Pediatric Reporting of Adult-Onset Genomic Results

Reporting Adult-Onset Genomic Results to Pediatric Biobank Participants and Parents

The Investigators will conduct a longitudinal, mixed-methods cohort study to assess primary and secondary psychosocial outcomes among MyCode adolescent participants and their parents, and health behaviors of children who received an adult- or pediatric-onset genomic result. Data will be gathered via quantitative surveys using validated measures of distress, family functioning, quality of life, body image, perceived cancer/heart disease risk, genetic counseling satisfaction, genomics knowledge, and adjustment to genetic information; qualitative interviews with adolescents and parents; and electronic health records review of children's initiation of risk reduction behaviors. The investigators will also conduct empirical and theoretical legal research to examine the loss of chance doctrine and its applicability to genomic research.

Study Overview

• Status: Completed
• Conditions: Lynch Syndrome; Familial Hypercholesterolemia; Hereditary Breast and Ovarian Cancer Syndrome
• Intervention / Treatment: Genetic: Child(ren) receive an adult-onset result; Genetic: Child(ren) received a pediatric-onset result; Genetic: Control - Negative Result; Genetic: Adolescents who received adult-onset result; Genetic: Adolescents who received a pediatric-onset result; Genetic: Adolescent controls - negative for familial variant

Detailed Description

The Investigators propose a longitudinal, observational cohort study using mixed methods to compare change in psychosocial outcomes and health behaviors among three study groups of MyCode adolescents and three groups of their parents:

1. Group 1 - parents of child(ren) with a pathogenic variant in a gene associated with adult onset of disease
2. Group 2 - parents of child(ren) with a pathogenic variant in a gene associated with pediatric onset of disease or with risk reduction interventions that begin in childhood
3. Group 3 - parents of child(ren) who tested negative for the familial genetic variant
4. Group 4 - adolescents with a pathogenic variant in a gene associated with adult onset of disease
5. Group 5 - adolescents with a pathogenic variant in a gene associated with pediatric onset of disease or with risk reduction interventions that begin in childhood

3. Group 6 - adolescents who tested negative for the familial genetic variant

The Investigators will use the current existing MyCode list of actionable genes designated as actionable by the American College of Medical Genetics and Genomics. Parents of pediatric MyCode participants will be offered the opportunity to participate in the study prior to learning to which group they belong. Consistent with Geisinger policy, children ages 7-17 will be asked to give assent to participate. If a child does not want to assent to participate, he or she will not be enrolled into the study (regardless of their parents' preference regarding enrollment). Parents of children who do not give assent will be ineligible to participate. Parents who decline participation when their child is suspected to have a pathogenic adult-onset result will have their child's sample held for clinical confirmation until the child reaches age 18 years. Parents who decline participation when their child is suspected to have a pathogenic pediatric-onset result will proceed to clinical confirmation of the result and, if confirmed, follow the established clinical return procedure. This recruitment approach is consistent with the MyCode philosophy of notifying participants of actionable findings. Parent-participants will be asked to assess psychosocial outcomes for themselves and for their children. Consistent with co-investigator Angela Bradbury's research on the experience of adolescent girls from families at increased risk for breast cancer, pediatric participants ages 11-17 years at enrollment (i.e., adolescents) will also participate in quantitative surveys and qualitative interviews.

Psychosocial variables such as anxiety and depression will be assessed among parents and adolescents at enrollment (T1), after which those suspected of having a pathogenic variant will proceed to clinical confirmation of that variant. Those whose variant is confirmed clinically as pathogenic or likely pathogenic will then be scheduled for a disclosure appointment. These appointments will be conducted by a genetic counselor and psychologist, who will perform psychosocial assessment, conduct therapeutic consults as needed, and conduct periodic psychosocial assessments of adolescent participants with adult-onset results. Participants with suspected pathogenic variants that are not confirmed clinically and participants without a suspected pathogenic variant will be scheduled for a study visit to notify them of their group status and remind them to follow up with their pediatrician if they have significant personal or family history of cancer or heart disease.

Validated surveys will be used to measure outcomes in each study group at 1 month (T3), 6 months (T4) and 12 months (T5) post-disclosure visit. The investigators will conduct qualitative interviews with a subset of at least 45 participants in each of the two study groups who receive a genomic result to better understand the lived experience of adolescents with an actionable genomic finding and their parents. Data collection will continue after the grant funding ends because of Geisinger Research Division's commitment to following the study cohort. To address the legal specific aim, Dr. Wagner will lead the study team's legal experts in examining and monitoring the loss of chance doctrine in medical malpractice cases in federal and state courts across the United States and in monitoring legislative developments relating to the loss of chance doctrine as it applies to returning adult-onset genomic results to children.

• Study Type: Interventional
• Enrollment (Actual): 162
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822
      • Geisinger

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Any pediatric MyCode participant (ages 0-17) OR
• Parent of a pediatric MyCode participant who has given assent to participate in this study.

Exclusion Criteria:

• Individuals who have already had genetic counseling for any of the actionable target conditions as part of their routine clinical care.
• Individuals who have already had genetic counseling for any of the actionable target conditions through their participation in another research study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1 - Parents of child(ren) who receive an adult-onset result; Compare change in psychosocial outcomes of parents of child(ren) with a pathogenic variant in a gene associated with adult onset of disease.	Genetic: Child(ren) receive an adult-onset result; Assess the psychosocial outcomes and the lived experience of MyCode parents whose child(ren) have received an adult-onset genomic result.
Experimental: Group 2 - Parents of child(ren) who receive a pediatric-onset result; Compare change in psychosocial outcomes among parents of child(ren) with a pathogenic variant in a gene associated with pediatric onset of disease or with risk reduction interventions that begin in childhood.	Genetic: Child(ren) received a pediatric-onset result; Assess the psychosocial outcomes and the lived experience of MyCode parents whose child(ren) have received an pediatric-onset genomic result.
Active Comparator: Group 3 - Parents of child(ren) negative for familial variant; Parents of child(ren) who tested negative for the familial genetic variant	Genetic: Control - Negative Result; Assess the psychosocial outcomes and the lived experience of MyCode parents whose child(ren) tested negative for the familial genetic variant.
Experimental: Group 4 - Adolescents with adult-onset variant; Adolescents with adult-onset genetic variant	Genetic: Adolescents who received adult-onset result; Psychological outcomes among adolescents who received an adult-onset result
Experimental: Group 5 - Adolescents with pediatric-onset variant; Adolescents with pediatric-onset genetic variant	Genetic: Adolescents who received a pediatric-onset result; Psychological outcomes among adolescents who received a pediatric-onset result
Active Comparator: Group 6 - Adolescents negative for familial variant; Adolescents who tested negative for familial genetic variant	Genetic: Adolescent controls - negative for familial variant; Psychological outcomes among adolescents who tested negative for the familial genetic variant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Hospital Anxiety and Depression Scale (HADS) - Anxiety Subscale	The HADS questionnaire is a 14-item scale comprised of seven questions for anxiety and seven questions for depression. Each item is scored from 0-3. The total scoring is as follows: 8-10 = Mild, 11-14 = Moderate, 15-21 = Severe. Scoring for anxiety and depression are to be completed separately. For both scales, a total score of less than 7 indicates non-cases. Total range is 0 (lowest anxiety) - 21 (most severe anxiety).	Baseline
The Hospital Anxiety and Depression Scale (HADS) - Depression Subscale	The HADS questionnaire is a 14-item scale comprised of seven questions for anxiety and seven questions for depression. Each item is scored from 0-3. The total scoring is as follows: 8-10 = Mild, 11-14 = Moderate, 15-21 = Severe. Scoring for anxiety and depression are to be completed separately. For both scales, a total score of less than 7 indicates non-cases. Total range is 0 (lowest) - 21 (most severe).	Baseline
The General Functioning 12-item Subscale (GF12) of The McMaster Family Assessment Device (FAD)	The GF12 subscale is made up of 12 items, six items that reflect healthy family functioning and the other six items reflecting unhealthy functioning. Scoring is on a 4-point scale (from 1 for strongly agree to 4 for strongly disagree) with the scale for the negatively worded items reversed. The total score is then divided by the number of items on the subscale giving a total score ranging from 1.0 (best functioning) to 4.0 (worse functioning)	Baseline
Health-Related Quality of Life (HRQOL)	Healthy days are the positive complementary form of unhealthy days. Healthy days estimates the number of recent days when a person's physical and mental health was good (or better) and is calculated by subtracting the number of unhealthy days from 30 days. Unhealthy days are an estimate of the overall number of days during the previous 30 days when the respondent felt that either his or her physical or mental health was not good. To obtain this estimate, responses to questions 2 and 3 are combined to calculate a summary index of overall unhealthy days, with a logical maximum of 30 unhealthy days. For example, a person who reports 4 physically unhealthy days and 2 mentally unhealthy days is assigned a value of 6 unhealthy days, and someone who reports 30 physically unhealthy days and 30 mentally unhealthy days is assigned the maximum of 30 unhealthy days. Here we report the number and % of participants who reported fair or poor HRQoL.	Baseline
Initiation of Risk Reduction Behavior	Initiation of risk reduction behavior (yes/no) among children with familial gene variant. Not that this is among children of all ages (not just adolescents). Counts are of participants who initiated a risk reduction behavior. Data were collected via chart review for pre-selected risk reduction procedures specific to each genetic condition. Time in months from results disclosure date to date of risk reduction behavior was tracked.	6+ months post-disclosure to pediatric proband
The Hospital Anxiety and Depression Scale (HADS) - Anxiety Subscale	The HADS questionnaire is a 14-item scale comprised of seven questions for anxiety and seven questions for depression. Each item is scored from 0-3. The total scoring is as follows: 8-10 = Mild, 11-14 = Moderate, 15-21 = Severe. Scoring for anxiety and depression are to be completed separately. For both scales, a total score of less than 7 indicates non-cases.Total range is 0 (lowest anxiety) - 21 (most severe anxiety).	1-month post-disclosure
The Hospital Anxiety and Depression Scale (HADS) - Anxiety Subscale	The HADS questionnaire is a 14-item scale comprised of seven questions for anxiety and seven questions for depression. Each item is scored from 0-3. The total scoring is as follows: 8-10 = Mild, 11-14 = Moderate, 15-21 = Severe. Scoring for anxiety and depression are to be completed separately. For both scales, a total score of less than 7 indicates non-cases. Total range is 0 (lowest anxiety) - 21 (most severe anxiety).	6-month post-disclosure
The Hospital Anxiety and Depression Scale (HADS) - Anxiety Subscale	The HADS questionnaire is a 14-item scale comprised of seven questions for anxiety and seven questions for depression. Each item is scored from 0-3. The total scoring is as follows: 8-10 = Mild, 11-14 = Moderate, 15-21 = Severe. Scoring for anxiety and depression are to be completed separately. For both scales, a total score of less than 7 indicates non-cases. Total range is 0 (lowest anxiety) - 21 (most severe anxiety).	12-month post-disclosure
The Hospital Anxiety and Depression Scale (HADS) - Depression Subscale	The HADS questionnaire is a 14-item scale comprised of seven questions for anxiety and seven questions for depression. Each item is scored from 0-3. The total scoring is as follows: 8-10 = Mild, 11-14 = Moderate, 15-21 = Severe. Scoring for anxiety and depression are to be completed separately. For both scales, a total score of less than 7 indicates non-cases. Total range is 0 (lowest) - 21 (most severe).	1-month post-disclosure
The Hospital Anxiety and Depression Scale (HADS) - Depression Subscale	The HADS questionnaire is a 14-item scale comprised of seven questions for anxiety and seven questions for depression. Each item is scored from 0-3. The total scoring is as follows: 8-10 = Mild, 11-14 = Moderate, 15-21 = Severe. Scoring for anxiety and depression are to be completed separately. For both scales, a total score of less than 7 indicates non-cases. Total range is 0 (lowest) - 21 (most severe).	6-month post-disclosure
The Hospital Anxiety and Depression Scale (HADS) - Depression Subscale	The HADS questionnaire is a 14-item scale comprised of seven questions for anxiety and seven questions for depression. Each item is scored from 0-3. The total scoring is as follows: 8-10 = Mild, 11-14 = Moderate, 15-21 = Severe. Scoring for anxiety and depression are to be completed separately. For both scales, a total score of less than 7 indicates non-cases. Total range is 0 (lowest) - 21 (most severe).	12-month post
The General Functioning 12-item Subscale (GF12) of The McMaster Family Assessment Device (FAD)	The GF12 subscale is made up of 12 items, six items that reflect healthy family functioning and the other six items reflecting unhealthy functioning. Scoring is on a 4-point scale (from 1 for strongly agree to 4 for strongly disagree) with the scale for the negatively worded items reversed. The total score is then divided by the number of items on the subscale giving a total score ranging from 1.0 (best functioning) to 4.0 (worse functioning)	1-month post
The General Functioning 12-item Subscale (GF12) of The McMaster Family Assessment Device (FAD)	The GF12 subscale is made up of 12 items, six items that reflect healthy family functioning and the other six items reflecting unhealthy functioning. Scoring is on a 4-point scale (from 1 for strongly agree to 4 for strongly disagree) with the scale for the negatively worded items reversed. The total score is then divided by the number of items on the subscale giving a total score ranging from 1.0 (best functioning) to 4.0 (worse functioning)	6-month post
The General Functioning 12-item Subscale (GF12) of The McMaster Family Assessment Device (FAD)	The GF12 subscale is made up of 12 items, six items that reflect healthy family functioning and the other six items reflecting unhealthy functioning. Scoring is on a 4-point scale (from 1 for strongly agree to 4 for strongly disagree) with the scale for the negatively worded items reversed. The total score is then divided by the number of items on the subscale giving a total score ranging from 1.0 (best functioning) to 4.0 (worse functioning)	12-month post
Health-Related Quality of Life (HRQOL)	Healthy days are the positive complementary form of unhealthy days. Healthy days estimates the number of recent days when a person's physical and mental health was good (or better) and is calculated by subtracting the number of unhealthy days from 30 days. Unhealthy days are an estimate of the overall number of days during the previous 30 days when the respondent felt that either his or her physical or mental health was not good. To obtain this estimate, responses to questions 2 and 3 are combined to calculate a summary index of overall unhealthy days, with a logical maximum of 30 unhealthy days. For example, a person who reports 4 physically unhealthy days and 2 mentally unhealthy days is assigned a value of 6 unhealthy days, and someone who reports 30 physically unhealthy days and 30 mentally unhealthy days is assigned the maximum of 30 unhealthy days. Here we report the number and % of participants who reported fair or poor HRQoL.	1-month post
Health-Related Quality of Life (HRQOL)	Healthy days are the positive complementary form of unhealthy days. Healthy days estimates the number of recent days when a person's physical and mental health was good (or better) and is calculated by subtracting the number of unhealthy days from 30 days. Unhealthy days are an estimate of the overall number of days during the previous 30 days when the respondent felt that either his or her physical or mental health was not good. To obtain this estimate, responses to questions 2 and 3 are combined to calculate a summary index of overall unhealthy days, with a logical maximum of 30 unhealthy days. For example, a person who reports 4 physically unhealthy days and 2 mentally unhealthy days is assigned a value of 6 unhealthy days, and someone who reports 30 physically unhealthy days and 30 mentally unhealthy days is assigned the maximum of 30 unhealthy days. Here we report the number and % of participants who reported fair or poor HRQoL.	6-month post
Health-Related Quality of Life (HRQOL)	Healthy days are the positive complementary form of unhealthy days. Healthy days estimates the number of recent days when a person's physical and mental health was good (or better) and is calculated by subtracting the number of unhealthy days from 30 days. Unhealthy days are an estimate of the overall number of days during the previous 30 days when the respondent felt that either his or her physical or mental health was not good. To obtain this estimate, responses to questions 2 and 3 are combined to calculate a summary index of overall unhealthy days, with a logical maximum of 30 unhealthy days. For example, a person who reports 4 physically unhealthy days and 2 mentally unhealthy days is assigned a value of 6 unhealthy days, and someone who reports 30 physically unhealthy days and 30 mentally unhealthy days is assigned the maximum of 30 unhealthy days. Here we report the number and % of participants who reported fair or poor HRQoL.	12-month post
Revised Children's Anxiety and Depression Scale - Anxiety Subscale	Anxiety subscale of the brief (25-item) version of Revised Children's Anxiety and Depression Scale. Items are scored from 0 (never) to 3 (always) and cumulative scores are converted to T scores per measure guidelines based on participants' school grade and sex. RCADS raw scores were converted to age- and sex-normed T-scores, where a T-score of 48 represents the population mean and the standard deviation is 14 at baseline. T score of greater than or equal to 70 exceeds the clinical threshold (i.e., higher T score = higher anxiety).	baseline
Revised Children's Anxiety and Depression Scale - Anxiety Subscale	Anxiety subscale of the brief (25-item) version of Revised Children's Anxiety and Depression Scale. Items are scored from 0 (never) to 3 (always) and cumulative scores are converted to T scores per measure guidelines based on participants' school grade and sex. RCADS raw scores were converted to age- and sex-normed T-scores, where a T-score of 48 represents the population mean and the standard deviation is 14 at baseline. T score of greater than or equal to 70 exceeds the clinical threshold (i.e., higher T score = higher anxiety).	1-month (T2)
Revised Children's Anxiety and Depression Scale - Anxiety Subscale	Anxiety subscale of the brief (25-item) version of Revised Children's Anxiety and Depression Scale. Items are scored from 0 (never) to 3 (always) and cumulative scores are converted to T scores per measure guidelines based on participants' school grade and sex. RCADS raw scores were converted to age- and sex-normed T-scores, where a T-score of 48 represents the population mean and the standard deviation is 14 at baseline. T score of greater than or equal to 70 exceeds the clinical threshold (i.e., higher T score = higher anxiety).	6-month (T3)
Revised Children's Anxiety and Depression Scale - Anxiety Subscale	Anxiety subscale of the brief (25-item) version of Revised Children's Anxiety and Depression Scale. Items are scored from 0 (never) to 3 (always) and cumulative scores are converted to T scores per measure guidelines based on participants' school grade and sex. RCADS raw scores were converted to age- and sex-normed T-scores, where a T-score of 48 represents the population mean and the standard deviation is 14 at baseline. T score of greater than or equal to 70 exceeds the clinical threshold (i.e., higher T score = higher anxiety).	12-month (T4)
Revised Children's Anxiety and Depression Scale - Depression Subscale	Depression subscale of the brief (25-item) version of Revised Children's Anxiety and Depression Scale. Items are scored from 0 (never) to 3 (always) and cumulative scores are converted to T scores per measure guidelines based on participants' school grade and sex. RCADS raw scores were converted to age- and sex-normed T-scores, where a T-score of 48 represents the population mean and the standard deviation is 14 at baseline. T score of greater than or equal to 70 exceeds the clinical threshold (i.e., higher T score = higher depression).	Baseline
Revised Children's Anxiety and Depression Scale - Depression Subscale	Depression subscale of the brief (25-item) version of Revised Children's Anxiety and Depression Scale. Items are scored from 0 (never) to 3 (always) and cumulative scores are converted to T scores per measure guidelines based on participants' school grade and sex. RCADS raw scores were converted to age- and sex-normed T-scores, where a T-score of 48 represents the population mean and the standard deviation is 14 at baseline. T score of greater than or equal to 70 exceeds the clinical threshold (i.e., higher T score = higher depression).	1-month (T2)
Revised Children's Anxiety and Depression Scale - Depression Subscale	Depression subscale of the brief (25-item) version of Revised Children's Anxiety and Depression Scale. Items are scored from 0 (never) to 3 (always) and cumulative scores are converted to T scores per measure guidelines based on participants' school grade and sex. RCADS raw scores were converted to age- and sex-normed T-scores, where a T-score of 48 represents the population mean and the standard deviation is 14 at baseline. T score of greater than or equal to 70 exceeds the clinical threshold (i.e., higher T score = higher depression).	6-month (T3)
Revised Children's Anxiety and Depression Scale - Depression Subscale	Depression subscale of the brief (25-item) version of Revised Children's Anxiety and Depression Scale. Items are scored from 0 (never) to 3 (always) and cumulative scores are converted to T scores per measure guidelines based on participants' school grade and sex. RCADS raw scores were converted to age- and sex-normed T-scores, where a T-score of 48 represents the population mean and the standard deviation is 14 at baseline. T score of greater than or equal to 70 exceeds the clinical threshold (i.e., higher T score = higher depression).	12-month (T4)
General Functioning 12-item Subscale (GF12) of the McMaster Family Assessment Device (FAD)	The GF12 subscale is made up of 12 items, six items that reflect healthy family functioning and the other six items reflecting unhealthy functioning. Scoring is on a 4-point scale (from 1 for strongly agree to 4 for strongly disagree) with the scale for the negatively worded items reversed. The total score is then divided by the number of items on the subscale giving a total score ranging from 1.0 (best functioning) to 4.0 (worse functioning)	baseline
General Functioning 12-item Subscale (GF12) of the McMaster Family Assessment Device (FAD)	The GF12 subscale is made up of 12 items, six items that reflect healthy family functioning and the other six items reflecting unhealthy functioning. Scoring is on a 4-point scale (from 1 for strongly agree to 4 for strongly disagree) with the scale for the negatively worded items reversed. The total score is then divided by the number of items on the subscale giving a total score ranging from 1.0 (best functioning) to 4.0 (worse functioning)	1-month (T2)
General Functioning 12-item Subscale (GF12) of the McMaster Family Assessment Device (FAD)	The GF12 subscale is made up of 12 items, six items that reflect healthy family functioning and the other six items reflecting unhealthy functioning. Scoring is on a 4-point scale (from 1 for strongly agree to 4 for strongly disagree) with the scale for the negatively worded items reversed. The total score is then divided by the number of items on the subscale giving a total score ranging from 1.0 (best functioning) to 4.0 (worse functioning)	6-month (T2)
General Functioning 12-item Subscale (GF12) of the McMaster Family Assessment Device (FAD)	The GF12 subscale is made up of 12 items, six items that reflect healthy family functioning and the other six items reflecting unhealthy functioning. Scoring is on a 4-point scale (from 1 for strongly agree to 4 for strongly disagree) with the scale for the negatively worded items reversed. The total score is then divided by the number of items on the subscale giving a total score ranging from 1.0 (best functioning) to 4.0 (worse functioning)	12-month (T2)
Health-Related Quality of Life (HRQOL)	Healthy days are the positive complementary form of unhealthy days. Healthy days estimates the number of recent days when a person's physical and mental health was good (or better) and is calculated by subtracting the number of unhealthy days from 30 days. Unhealthy days are an estimate of the overall number of days during the previous 30 days when the respondent felt that either his or her physical or mental health was not good. To obtain this estimate, responses to questions 2 and 3 are combined to calculate a summary index of overall unhealthy days, with a logical maximum of 30 unhealthy days. For example, a person who reports 4 physically unhealthy days and 2 mentally unhealthy days is assigned a value of 6 unhealthy days, and someone who reports 30 physically unhealthy days and 30 mentally unhealthy days is assigned the maximum of 30 unhealthy days. Here we report the number and % of participants who reported fair or poor HRQoL.	1-month (T2)
Health-Related Quality of Life (HRQOL)	Healthy days are the positive complementary form of unhealthy days. Healthy days estimates the number of recent days when a person's physical and mental health was good (or better) and is calculated by subtracting the number of unhealthy days from 30 days. Unhealthy days are an estimate of the overall number of days during the previous 30 days when the respondent felt that either his or her physical or mental health was not good. To obtain this estimate, responses to questions 2 and 3 are combined to calculate a summary index of overall unhealthy days, with a logical maximum of 30 unhealthy days. For example, a person who reports 4 physically unhealthy days and 2 mentally unhealthy days is assigned a value of 6 unhealthy days, and someone who reports 30 physically unhealthy days and 30 mentally unhealthy days is assigned the maximum of 30 unhealthy days. Here we report the number and % of participants who reported fair or poor HRQoL.	6-month (T3)
Health-Related Quality of Life (HRQOL)	Healthy days are the positive complementary form of unhealthy days. Healthy days estimates the number of recent days when a person's physical and mental health was good (or better) and is calculated by subtracting the number of unhealthy days from 30 days. Unhealthy days are an estimate of the overall number of days during the previous 30 days when the respondent felt that either his or her physical or mental health was not good. To obtain this estimate, responses to questions 2 and 3 are combined to calculate a summary index of overall unhealthy days, with a logical maximum of 30 unhealthy days. For example, a person who reports 4 physically unhealthy days and 2 mentally unhealthy days is assigned a value of 6 unhealthy days, and someone who reports 30 physically unhealthy days and 30 mentally unhealthy days is assigned the maximum of 30 unhealthy days. Here we report the number and % of participants who reported fair or poor HRQoL.	12-month (T3)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decision Regret Scale	The Decision Regret Scale is made up of 5 items that address the notion of regret in a variety of ways. Scoring on a 4-point scale (from 1 for strongly agree to 4 for strongly disagree) with the scale for the negatively worded items. The total score is taken from the mean of the 5 items, and then converted to a 0-100 scale by subtracting 1 from each item then multiply by 25. A score of 0 means no regret; a score of 100 means high regret.	1- month post-disclosure
Decision Regret Scale	The Decision Regret Scale is made up of 5 items that address the notion of regret in a variety of ways. Scoring on a 4-point scale (from 1 for strongly agree to 4 for strongly disagree) with the scale for the negatively worded items. The total score is taken from the mean of the 5 items, and then converted to a 0-100 scale by subtracting 1 from each item then multiply by 25. A score of 0 means no regret; a score of 100 means high regret.	12- month post-disclosure

Collaborators and Investigators

• Sponsor: Geisinger Clinic
• Collaborators: National Human Genome Research Institute (NHGRI)
• Investigators: Principal Investigator: Adam H Buchanan, MS, MPH, CGC, Geisinger - Department of Genomic Health

Publications and helpful links

General Publications

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• Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983 Jun;67(6):361-70. doi: 10.1111/j.1600-0447.1983.tb09716.x.
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• DeMarco TA, Peshkin BN, Mars BD, Tercyak KP. Patient satisfaction with cancer genetic counseling: a psychometric analysis of the Genetic Counseling Satisfaction Scale. J Genet Couns. 2004 Aug;13(4):293-304. doi: 10.1023/b:jogc.0000035523.96133.bc.
• Greco LA, Lambert W, Baer RA. Psychological inflexibility in childhood and adolescence: development and evaluation of the Avoidance and Fusion Questionnaire for Youth. Psychol Assess. 2008 Jun;20(2):93-102. doi: 10.1037/1040-3590.20.2.93.
• Bond FW, Hayes SC, Baer RA, Carpenter KM, Guenole N, Orcutt HK, Waltz T, Zettle RD. Preliminary psychometric properties of the Acceptance and Action Questionnaire-II: a revised measure of psychological inflexibility and experiential avoidance. Behav Ther. 2011 Dec;42(4):676-88. doi: 10.1016/j.beth.2011.03.007. Epub 2011 May 25.
• Boterhoven de Haan KL, Hafekost J, Lawrence D, Sawyer MG, Zubrick SR. Reliability and validity of a short version of the general functioning subscale of the McMaster Family Assessment Device. Fam Process. 2015 Mar;54(1):116-23. doi: 10.1111/famp.12113. Epub 2014 Nov 11.
• Moos R, Moos B. Family Environment Scale Manual: Development, Applications, Research. 3rd ed. Palo Alto, CA: Consulting Psychologist Press; 1994
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• Patenaude AF, Dorval M, DiGianni LS, Schneider KA, Chittenden A, Garber JE. Sharing BRCA1/2 test results with first-degree relatives: factors predicting who women tell. J Clin Oncol. 2006 Feb 1;24(4):700-6. doi: 10.1200/JCO.2005.01.7541.
• Gray SW, Martins Y, Feuerman LZ, Bernhardt BA, Biesecker BB, Christensen KD, Joffe S, Rini C, Veenstra D, McGuire AL; CSER Consortium Outcomes and Measures Working Group. Social and behavioral research in genomic sequencing: approaches from the Clinical Sequencing Exploratory Research Consortium Outcomes and Measures Working Group. Genet Med. 2014 Oct;16(10):727-35. doi: 10.1038/gim.2014.26. Epub 2014 Mar 13.
• DuBenske LL, Burke Beckjord E, Hawkins RP, Gustafson DH. Psychometric evaluation of the Health Information Orientation Scale: a brief measure for assessing health information engagement and apprehension. J Health Psychol. 2009 Sep;14(6):721-30. doi: 10.1177/1359105309338892.
• Bradbury AR, Patrick-Miller L, Schwartz LA, Egleston BL, Henry-Moss D, Domchek SM, Daly MB, Tuchman L, Moore C, Rauch PK, Shorter R, Karpink K, Sands CB. Psychosocial Adjustment and Perceived Risk Among Adolescent Girls From Families With BRCA1/2 or Breast Cancer History. J Clin Oncol. 2016 Oct 1;34(28):3409-16. doi: 10.1200/JCO.2015.66.3450. Epub 2016 Aug 22.
• Lupo PJ, Robinson JO, Diamond PM, Jamal L, Danysh HE, Blumenthal-Barby J, Lehmann LS, Vassy JL, Christensen KD, Green RC, McGuire AL; MedSeq Project team. Patients' perceived utility of whole-genome sequencing for their healthcare: findings from the MedSeq project. Per Med. 2016 Jan 1;13(1):13-20. doi: 10.2217/pme.15.45. Epub 2016 Jan 8.
• Schwartz MD, Kaufman E, Peshkin BN, Isaacs C, Hughes C, DeMarco T, Finch C, Lerman C. Bilateral prophylactic oophorectomy and ovarian cancer screening following BRCA1/BRCA2 mutation testing. J Clin Oncol. 2003 Nov 1;21(21):4034-41. doi: 10.1200/JCO.2003.01.088.
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• Kaphingst KA, Facio FM, Cheng MR, Brooks S, Eidem H, Linn A, Biesecker BB, Biesecker LG. Effects of informed consent for individual genome sequencing on relevant knowledge. Clin Genet. 2012 Nov;82(5):408-15. doi: 10.1111/j.1399-0004.2012.01909.x. Epub 2012 Aug 7.
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Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2020
• Primary Completion (Actual): October 31, 2024
• Study Completion (Actual): October 31, 2024

Study Registration Dates

• First Submitted: February 4, 2019
• First Submitted That Met QC Criteria: February 5, 2019
• First Posted (Actual): February 6, 2019

Study Record Updates

• Last Update Posted (Actual): April 9, 2026
• Last Update Submitted That Met QC Criteria: March 20, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: pediatric; genetic; genomic; adult-onset
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Genital Diseases, Female; Endocrine Gland Neoplasms; Colonic Diseases; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Skin Diseases; Breast Diseases; Neoplastic Syndromes, Hereditary; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; DNA Repair-Deficiency Disorders; Breast Neoplasms; Ovarian Neoplasms; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Skin and Connective Tissue Diseases; Hyperlipoproteinemia Type II; Colorectal Neoplasms, Hereditary Nonpolyposis; Hereditary Breast and Ovarian Cancer Syndrome
• Other Study ID Numbers: 2018-0419 (M D Anderson Cancer Center); 1R01HG009671-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

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

IPD Plan Description

As part of his/her responsibilities for the proposed study, the Geisinger Data Broker will work under the guidance of Dr. Kirchner to prepare a cleaned, de-identified copy of each quantitative data set used to support each publication that derives from the study. Data will be stripped of identifiers according to the Safe Harbor method of de-identification (https://www.hhs.gov/hipaa/for-professionals/privacy/special-topics/de-identification/index.html).

These data and related information (participant flow, baseline characteristics, outcome measures and statistical analyses) will then be uploaded to ClinicalTrials.gov within four weeks of acceptance of the corresponding publication. If applicable, the Data Broker will work with the project manager to upload data on adverse events to ClinicalTrials.gov on the same time schedule.

• IPD Sharing Time Frame: Within four weeks of acceptance of the corresponding publication.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No