Autism Spectrum Disorder, Brain Malformation, Chromosome Abnormality, Congenital Abnormality, Development Delay, Dysmorphic Features, Epilepsy; Seizure, Genetic Disease, Hearing Loss, Hypotonia, Inborn Errors of Metabolism, Intellectual Disability, Macrocephaly, Microcephaly, Movement Disorders, Neuromuscular Diseases, Skeletal Dysplasia
Conditions
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.
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.
Interventions
BEHAVIORALPre-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_TESTusual 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.
Sponsors
National Human Genome Research Institute (NHGRI)
East Carolina University
Mission Health System, Asheville, NC
University of North Carolina, Chapel Hill
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
DOUBLE (Caregiver, 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.
Eligibility
Sex/Gender
ALL
Age
0 Years to No maximum
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Specialists Visits Among Child Participants 1 Year After Return of Results | 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. Visits were summed across all participants. |
| Final Caregiver QoL Score | 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. |
| Post-Clinic Visit 1 Mean Patient Centeredness Score | 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. Response values will be summed and divided by the total number of items (21) to obtain mean scores ranging from 0-7 where higher values indicate stronger perceptions of patient centeredness. |
| Post-Return of Results Mean Patient Centeredness Score | 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). 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. Response values will be summed and divided by the total number of items (21) to obtain mean scores ranging from 0-7 where higher values indicate stronger perceptions of patient centeredness. |
| Number of Questions Caregiver Asks in Clinic Visit 1 | 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. |
| Number of In-patient Hospital Admissions Among Child Participants 1 Year Prior to Return of Results | 1 year prior to return of results | Count of number of in-patient hospital admissions among child participants during 1 year prior to return of results using data obtained from the Electronic Medical Record. Coded by trained study staff. Admissions were summed across all participants. |
| Number of In-patient Hospital Admissions Among Child Participants 1 Year After Return of Results | 1 year after return of results | Count of number of in-patient hospital admissions among child participants during 1 year after return of results using data obtained from the Electronic Medical Record. Coded by trained study staff. Admissions were summed across all participants. |
| Number of In-patient Hospital Days Among Child Participants 1 Year Prior to Return of Results | 1 year prior to return of results | Count of number of in-patient hospital days among child participants during 1 year prior to return of results using data obtained from the Electronic Medical Record. Coded by trained study staff. Days were summed across all participants. |
| Number of In-patient Hospital Days Among Child Participants 1 Year After Return of Results | 1 year after return of results | Count of number of in-patient hospital days among child participants during 1 year after return of results using data obtained from the Electronic Medical Record. Coded by trained study staff. Days were summed across all participants. |
| Number of Long-term Care Admissions Among Child Participants 1 Year Prior to Return of Results | 1 year prior to return of results | Count of number of long-term care admissions among child participants during 1 year prior to return of results using data obtained from the Electronic Medical Record. Coded by trained study staff. Admissions were summed across all participants. |
| Number of Long-term Care Admissions Among Child Participants 1 Year After Return of Results | 1 year after return of results | Count of number of long-term care admissions among child participants during 1 year after return of results using data obtained from the Electronic Medical Record. Coded by trained study staff. Admissions were summed across all participants. |
| Number of Long-term Care Days Among Child Participants 1 Year Prior to Return of Results | 1 year prior to return of results | Count of number of long-term care days among child participants during 1 year prior to return of results using data obtained from the Electronic Medical Record. Coded by trained study staff. Days were summed across all participants. |
| Number of Long-term Care Days Among Child Participants 1 Year After Return of Results | 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. Days were summed across all participants. |
| Number of ER Visits Among Child Participants 1 Year Prior to Return of Results | 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. Visits were summed across all participants. |
| Number of ER Visits Among Child Participants 1 Year After Return of Results | 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. Visits were summed across all participants. |
| Number of Specialists Visits Among Child Participants 1 Year Prior to Return of Results | 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. Visits were summed across all participants. |
| Initial Patient Pediatric Quality of Life (Peds QL) Score | 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. |
| Final Patient Pediatric Quality of Life (Peds QL) Score | 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. |
| Initial Caregiver QoL Score | 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. |
| Intermediate Caregiver QoL Score | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Final Average Peds QL Score for Missing School for Not Feeling Well | 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. |
| Initial Average Peds QL Score for Missing School for Doctors Visit | 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. |
| Final Average Peds QL Score for Missing School for Doctors Visit | 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. |
| Initial Amount of Work Missed Because of Child's Condition or Treatments Score | 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. |
| Final Amount of Work Missed Because of Child's Condition or Treatments Score | 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. |
| Initial Difficulty With Finishing Normal Work (Including Both Work Outside of the Home and Housework) Because of Child's Condition or Treatments Score | 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. |
| Intermediate Difficulty With Finishing Normal Work (Including Both Work Outside of the Home and Housework) Because of Child's Condition or Treatments Score | 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. |
| Final Difficulty With Finishing Normal Work (Including Both Work Outside of the Home and Housework) Because of Child's Condition or Treatments Score | 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. |
| Percent Concordance of Caregiver and Provider Reports of Genetic or Genomic Test Results | 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. Results are given as the number of parent/caregiver participant responses for each group that were concordant with the provider's diagnostic interpretation of the exome results. |
| Mean Baseline Self Efficacy Score | 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. |
| Mean Pre-Clinic Visit 1 Self Efficacy Score | 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. |
| Post-Return of Results Mean FACToR Uncertainty Subscale Score | 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. |
| Vital Status at Final f/u | 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. |
| Number of Child Participants With Causes of Death Unrelated to the Study | 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. |
| Initial Average Peds QL Score for Missing School for Not Feeling Well | 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. |
Countries
United States
Participant flow
Recruitment details
927 children were eligible for recruitment, and of these 791 parents/caregivers were approached by phone prior to their clinic visit; 514 parents/caregivers were reached for a recruitment phone call, and a total of 417 dyads consisting of a child and their parent/caregiver were enrolled and consented to randomization. Of these, 274 baseline intake forms were obtained at a clinic visit and those dyads continued in the study, for a total of 548 individuals enrolled in the protocol.
Participants by arm
| Arm | Count |
|---|---|
| Parent/Caregiver Pre-visit Prep + Exome Dyads (parent/caregiver + child) randomized to the pre-visit prep arm receive a study packet with educational materials and a question prompt list. The parent/caregiver is 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 the child's clinic visit 1 appointment.
During the clinic visit 1 evaluation, the physician orders any tests deemed clinically appropriate. After completing the clinic visit, dyads randomized to the exome arm are offered exome sequencing in addition to tests ordered by the physician at that visit. The parent/caregiver may decline for their child to have exome sequencing at this point. | 64 |
| Parent/Caregiver Pre-visit Prep + Usual Care Dyads (parent/caregiver + child) randomized to the pre-visit prep arm receive a study packet with educational materials and a question prompt list. The parent/caregiver is 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 the child's clinic visit 1 appointment.
During the clinic visit 1 evaluation, the physician orders any tests deemed clinically appropriate. After completing the clinic visit, dyads randomized to the usual care arm are not offered additional exome sequencing. | 72 |
| Parent/Caregiver No Pre-visit Prep + Exome Dyads (parent/caregiver + child) randomized to the no pre-visit prep arm receive a mailed card reminding them about their upcoming clinic visit.
During the clinic visit 1 evaluation, the physician orders any tests deemed clinically appropriate. After completing the clinic visit, dyads randomized to the exome arm are offered exome sequencing in addition to tests ordered by the physician at that visit. The parent/caregiver may decline for their child to have exome sequencing at this point. | 63 |
| Parent/Caregiver No Pre-visit Prep + Usual Care Dyads (parent/caregiver + child) randomized to the no pre-visit prep arm receive a mailed card reminding them about their upcoming clinic visit.
During the clinic visit 1 evaluation, the physician orders any tests deemed clinically appropriate. After completing the clinic visit, dyads randomized to the usual care arm are not offered additional exome sequencing. | 75 |
| Child Pre-visit Prep + Exome Dyads (parent/caregiver + child) randomized to the pre-visit prep arm receive a study packet with educational materials and a question prompt list. The parent/caregiver is 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 the child's clinic visit 1 appointment.
During the clinic visit 1 evaluation, the physician orders any tests deemed clinically appropriate. After completing the clinic visit, dyads randomized to the exome arm are offered exome sequencing in addition to tests ordered by the physician at that visit. The parent/caregiver may decline for their child to have exome sequencing at this point. | 64 |
| Child Pre-visit Prep + Usual Care Dyads (parent/caregiver + child) randomized to the pre-visit prep arm receive a study packet with educational materials and a question prompt list. The parent/caregiver is 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 the child's clinic visit 1 appointment.
During the clinic visit 1 evaluation, the physician orders any tests deemed clinically appropriate. After completing the clinic visit, dyads randomized to the usual care arm are not offered additional exome sequencing. | 72 |
| Child No Pre-visit Prep + Exome Dyads (parent/caregiver + child) randomized to the no pre-visit prep arm receive a mailed card reminding them about their upcoming clinic visit.
During the clinic visit 1 evaluation, the physician orders any tests deemed clinically appropriate. After completing the clinic visit, dyads randomized to the exome arm are offered exome sequencing in addition to tests ordered by the physician at that visit. The parent/caregiver may decline for their child to have exome sequencing at this point. | 63 |
| Child No Pre-visit Prep + Usual Care Dyads (parent/caregiver + child) randomized to the no pre-visit prep arm receive a mailed card reminding them about their upcoming clinic visit.
During the clinic visit 1 evaluation, the physician orders any tests deemed clinically appropriate. After completing the clinic visit, dyads randomized to the usual care arm are not offered additional exome sequencing. | 75 |
| Total | 548 |
Baseline characteristics
| Characteristic | Parent/Caregiver Pre-visit Prep + Exome | Parent/Caregiver Pre-visit Prep + Usual Care | Parent/Caregiver No Pre-visit Prep + Exome | Parent/Caregiver No Pre-visit Prep + Usual Care | Child Pre-visit Prep + Exome | Total | Child Pre-visit Prep + Usual Care | Child No Pre-visit Prep + Exome | Child No Pre-visit Prep + Usual Care |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 35.3 years STANDARD_DEVIATION 6.7 | 35.8 years STANDARD_DEVIATION 7 | 36.6 years STANDARD_DEVIATION 9.5 | 35.3 years STANDARD_DEVIATION 9.3 | 5.4 years STANDARD_DEVIATION 4.3 | 20.8 years STANDARD_DEVIATION 16.4 | 5.1 years STANDARD_DEVIATION 4.3 | 6.8 years STANDARD_DEVIATION 4.6 | 6.2 years STANDARD_DEVIATION 4.1 |
| Race/Ethnicity, Customized American Indian, Native American, or Alaska Native | 2 Participants | 4 Participants | 3 Participants | 4 Participants | 1 Participants | 23 Participants | 4 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 3 Participants | 13 Participants | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 7 Participants | 11 Participants | 10 Participants | 5 Participants | 8 Participants | 72 Participants | 14 Participants | 10 Participants | 7 Participants |
| Race/Ethnicity, Customized Hispanic/Latino(a) | 4 Participants | 5 Participants | 2 Participants | 10 Participants | 7 Participants | 50 Participants | 7 Participants | 2 Participants | 13 Participants |
| Race/Ethnicity, Customized Middle Eastern or North African/Mediterranean | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian/Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Prefer not to answer | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Unknown/none of these fully describe me | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 5 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White or European American | 52 Participants | 49 Participants | 49 Participants | 54 Participants | 49 Participants | 408 Participants | 50 Participants | 48 Participants | 57 Participants |
| Sex/Gender, Customized Did not answer | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 0 Participants | 7 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex/Gender, Customized Female | 59 Participants | 67 Participants | 58 Participants | 67 Participants | 28 Participants | 371 Participants | 31 Participants | 24 Participants | 37 Participants |
| Sex/Gender, Customized Male | 3 Participants | 3 Participants | 4 Participants | 6 Participants | 36 Participants | 170 Participants | 41 Participants | 39 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 53 | 1 / 70 | 0 / 59 | 0 / 68 |
| other Total, other adverse events | 0 / 53 | 0 / 70 | 0 / 59 | 0 / 68 |
| serious Total, serious adverse events | 0 / 53 | 1 / 70 | 0 / 59 | 0 / 68 |
Outcome results
Primary
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.
Time frame: 6 months after return of results
Population: This analysis is conducted among the parent/caregiver participants only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Parent/Caregiver Pre-visit Prep + Exome | Final Caregiver QoL Score | 53.31 score on a scale | Standard Deviation 5.41 |
| Parent/Caregiver Pre-visit Prep + Usual Care | Final Caregiver QoL Score | 50.38 score on a scale | Standard Deviation 8.21 |
| Parent/Caregiver No Pre-visit Prep + Exome | Final Caregiver QoL Score | 47.41 score on a scale | Standard Deviation 11.44 |
| Parent/Caregiver No Pre-visit Prep + Usual Care | Final Caregiver QoL Score | 47.46 score on a scale | Standard Deviation 10.39 |
Primary
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.
Time frame: 6 months after return of results
Population: This analysis is conducted among the parent/caregiver participants only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Parent/Caregiver Pre-visit Prep + Exome | Final Patient Pediatric Quality of Life (Peds QL) Score | 72.15 score on a scale | Standard Deviation 17.95 |
| Parent/Caregiver Pre-visit Prep + Usual Care | Final Patient Pediatric Quality of Life (Peds QL) Score | 75.74 score on a scale | Standard Deviation 15.01 |
| Parent/Caregiver No Pre-visit Prep + Exome | Final Patient Pediatric Quality of Life (Peds QL) Score | 71.65 score on a scale | Standard Deviation 17.1 |
| Parent/Caregiver No Pre-visit Prep + Usual Care | Final Patient Pediatric Quality of Life (Peds QL) Score | 68.90 score on a scale | Standard Deviation 19.01 |
Primary
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.
Time frame: 4-6 weeks prior to clinic visit 1
Population: This analysis is conducted among the parent/caregiver participants only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Parent/Caregiver Pre-visit Prep + Exome | Initial Caregiver QoL Score | 50.14 score on a scale | Standard Deviation 10.25 |
| Parent/Caregiver Pre-visit Prep + Usual Care | Initial Caregiver QoL Score | 48.84 score on a scale | Standard Deviation 8.14 |
| Parent/Caregiver No Pre-visit Prep + Exome | Initial Caregiver QoL Score | 51.30 score on a scale | Standard Deviation 8.72 |
| Parent/Caregiver No Pre-visit Prep + Usual Care | Initial Caregiver QoL Score | 47.69 score on a scale | Standard Deviation 9.59 |
Primary
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.
Time frame: 4-6 weeks prior to clinic visit 1
Population: This analysis is conducted among the parent/caregiver participants only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Parent/Caregiver Pre-visit Prep + Exome | Initial Patient Pediatric Quality of Life (Peds QL) Score | 64.37 score on a scale | Standard Deviation 20.59 |
| Parent/Caregiver Pre-visit Prep + Usual Care | Initial Patient Pediatric Quality of Life (Peds QL) Score | 65.83 score on a scale | Standard Deviation 18 |
| Parent/Caregiver No Pre-visit Prep + Exome | Initial Patient Pediatric Quality of Life (Peds QL) Score | 60.04 score on a scale | Standard Deviation 17.1 |
| Parent/Caregiver No Pre-visit Prep + Usual Care | Initial Patient Pediatric Quality of Life (Peds QL) Score | 63.39 score on a scale | Standard Deviation 18.49 |
Primary
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.
Time frame: 2 weeks after return of results
Population: This analysis is conducted among the parent/caregiver participants only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Parent/Caregiver Pre-visit Prep + Exome | Intermediate Caregiver QoL Score | 51.48 score on a scale | Standard Deviation 9.03 |
| Parent/Caregiver Pre-visit Prep + Usual Care | Intermediate Caregiver QoL Score | 46.58 score on a scale | Standard Deviation 9.68 |
| Parent/Caregiver No Pre-visit Prep + Exome | Intermediate Caregiver QoL Score | 50.66 score on a scale | Standard Deviation 11.49 |
| Parent/Caregiver No Pre-visit Prep + Usual Care | Intermediate Caregiver QoL Score | 50.08 score on a scale | Standard Deviation 7.52 |
Primary
Number of ER Visits Among Child Participants 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. Visits were summed across all participants.
Time frame: 1 year after return of results
Population: This analysis includes the subset of child participants with 12 months of EHR data available before and after study results were returned.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Parent/Caregiver Pre-visit Prep + Exome | Number of ER Visits Among Child Participants 1 Year After Return of Results | 10 ER visits |
| Parent/Caregiver Pre-visit Prep + Usual Care | Number of ER Visits Among Child Participants 1 Year After Return of Results | 29 ER visits |
| Parent/Caregiver No Pre-visit Prep + Exome | Number of ER Visits Among Child Participants 1 Year After Return of Results | 20 ER visits |
| Parent/Caregiver No Pre-visit Prep + Usual Care | Number of ER Visits Among Child Participants 1 Year After Return of Results | 23 ER visits |
Primary
Number of ER Visits Among Child Participants 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. Visits were summed across all participants.
Time frame: 1 year prior to return of results
Population: This analysis includes the subset of child participants with 12 months of EHR data available before and after study results were returned.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Parent/Caregiver Pre-visit Prep + Exome | Number of ER Visits Among Child Participants 1 Year Prior to Return of Results | 15 ER visits |
| Parent/Caregiver Pre-visit Prep + Usual Care | Number of ER Visits Among Child Participants 1 Year Prior to Return of Results | 25 ER visits |
| Parent/Caregiver No Pre-visit Prep + Exome | Number of ER Visits Among Child Participants 1 Year Prior to Return of Results | 35 ER visits |
| Parent/Caregiver No Pre-visit Prep + Usual Care | Number of ER Visits Among Child Participants 1 Year Prior to Return of Results | 35 ER visits |
Primary
Number of In-patient Hospital Admissions Among Child Participants 1 Year After Return of Results
Count of number of in-patient hospital admissions among child participants during 1 year after return of results using data obtained from the Electronic Medical Record. Coded by trained study staff. Admissions were summed across all participants.
Time frame: 1 year after return of results
Population: This analysis includes the subset of child participants with 12 months of EHR data available before and after study results were returned.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Parent/Caregiver Pre-visit Prep + Exome | Number of In-patient Hospital Admissions Among Child Participants 1 Year After Return of Results | 1 In-patient hospital admissions |
| Parent/Caregiver Pre-visit Prep + Usual Care | Number of In-patient Hospital Admissions Among Child Participants 1 Year After Return of Results | 1 In-patient hospital admissions |
| Parent/Caregiver No Pre-visit Prep + Exome | Number of In-patient Hospital Admissions Among Child Participants 1 Year After Return of Results | 8 In-patient hospital admissions |
| Parent/Caregiver No Pre-visit Prep + Usual Care | Number of In-patient Hospital Admissions Among Child Participants 1 Year After Return of Results | 2 In-patient hospital admissions |
Primary
Number of In-patient Hospital Admissions Among Child Participants 1 Year Prior to Return of Results
Count of number of in-patient hospital admissions among child participants during 1 year prior to return of results using data obtained from the Electronic Medical Record. Coded by trained study staff. Admissions were summed across all participants.
Time frame: 1 year prior to return of results
Population: This analysis includes the subset of child participants with 12 months of EHR data available before and after study results were returned.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Parent/Caregiver Pre-visit Prep + Exome | Number of In-patient Hospital Admissions Among Child Participants 1 Year Prior to Return of Results | 0 In-patient hospital admissions |
| Parent/Caregiver Pre-visit Prep + Usual Care | Number of In-patient Hospital Admissions Among Child Participants 1 Year Prior to Return of Results | 3 In-patient hospital admissions |
| Parent/Caregiver No Pre-visit Prep + Exome | Number of In-patient Hospital Admissions Among Child Participants 1 Year Prior to Return of Results | 4 In-patient hospital admissions |
| Parent/Caregiver No Pre-visit Prep + Usual Care | Number of In-patient Hospital Admissions Among Child Participants 1 Year Prior to Return of Results | 2 In-patient hospital admissions |
Primary
Number of In-patient Hospital Days Among Child Participants 1 Year After Return of Results
Count of number of in-patient hospital days among child participants during 1 year after return of results using data obtained from the Electronic Medical Record. Coded by trained study staff. Days were summed across all participants.
Time frame: 1 year after return of results
Population: This analysis includes the subset of child participants with 12 months of EHR data available before and after study results were returned.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Parent/Caregiver Pre-visit Prep + Exome | Number of In-patient Hospital Days Among Child Participants 1 Year After Return of Results | 5 In-patient hospital days |
| Parent/Caregiver Pre-visit Prep + Usual Care | Number of In-patient Hospital Days Among Child Participants 1 Year After Return of Results | 5 In-patient hospital days |
| Parent/Caregiver No Pre-visit Prep + Exome | Number of In-patient Hospital Days Among Child Participants 1 Year After Return of Results | 148 In-patient hospital days |
| Parent/Caregiver No Pre-visit Prep + Usual Care | Number of In-patient Hospital Days Among Child Participants 1 Year After Return of Results | 11 In-patient hospital days |
Primary
Number of In-patient Hospital Days Among Child Participants 1 Year Prior to Return of Results
Count of number of in-patient hospital days among child participants during 1 year prior to return of results using data obtained from the Electronic Medical Record. Coded by trained study staff. Days were summed across all participants.
Time frame: 1 year prior to return of results
Population: This analysis includes the subset of child participants with 12 months of EHR data available before and after study results were returned.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Parent/Caregiver Pre-visit Prep + Exome | Number of In-patient Hospital Days Among Child Participants 1 Year Prior to Return of Results | 0 In-patient hospital days |
| Parent/Caregiver Pre-visit Prep + Usual Care | Number of In-patient Hospital Days Among Child Participants 1 Year Prior to Return of Results | 13 In-patient hospital days |
| Parent/Caregiver No Pre-visit Prep + Exome | Number of In-patient Hospital Days Among Child Participants 1 Year Prior to Return of Results | 22 In-patient hospital days |
| Parent/Caregiver No Pre-visit Prep + Usual Care | Number of In-patient Hospital Days Among Child Participants 1 Year Prior to Return of Results | 1 In-patient hospital days |
Primary
Number of Long-term Care Admissions Among Child Participants 1 Year After Return of Results
Count of number of long-term care admissions among child participants during 1 year after return of results using data obtained from the Electronic Medical Record. Coded by trained study staff. Admissions were summed across all participants.
Time frame: 1 year after return of results
Population: This analysis includes the subset of child participants with 12 months of EHR data available before and after study results were returned.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Parent/Caregiver Pre-visit Prep + Exome | Number of Long-term Care Admissions Among Child Participants 1 Year After Return of Results | 0 Long-term care admissions |
| Parent/Caregiver Pre-visit Prep + Usual Care | Number of Long-term Care Admissions Among Child Participants 1 Year After Return of Results | 0 Long-term care admissions |
| Parent/Caregiver No Pre-visit Prep + Exome | Number of Long-term Care Admissions Among Child Participants 1 Year After Return of Results | 3 Long-term care admissions |
| Parent/Caregiver No Pre-visit Prep + Usual Care | Number of Long-term Care Admissions Among Child Participants 1 Year After Return of Results | 0 Long-term care admissions |
Primary
Number of Long-term Care Admissions Among Child Participants 1 Year Prior to Return of Results
Count of number of long-term care admissions among child participants during 1 year prior to return of results using data obtained from the Electronic Medical Record. Coded by trained study staff. Admissions were summed across all participants.
Time frame: 1 year prior to return of results
Population: This analysis includes the subset of child participants with 12 months of EHR data available before and after study results were returned.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Parent/Caregiver Pre-visit Prep + Exome | Number of Long-term Care Admissions Among Child Participants 1 Year Prior to Return of Results | 0 Long-term care admissions |
| Parent/Caregiver Pre-visit Prep + Usual Care | Number of Long-term Care Admissions Among Child Participants 1 Year Prior to Return of Results | 0 Long-term care admissions |
| Parent/Caregiver No Pre-visit Prep + Exome | Number of Long-term Care Admissions Among Child Participants 1 Year Prior to Return of Results | 4 Long-term care admissions |
| Parent/Caregiver No Pre-visit Prep + Usual Care | Number of Long-term Care Admissions Among Child Participants 1 Year Prior to Return of Results | 0 Long-term care admissions |
Primary
Number of Long-term Care Days Among Child Participants 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. Days were summed across all participants.
Time frame: 1 year after return of results
Population: This analysis includes the subset of child participants with 12 months of EHR data available before and after study results were returned.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Parent/Caregiver Pre-visit Prep + Exome | Number of Long-term Care Days Among Child Participants 1 Year After Return of Results | 0 Long-term care days |
| Parent/Caregiver Pre-visit Prep + Usual Care | Number of Long-term Care Days Among Child Participants 1 Year After Return of Results | 0 Long-term care days |
| Parent/Caregiver No Pre-visit Prep + Exome | Number of Long-term Care Days Among Child Participants 1 Year After Return of Results | 17 Long-term care days |
| Parent/Caregiver No Pre-visit Prep + Usual Care | Number of Long-term Care Days Among Child Participants 1 Year After Return of Results | 0 Long-term care days |
Primary
Number of Long-term Care Days Among Child Participants 1 Year Prior to Return of Results
Count of number of long-term care days among child participants during 1 year prior to return of results using data obtained from the Electronic Medical Record. Coded by trained study staff. Days were summed across all participants.
Time frame: 1 year prior to return of results
Population: This analysis includes the subset of child participants with 12 months of EHR data available before and after study results were returned.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Parent/Caregiver Pre-visit Prep + Exome | Number of Long-term Care Days Among Child Participants 1 Year Prior to Return of Results | 0 Long-term care days |
| Parent/Caregiver Pre-visit Prep + Usual Care | Number of Long-term Care Days Among Child Participants 1 Year Prior to Return of Results | 0 Long-term care days |
| Parent/Caregiver No Pre-visit Prep + Exome | Number of Long-term Care Days Among Child Participants 1 Year Prior to Return of Results | 29 Long-term care days |
| Parent/Caregiver No Pre-visit Prep + Usual Care | Number of Long-term Care Days Among Child Participants 1 Year Prior to Return of Results | 0 Long-term care days |
Primary
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.
Time frame: During clinic 1 day of visit 1
Population: This analysis is conducted among the parent/caregiver participants who attended a clinic visit that was transcribed (a subset of all dyads who completed Clinic Visit 1). The analysis populations only represent the first randomization (Pre-visit prep vs. No pre-visit prep) because the second randomization (Exome vs. Usual care) did not occur until after the clinic visit was completed, and was therefore not germane to this specific outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Parent/Caregiver Pre-visit Prep + Exome | Number of Questions Caregiver Asks in Clinic Visit 1 | 4.36 Number of questions asked | Standard Deviation 4.66 |
| Parent/Caregiver Pre-visit Prep + Usual Care | Number of Questions Caregiver Asks in Clinic Visit 1 | 2.83 Number of questions asked | Standard Deviation 3.03 |
Primary
Number of Specialists Visits Among Child Participants 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. Visits were summed across all participants.
Time frame: 1 year after return of results
Population: This analysis includes the subset of child participants with 12 months of EHR data available before and after study results were returned.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Parent/Caregiver Pre-visit Prep + Exome | Number of Specialists Visits Among Child Participants 1 Year After Return of Results | 220 Specialist visits |
| Parent/Caregiver Pre-visit Prep + Usual Care | Number of Specialists Visits Among Child Participants 1 Year After Return of Results | 556 Specialist visits |
| Parent/Caregiver No Pre-visit Prep + Exome | Number of Specialists Visits Among Child Participants 1 Year After Return of Results | 650 Specialist visits |
| Parent/Caregiver No Pre-visit Prep + Usual Care | Number of Specialists Visits Among Child Participants 1 Year After Return of Results | 273 Specialist visits |
Primary
Number of Specialists Visits Among Child Participants 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. Visits were summed across all participants.
Time frame: 1 year prior to return of results
Population: This analysis includes the subset of child participants with 12 months of EHR data available before and after study results were returned.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Parent/Caregiver Pre-visit Prep + Exome | Number of Specialists Visits Among Child Participants 1 Year Prior to Return of Results | 202 Specialist visits |
| Parent/Caregiver Pre-visit Prep + Usual Care | Number of Specialists Visits Among Child Participants 1 Year Prior to Return of Results | 665 Specialist visits |
| Parent/Caregiver No Pre-visit Prep + Exome | Number of Specialists Visits Among Child Participants 1 Year Prior to Return of Results | 663 Specialist visits |
| Parent/Caregiver No Pre-visit Prep + Usual Care | Number of Specialists Visits Among Child Participants 1 Year Prior to Return of Results | 332 Specialist visits |
Primary
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. Response values will be summed and divided by the total number of items (21) to obtain mean scores ranging from 0-7 where higher values indicate stronger perceptions of patient centeredness.
Time frame: Immediately after clinic 1 day of visit 1
Population: This analysis is conducted among the parent/caregiver participants only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Parent/Caregiver Pre-visit Prep + Exome | Post-Clinic Visit 1 Mean Patient Centeredness Score | 5.7 score on a scale | Standard Deviation 0.8 |
| Parent/Caregiver Pre-visit Prep + Usual Care | Post-Clinic Visit 1 Mean Patient Centeredness Score | 5.7 score on a scale | Standard Deviation 0.9 |
| Parent/Caregiver No Pre-visit Prep + Exome | Post-Clinic Visit 1 Mean Patient Centeredness Score | 5.9 score on a scale | Standard Deviation 0.7 |
| Parent/Caregiver No Pre-visit Prep + Usual Care | Post-Clinic Visit 1 Mean Patient Centeredness Score | 5.8 score on a scale | Standard Deviation 0.9 |
Primary
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). 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. Response values will be summed and divided by the total number of items (21) to obtain mean scores ranging from 0-7 where higher values indicate stronger perceptions of patient centeredness.
Time frame: 2 weeks after return of results
Population: This analysis is conducted among the parent/caregiver participants only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Parent/Caregiver Pre-visit Prep + Exome | Post-Return of Results Mean Patient Centeredness Score | 5.5 score on a scale | Standard Deviation 0.9 |
| Parent/Caregiver Pre-visit Prep + Usual Care | Post-Return of Results Mean Patient Centeredness Score | 5 score on a scale | Standard Deviation 1.3 |
| Parent/Caregiver No Pre-visit Prep + Exome | Post-Return of Results Mean Patient Centeredness Score | 5 score on a scale | Standard Deviation 1.1 |
| Parent/Caregiver No Pre-visit Prep + Usual Care | Post-Return of Results Mean Patient Centeredness Score | 4.8 score on a scale | Standard Deviation 1.6 |
Secondary
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.
Time frame: 6 months after return of results
Population: This analysis is conducted among the parent/caregiver participants only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Parent/Caregiver Pre-visit Prep + Exome | Final Amount of Work Missed Because of Child's Condition or Treatments Score | 2.3 score on a scale | Standard Deviation 1.7 |
| Parent/Caregiver Pre-visit Prep + Usual Care | Final Amount of Work Missed Because of Child's Condition or Treatments Score | 2.3 score on a scale | Standard Deviation 1.8 |
| Parent/Caregiver No Pre-visit Prep + Exome | Final Amount of Work Missed Because of Child's Condition or Treatments Score | 2.5 score on a scale | Standard Deviation 1.8 |
| Parent/Caregiver No Pre-visit Prep + Usual Care | Final Amount of Work Missed Because of Child's Condition or Treatments Score | 2.6 score on a scale | Standard Deviation 2 |
Secondary
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.
Time frame: 6 months after return of results
Population: This analysis is conducted among the parent/caregiver participants only. The parent/caregiver completes this measure as a proxy for the child.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Parent/Caregiver Pre-visit Prep + Exome | Final Average Peds QL Score for Missing School for Doctors Visit | 77.1 score on a scale | Standard Deviation 23.8 |
| Parent/Caregiver Pre-visit Prep + Usual Care | Final Average Peds QL Score for Missing School for Doctors Visit | 82.6 score on a scale | Standard Deviation 21.4 |
| Parent/Caregiver No Pre-visit Prep + Exome | Final Average Peds QL Score for Missing School for Doctors Visit | 78.9 score on a scale | Standard Deviation 23.3 |
| Parent/Caregiver No Pre-visit Prep + Usual Care | Final Average Peds QL Score for Missing School for Doctors Visit | 82.5 score on a scale | Standard Deviation 19.5 |
Secondary
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.
Time frame: 6 months after return of results
Population: This analysis is conducted among the parent/caregiver participants only. The parent/caregiver completes this measure as a proxy for the child.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Parent/Caregiver Pre-visit Prep + Exome | Final Average Peds QL Score for Missing School for Not Feeling Well | 77.1 score on a scale | Standard Deviation 23.8 |
| Parent/Caregiver Pre-visit Prep + Usual Care | Final Average Peds QL Score for Missing School for Not Feeling Well | 82.6 score on a scale | Standard Deviation 22.6 |
| Parent/Caregiver No Pre-visit Prep + Exome | Final Average Peds QL Score for Missing School for Not Feeling Well | 78.9 score on a scale | Standard Deviation 23.3 |
| Parent/Caregiver No Pre-visit Prep + Usual Care | Final Average Peds QL Score for Missing School for Not Feeling Well | 81.3 score on a scale | Standard Deviation 22.2 |
Secondary
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.
Time frame: 6 months after return of results
Population: This analysis is conducted among the parent/caregiver participants only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Parent/Caregiver Pre-visit Prep + Exome | Final Difficulty With Finishing Normal Work (Including Both Work Outside of the Home and Housework) Because of Child's Condition or Treatments Score | 2.1 score on a scale | Standard Deviation 1.4 |
| Parent/Caregiver Pre-visit Prep + Usual Care | Final Difficulty With Finishing Normal Work (Including Both Work Outside of the Home and Housework) Because of Child's Condition or Treatments Score | 2.1 score on a scale | Standard Deviation 1.3 |
| Parent/Caregiver No Pre-visit Prep + Exome | Final Difficulty With Finishing Normal Work (Including Both Work Outside of the Home and Housework) Because of Child's Condition or Treatments Score | 2.1 score on a scale | Standard Deviation 1.1 |
| Parent/Caregiver No Pre-visit Prep + Usual Care | Final Difficulty With Finishing Normal Work (Including Both Work Outside of the Home and Housework) Because of Child's Condition or Treatments Score | 2.1 score on a scale | Standard Deviation 1.2 |
Secondary
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.
Time frame: 4-6 weeks prior to clinic visit 1
Population: This analysis is conducted among the parent/caregiver participants only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Parent/Caregiver Pre-visit Prep + Exome | Initial Amount of Work Missed Because of Child's Condition or Treatments Score | 2.3 score on a scale | Standard Deviation 1.7 |
| Parent/Caregiver Pre-visit Prep + Usual Care | Initial Amount of Work Missed Because of Child's Condition or Treatments Score | 2.4 score on a scale | Standard Deviation 1.9 |
| Parent/Caregiver No Pre-visit Prep + Exome | Initial Amount of Work Missed Because of Child's Condition or Treatments Score | 2.5 score on a scale | Standard Deviation 1.8 |
| Parent/Caregiver No Pre-visit Prep + Usual Care | Initial Amount of Work Missed Because of Child's Condition or Treatments Score | 2 score on a scale | Standard Deviation 1.4 |
Secondary
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.
Time frame: 4-6 weeks prior to clinic visit 1
Population: This analysis is conducted among the parent/caregiver participants only. The parent/caregiver completes this measure as a proxy for the child.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Parent/Caregiver Pre-visit Prep + Exome | Initial Average Peds QL Score for Missing School for Doctors Visit | 59.7 score on a scale | Standard Deviation 28.4 |
| Parent/Caregiver Pre-visit Prep + Usual Care | Initial Average Peds QL Score for Missing School for Doctors Visit | 65 score on a scale | Standard Deviation 27.8 |
| Parent/Caregiver No Pre-visit Prep + Exome | Initial Average Peds QL Score for Missing School for Doctors Visit | 54.9 score on a scale | Standard Deviation 27.2 |
| Parent/Caregiver No Pre-visit Prep + Usual Care | Initial Average Peds QL Score for Missing School for Doctors Visit | 60 score on a scale | Standard Deviation 26.9 |
Secondary
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.
Time frame: 4-6 weeks prior to clinic visit 1
Population: This analysis is conducted among the parent/caregiver participants only. The parent/caregiver completes this measure as a proxy for the child.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Parent/Caregiver Pre-visit Prep + Exome | Initial Average Peds QL Score for Missing School for Not Feeling Well | 70.8 score on a scale | Standard Deviation 29.8 |
| Parent/Caregiver Pre-visit Prep + Usual Care | Initial Average Peds QL Score for Missing School for Not Feeling Well | 80.6 score on a scale | Standard Deviation 20.5 |
| Parent/Caregiver No Pre-visit Prep + Exome | Initial Average Peds QL Score for Missing School for Not Feeling Well | 65.5 score on a scale | Standard Deviation 28.3 |
| Parent/Caregiver No Pre-visit Prep + Usual Care | Initial Average Peds QL Score for Missing School for Not Feeling Well | 73 score on a scale | Standard Deviation 28.7 |
Secondary
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.
Time frame: 4-6 weeks prior to clinic visit 1
Population: This analysis is conducted among the parent/caregiver participants only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Parent/Caregiver Pre-visit Prep + Exome | Initial Difficulty With Finishing Normal Work (Including Both Work Outside of the Home and Housework) Because of Child's Condition or Treatments Score | 2.7 score on a scale | Standard Deviation 1.4 |
| Parent/Caregiver Pre-visit Prep + Usual Care | Initial Difficulty With Finishing Normal Work (Including Both Work Outside of the Home and Housework) Because of Child's Condition or Treatments Score | 2.5 score on a scale | Standard Deviation 1.3 |
| Parent/Caregiver No Pre-visit Prep + Exome | Initial Difficulty With Finishing Normal Work (Including Both Work Outside of the Home and Housework) Because of Child's Condition or Treatments Score | 2.7 score on a scale | Standard Deviation 1.2 |
| Parent/Caregiver No Pre-visit Prep + Usual Care | Initial Difficulty With Finishing Normal Work (Including Both Work Outside of the Home and Housework) Because of Child's Condition or Treatments Score | 2.4 score on a scale | Standard Deviation 1.2 |
Secondary
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.
Time frame: 2 weeks after return of results
Population: This analysis is conducted among the parent/caregiver participants only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Parent/Caregiver Pre-visit Prep + Exome | Intermediate Difficulty With Finishing Normal Work (Including Both Work Outside of the Home and Housework) Because of Child's Condition or Treatments Score | 1.9 score on a scale | Standard Deviation 1.1 |
| Parent/Caregiver Pre-visit Prep + Usual Care | Intermediate Difficulty With Finishing Normal Work (Including Both Work Outside of the Home and Housework) Because of Child's Condition or Treatments Score | 2 score on a scale | Standard Deviation 1.1 |
| Parent/Caregiver No Pre-visit Prep + Exome | Intermediate Difficulty With Finishing Normal Work (Including Both Work Outside of the Home and Housework) Because of Child's Condition or Treatments Score | 2.3 score on a scale | Standard Deviation 1.3 |
| Parent/Caregiver No Pre-visit Prep + Usual Care | Intermediate Difficulty With Finishing Normal Work (Including Both Work Outside of the Home and Housework) Because of Child's Condition or Treatments Score | 2.1 score on a scale | Standard Deviation 1.1 |
Secondary
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.
Time frame: 4-6 weeks prior to clinic visit 1
Population: This analysis is conducted among the parent/caregiver participants only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Parent/Caregiver Pre-visit Prep + Exome | Mean Baseline Self Efficacy Score | 4.5 score on a scale | Standard Deviation 0.5 |
| Parent/Caregiver Pre-visit Prep + Usual Care | Mean Baseline Self Efficacy Score | 4.5 score on a scale | Standard Deviation 0.6 |
| Parent/Caregiver No Pre-visit Prep + Exome | Mean Baseline Self Efficacy Score | 4.6 score on a scale | Standard Deviation 0.4 |
| Parent/Caregiver No Pre-visit Prep + Usual Care | Mean Baseline Self Efficacy Score | 4.6 score on a scale | Standard Deviation 0.5 |
Secondary
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.
Time frame: Immediately before Clinic Visit 1
Population: This analysis is conducted among the parent/caregiver participants only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Parent/Caregiver Pre-visit Prep + Exome | Mean Pre-Clinic Visit 1 Self Efficacy Score | 4.6 score on a scale | Standard Deviation 0.5 |
| Parent/Caregiver Pre-visit Prep + Usual Care | Mean Pre-Clinic Visit 1 Self Efficacy Score | 4.4 score on a scale | Standard Deviation 0.8 |
| Parent/Caregiver No Pre-visit Prep + Exome | Mean Pre-Clinic Visit 1 Self Efficacy Score | 4.5 score on a scale | Standard Deviation 0.5 |
| Parent/Caregiver No Pre-visit Prep + Usual Care | Mean Pre-Clinic Visit 1 Self Efficacy Score | 4.4 score on a scale | Standard Deviation 0.6 |
Secondary
Number of Child Participants With Causes of Death Unrelated to the Study
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.
Time frame: Final follow-up, up to approximately three years after clinic visit 1
Population: One child participant died during the course of the study follow-up period, unrelated to the study intervention. Cause of death was multiple organ failure and septic shock.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Parent/Caregiver Pre-visit Prep + Exome | Number of Child Participants With Causes of Death Unrelated to the Study | 0 Participants |
| Parent/Caregiver Pre-visit Prep + Usual Care | Number of Child Participants With Causes of Death Unrelated to the Study | 1 Participants |
| Parent/Caregiver No Pre-visit Prep + Exome | Number of Child Participants With Causes of Death Unrelated to the Study | 0 Participants |
| Parent/Caregiver No Pre-visit Prep + Usual Care | Number of Child Participants With Causes of Death Unrelated to the Study | 0 Participants |
Secondary
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. Results are given as the number of parent/caregiver participant responses for each group that were concordant with the provider's diagnostic interpretation of the exome results.
Time frame: 2 weeks after return of results
Population: This analysis is only performed in the subset of parent/caregiver participants whose child was randomized to receive exome sequencing and received an interpretation of their exome data from a provider.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Parent/Caregiver Pre-visit Prep + Exome | Percent Concordance of Caregiver and Provider Reports of Genetic or Genomic Test Results | 9 participants |
| Parent/Caregiver Pre-visit Prep + Usual Care | Percent Concordance of Caregiver and Provider Reports of Genetic or Genomic Test Results | 12 participants |
Secondary
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.
Time frame: 2 weeks after return of results
Population: This analysis is conducted among the parent/caregiver participants only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Parent/Caregiver Pre-visit Prep + Exome | Post-Return of Results Mean FACToR Uncertainty Subscale Score | 1.7 score on a scale | Standard Deviation 0.6 |
| Parent/Caregiver Pre-visit Prep + Usual Care | Post-Return of Results Mean FACToR Uncertainty Subscale Score | 2.4 score on a scale | Standard Deviation 1.1 |
| Parent/Caregiver No Pre-visit Prep + Exome | Post-Return of Results Mean FACToR Uncertainty Subscale Score | 2.3 score on a scale | Standard Deviation 1 |
| Parent/Caregiver No Pre-visit Prep + Usual Care | Post-Return of Results Mean FACToR Uncertainty Subscale Score | 2.2 score on a scale | Standard Deviation 1.1 |
Secondary
Vital Status at Final f/u
Based on NC Vital Statistics, the child's vital status will be reported as living or deceased.
Time frame: Final follow-up, up to approximately three years after clinic visit 1
Population: Child participants for whom sufficient data was available to determine vital status at follow-up
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Parent/Caregiver Pre-visit Prep + Exome | Vital Status at Final f/u | Deceased | 0 Participants |
| Parent/Caregiver Pre-visit Prep + Exome | Vital Status at Final f/u | Living | 28 Participants |
| Parent/Caregiver Pre-visit Prep + Usual Care | Vital Status at Final f/u | Deceased | 1 Participants |
| Parent/Caregiver Pre-visit Prep + Usual Care | Vital Status at Final f/u | Living | 38 Participants |
| Parent/Caregiver No Pre-visit Prep + Exome | Vital Status at Final f/u | Living | 35 Participants |
| Parent/Caregiver No Pre-visit Prep + Exome | Vital Status at Final f/u | Deceased | 0 Participants |
| Parent/Caregiver No Pre-visit Prep + Usual Care | Vital Status at Final f/u | Living | 36 Participants |
| Parent/Caregiver No Pre-visit Prep + Usual Care | Vital Status at Final f/u | Deceased | 0 Participants |