Pediatric Reporting of Adult-Onset Genomic Results

Familial Hypercholesterolemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03832985
• Other study ID #: 2018-0419
• Secondary ID: 1R01HG009671-01A
• Status: Active, not recruiting
• Phase: Early Phase 1
• Start date: November 25, 2020
• Est. completion date: June 30, 2024

Study information

• Verified date: July 2023
• Source: Geisinger Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The Investigators will conduct a longitudinal, mixed-methods cohort study to assess primary and secondary psychosocial outcomes among 705 MyCode pediatric participants and their parents, and health behaviors of parents whose children receive 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 parents' cascade testing uptake and 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.

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 pediatric MyCode participants and their parents: 1. Group 1 - those with a pathogenic variant in a gene associated with adult onset of disease (n=17 adolescents, 50 parents) 2. 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) 3. 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 427
• Est. completion date: June 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Neoplasms, Hereditary Nonpolyposis
• Familial Hypercholesterolemia
• Hereditary Breast and Ovarian Cancer Syndrome
• Hypercholesterolemia
• Hyperlipoproteinemia Type II
• Lynch Syndrome
• Syndrome

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	Geisinger	Danville	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Geisinger Clinic	National Human Genome Research Institute (NHGRI)

Country where clinical trial is conducted

United States, 

References & Publications (24)

Bjelland I, Dahl AA, Haug TT, Neckelmann D. The validity of the Hospital Anxiety and Depression Scale. An updated literature review. J Psychosom Res. 2002 Feb;52(2):69-77. doi: 10.1016/s0022-3999(01)00296-3. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Brehaut JC, O'Connor AM, Wood TJ, Hack TF, Siminoff L, Gordon E, Feldman-Stewart D. Validation of a decision regret scale. Med Decis Making. 2003 Jul-Aug;23(4):281-92. doi: 10.1177/0272989X03256005. — View Citation

Buchanan AH, Voils CI, Schildkraut JM, Fine C, Horick NK, Marcom PK, Wiggins K, Skinner CS. Adherence to Recommended Risk Management among Unaffected Women with a BRCA Mutation. J Genet Couns. 2017 Feb;26(1):79-92. doi: 10.1007/s10897-016-9981-6. Epub 2016 Jun 6. — View Citation

CDC. Office of Public Health Genomics - Genomic Tests and Family History by Levels of Evidence.2014; http://www.cdc.gov/genomics/gtesting/tier.htm.

Chew LD, Bradley KA, Boyko EJ. Brief questions to identify patients with inadequate health literacy. Fam Med. 2004 Sep;36(8):588-94. — View Citation

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. — View Citation

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. — View Citation

Giannopoulou I, Smith P, Ecker C, Strouthos M, Dikaiakou A, Yule W. Factor structure Children's Revised Impact of Events (CRIES) Scale with children exposed to earthquake Pers Individ Diff. 2006;40(5):1027-1037

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. — View Citation

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. — View Citation

Green ED, Guyer MS; National Human Genome Research Institute. Charting a course for genomic medicine from base pairs to bedside. Nature. 2011 Feb 10;470(7333):204-13. doi: 10.1038/nature09764. — View Citation

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. — View Citation

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. — View Citation

McDermott E, Moloney J, Rafter N, Keegan D, Byrne K, Doherty GA, Cullen G, Malone K, Mulcahy HE. The body image scale: a simple and valid tool for assessing body image dissatisfaction in inflammatory bowel disease. Inflamm Bowel Dis. 2014 Feb;20(2):286-90. doi: 10.1097/01.MIB.0000438246.68476.c4. — View Citation

Moos R, Moos B. Family Environment Scale Manual: Development, Applications, Research. 3rd ed. Palo Alto, CA: Consulting Psychologist Press; 1994

Osborne RH, Elsworth GR, Whitfield K. The Health Education Impact Questionnaire (heiQ): an outcomes and evaluation measure for patient education and self-management interventions for people with chronic conditions. Patient Educ Couns. 2007 May;66(2):192-201. doi: 10.1016/j.pec.2006.12.002. Epub 2007 Feb 22. — View Citation

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. — View Citation

Read CY, Perry DJ, Duffy ME. Design and psychometric evaluation of the Psychological Adaptation to Genetic Information Scale. J Nurs Scholarsh. 2005;37(3):203-8. doi: 10.1111/j.1547-5069.2005.00036.x. — View Citation

Rosenberg M. Society and the adolescent self-image. Princeton, NJ: Princeton University Press; 1965

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. — View Citation

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. — View Citation

* Note: There are 24 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Hospital Anxiety and Depression Scale (HADS)	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.	Baseline, 1, 6, & 12 months post-disclosure
Primary	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, 1, 6, & 12 months post-disclosure
Primary	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.	Baseline, 1, 6, & 12 months post-disclosure
Primary	Uptake of cascade testing	Uptake of cascade testing (yes/no) among parents.	12 months post-disclosure to pediatric proband
Primary	Initiation of risk reduction behavior	Initiation of risk reduction behavior (yes/no) among parents with familial gene variant.	12 months post-disclosure to pediatric proband
Secondary	Body Image instrument	Change in adolescents' body image measured using the Body image instrument.	Baseline, 1, 6, & 12 months post-disclosure
Secondary	Self-Esteem Scale	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.	Baseline, 1, 6, & 12 months post-disclosure
Secondary	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.	1 & 12 months post-disclosure
Secondary	Genetic Counseling Satisfaction Scale (GCSS)	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.	1 month post-disclosure
Secondary	Children's Revised Impact of Events scale	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	1, 6, &12 months post-disclosure
Secondary	Psychological Adaptation to Genetic Information scale (PAGIS)	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.	1, 6, & 12 months post-disclosure
Secondary	Health Education Impact Questionnaire (heiQ)	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).	1, 6, & 12 months post-disclosure