Pediatric Reporting of Adult-Onset Genomic Results
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| ClinicalTrials.gov Identifier: NCT03832985 |
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Recruitment Status :
Active, not recruiting
First Posted : February 6, 2019
Last Update Posted : July 27, 2023
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Hereditary Breast and Ovarian Cancer Syndrome Lynch Syndrome Familial Hypercholesterolemia | Genetic: Receive an adult-onset result Genetic: Receive a pediatric-onset result Genetic: Control - No Result | Early Phase 1 |
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 pediatric MyCode participants and their parents:
- Group 1 - those with a pathogenic variant in a gene associated with adult onset of disease (n=17 adolescents, 50 parents)
- Group 2 - those with a pathogenic variant in a gene associated with pediatric onset of disease or with risk reduction interventions that begin in childhood (n=53 adolescents, 160 parents)
- Group 3 - those who do not receive a genomic result (n=105 adolescents, 320 parents)
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 (Clinical Trial) |
| Actual Enrollment : | 427 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | The study sample will be drawn from all pediatric MyCode participants (ages 0-17 years). At least one parent will be enrolled for each pediatric participant. Parents of children ages 0-10 years at enrollment will participate in data collection; parents of children ages 11-17 years at enrollment and their children will participate in data collection. Group 3 participants will be frequency matched to Groups 1 and 2 participants on age and sex. Individuals who have already had genetic counseling for any of the MyCode target conditions as part of their routine clinical care will be excluded to avoid confounding study findings. Quantitative data collection will be on 705 (530 parents and 175 adolescents). |
| Masking: | None (Open Label) |
| Masking Description: | No one is prevented from having knowledge of this project. |
| Primary Purpose: | Health Services Research |
| Official Title: | Reporting Adult-Onset Genomic Results to Pediatric Biobank Participants and Parents |
| Actual Study Start Date : | November 25, 2020 |
| Estimated Primary Completion Date : | June 30, 2024 |
| Estimated Study Completion Date : | June 30, 2024 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Receive an adult-onset result
Compare change in psychosocial outcomes and health behaviors of those with a pathogenic variant in a gene associated with adult onset of disease.
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Genetic: Receive an adult-onset result
Assess the psychosocial outcomes and the lived experience of MyCode pediatric participants and parents who have received an adult-onset genomic result. |
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Experimental: Receive a pediatric-onset result
Compare change in psychosocial outcomes and health behaviors of those with a pathogenic variant in a gene associated with pediatric onset of disease or with risk reduction interventions that begin in childhood.
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Genetic: Receive a pediatric-onset result
Assess the psychosocial outcomes and the lived experience of MyCode pediatric participants and parents who have received an adult-onset genomic result. |
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Active Comparator: Control - No result
Compare change in psychosocial outcomes and health behaviors of those without a genomic result.
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Genetic: Control - No Result
Assess the psychosocial outcomes and the lived experience of MyCode pediatric participants and parents who have not received an adult-onset genomic result. |
- The Hospital Anxiety and Depression Scale (HADS) [ Time Frame: Baseline, 1, 6, & 12 months post-disclosure ]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.
- The General Functioning 12-item subscale (GF12) of The McMaster Family Assessment Device (FAD) [ Time Frame: Baseline, 1, 6, & 12 months post-disclosure ]
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)
- Health-Related Quality of Life (HRQOL) [ Time Frame: Baseline, 1, 6, & 12 months post-disclosure ]
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.
- Uptake of cascade testing [ Time Frame: 12 months post-disclosure to pediatric proband ]Uptake of cascade testing (yes/no) among parents.
- Initiation of risk reduction behavior [ Time Frame: 12 months post-disclosure to pediatric proband ]Initiation of risk reduction behavior (yes/no) among parents with familial gene variant.
- Body Image instrument [ Time Frame: Baseline, 1, 6, & 12 months post-disclosure ]Change in adolescents' body image measured using the Body image instrument.
- Self-Esteem Scale [ Time Frame: Baseline, 1, 6, & 12 months post-disclosure ]
The Self-Esteem Scale is made up on 10 items to measure self-esteem. Scoring involves a method of combined ratings. Low self-esteem responses are "disagree" or "strongly disagree" on items 1, 3, 4, 7, 10, and "strongly agree" or "agree" on items 2, 5, 6, 8, 9. Two or three out of three correct responses to items 3, 7, and 9 are scored as one item. One or two out of two correct responses for items 4 and 5 are considered as a single item; items 1,8, and 10 are scored as individual items; and combined correct responses (one or two out of two) to items 2 and 6 are considered to be a single item.
The scale can also be scored by totaling the individual 4-point items after reverse-scoring the negatively worded items.
- Decision Regret scale [ Time Frame: 1 & 12 months post-disclosure ]
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.
- Genetic Counseling Satisfaction Scale (GCSS) [ Time Frame: 1 month post-disclosure ]
The GCSS is a 6-item Likert scale that assesses participant satisfaction with the process and content of genetic counseling. 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 6 items.
- Children's Revised Impact of Events scale [ Time Frame: 1, 6, &12 months post-disclosure ]
The CRIES is a 13-item scale developed as a screening instrument for children at risk of developing PTSD after experiencing a traumatic event. It includes four items measuring intrusion, four items measuring avoidance and five items measuring arousal. Each item is rated on a four-point scale (Not at all, Rarely, Sometimes, Often), scored 0, 1, 3, 5 with no reversed items. The total score indicates the severity of a child's posttraumatic stress reactions with a range from 0 to 65.
A score of 30 and above has been confirmed as the most effective cut-off score for screening cases of PTSD
- Psychological Adaptation to Genetic Information scale (PAGIS) [ Time Frame: 1, 6, & 12 months post-disclosure ]This scale consists of both positively and negatively worded statements that are rated on a 1-6 Likert scale (from 1 for strongly disagree to 6 for strongly agree). The respondent's overall health and health of the affected child (where applicable) is assessed using 5-point likert type items.
- Health Education Impact Questionnaire (heiQ) [ Time Frame: 1, 6, & 12 months post-disclosure ]
The Self-Monitoring and Insight scale captures an individuals' ability to monitor their condition, and their physical and or emotional responses that leads to insight and appropriate action/s to self-manage. It is made up of 7 items, scored by summing item responses and dividing by the number of scale items Scoring is done on a 4-point scale (from 1 for strongly disagree to 4 for strongly agree).
The Health Services Navigation scale aims to capture the positive impact of social engagement and support that evolves through interaction with others and the impact may arise from interaction with others sharing similar health-related life experiences.
It is made up of 5 items, scored by summing item responses and dividing by the number of scale items Scoring is done on a 4-point scale (from 1 for strongly disagree to 4 for strongly agree).
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | Child, Adult, Older Adult |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | Yes |
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03832985
| United States, Pennsylvania | |
| Geisinger | |
| Danville, Pennsylvania, United States, 17822 | |
| Principal Investigator: | Adam H Buchanan, MS, MPH, CGC | Geisinger - Genomic Medicine Institute |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Adam Buchanan, Assistant Professor, Geisinger Clinic |
| ClinicalTrials.gov Identifier: | NCT03832985 |
| Other Study ID Numbers: |
2018-0419 1R01HG009671-01A1 ( U.S. NIH Grant/Contract ) |
| First Posted: | February 6, 2019 Key Record Dates |
| Last Update Posted: | July 27, 2023 |
| Last Verified: | July 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| 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. |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Informed Consent Form (ICF) Analytic Code |
| Time Frame: | Within four weeks of acceptance of the corresponding publication. |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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adult-onset pediatric genomic genetic |
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DNA Repair-Deficiency Disorders Colorectal Neoplasms, Hereditary Nonpolyposis Hereditary Breast and Ovarian Cancer Syndrome Hyperlipoproteinemia Type II Hypercholesterolemia Syndrome Disease Pathologic Processes Ovarian Neoplasms Endocrine Gland Neoplasms Neoplasms by Site Neoplasms Ovarian Diseases Adnexal Diseases Genital Diseases, Female |
Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Urogenital Diseases Genital Neoplasms, Female Urogenital Neoplasms Genital Diseases Endocrine System Diseases Gonadal Disorders Hyperlipidemias Dyslipidemias Lipid Metabolism Disorders Metabolic Diseases Lipid Metabolism, Inborn Errors Metabolism, Inborn Errors Genetic Diseases, Inborn |