482-x.
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• Fan Z, Greenwood R, Felix AC, Shiloh-Malawsky Y, Tennison M, Roche M, Crooks K, Weck K, Wilhelmsen K, Berg J, Evans J. GCH1 heterozygous mutation identified by whole-exome sequencing as a treatable condition in a patient presenting with progressive spastic paraplegia. J Neurol. 2014 Mar;261(3):622-4. doi: 10.1007/s00415-014-7265-3. Epub 2014 Feb 8. No abstract available.
• Foreman AK, Lee K, Evans JP. The NCGENES project: exploring the new world of genome sequencing. N C Med J. 2013 Nov-Dec;74(6):500-4.
• Frey LJ, Lenert L, Lopez-Campos G. EHR Big Data Deep Phenotyping. Contribution of the IMIA Genomic Medicine Working Group. Yearb Med Inform. 2014 Aug 15;9(1):206-11. doi: 10.15265/IY-2014-0006.
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Helpful Links

• Agency for Healthcare Research and Quality. Ambulatory care sensitive conditions: age-standardized acute care hospitalization rate for conditions where appropriate ambulatory care prevents or reduces the need for admission to the hospital
• Ales M, Luca L, Marija V, Gorazd R, Karin W, Ana B, Alenka H, Peterlin B. Phenotype-driven gene target definition in clinical genome-wide sequencing data interpretation. Genet Med [Internet]. 2016 Mar 31 [cited 2016 Aug 3]

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2018
• Primary Completion (Actual): September 8, 2023
• Study Completion (Estimated): September 8, 2024

Study Registration Dates

• First Submitted: May 24, 2018
• First Submitted That Met QC Criteria: June 6, 2018
• First Posted (Actual): June 7, 2018

Study Record Updates

• Last Update Posted (Estimated): March 4, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Musculoskeletal Diseases; Otorhinolaryngologic Diseases; Ear Diseases; Bone Diseases; Sensation Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Hearing Disorders; Bone Diseases, Developmental; Congenital Abnormalities; Seizures; Autism Spectrum Disorder; Microcephaly; Hearing Loss; Movement Disorders; Metabolism, Inborn Errors; Intellectual Disability; Chromosome Disorders; Chromosome Aberrations; Genetic Diseases, Inborn; Neuromuscular Diseases; Osteochondrodysplasias
• Other Study ID Numbers: 17-0816; U01HG006487 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD 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.

• IPD Sharing Time Frame: Data will be shared following study completion and publication of primary study results.
• IPD Sharing Access Criteria: Described above. Access will be by study leadership permission and under an inter-institutional data sharing agreement where relevant
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

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