Clinical trial NCT03832985: Pediatric Reporting of Adult-Onset Genomic Results
Official title: Reporting Adult-Onset Genomic Results to Pediatric Biobank Participants and Parents
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Hereditary Breast and Ovarian Cancer Syndrome
Lynch Syndrome
Familial Hypercholesterolemia
Keywords: adult-onset
pediatric
genomic
genetic
Lead sponsor: Geisinger Clinic
Sponsor class: OTHER
Collaborators: name: National Human Genome Research Institute (NHGRI)
First posted: 2019-02-06
Enrollment: 427
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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).
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief 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.

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 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.

Eligibility criteria: 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.

Primary outcomes:
measure: The Hospital Anxiety and Depression Scale (HADS)
timeFrame: Baseline, 1, 6, & 12 months post-disclosure
measure: The General Functioning 12-item subscale (GF12) of The McMaster Family Assessment Device (FAD)
timeFrame: Baseline, 1, 6, & 12 months post-disclosure
measure: Health-Related Quality of Life (HRQOL)
timeFrame: Baseline, 1, 6, & 12 months post-disclosure
measure: Uptake of cascade testing
timeFrame: 12 months post-disclosure to pediatric proband
measure: Initiation of risk reduction behavior
timeFrame: 12 months post-disclosure to pediatric proband
Secondary outcomes:
measure: Body Image instrument
timeFrame: Baseline, 1, 6, & 12 months post-disclosure
measure: Self-Esteem Scale
timeFrame: Baseline, 1, 6, & 12 months post-disclosure
measure: Decision Regret scale
timeFrame: 1 & 12 months post-disclosure
measure: Genetic Counseling Satisfaction Scale (GCSS)
timeFrame: 1 month post-disclosure
measure: Children's Revised Impact of Events scale
timeFrame: 1, 6, &12 months post-disclosure
measure: Psychological Adaptation to Genetic Information scale (PAGIS)
timeFrame: 1, 6, & 12 months post-disclosure
measure: Health Education Impact Questionnaire (heiQ)
timeFrame: 1, 6, & 12 months post-disclosure
Other outcomes:
Locations:
city: Danville
country: United States
facility: Geisinger
state: Pennsylvania
Study officials:
affiliation: Geisinger - Department of Genomic Health
name: Adam H Buchanan, MS, MPH, CGC
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.
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.
citation: Moos R, Moos B. Family Environment Scale Manual: Development, Applications, Research. 3rd ed. Palo Alto, CA: Consulting Psychologist Press; 1994
citation: Rosenberg M. Society and the adolescent self-image. Princeton, NJ: Princeton University Press; 1965
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.
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.
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.
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.
citation: 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.
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.
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.
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.
citation: 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.
citation: Chew LD, Bradley KA, Boyko EJ. Brief questions to identify patients with inadequate health literacy. Fam Med. 2004 Sep;36(8):588-94.
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.
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.
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
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.
citation: 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.
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.
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.
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.
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.
citation: Savatt JM, Wagner JK, Joffe S, Rahm AK, Williams MS, Bradbury AR, Davis FD, Hergenrather J, Hu Y, Kelly MA, Kirchner HL, Meyer MN, Mozersky J, O'Dell SM, Pervola J, Seeley A, Sturm AC, Buchanan AH. Pediatric reporting of genomic results study (PROGRESS): a mixed-methods, longitudinal, observational cohort study protocol to explore disclosure of actionable adult- and pediatric-onset genomic variants to minors and their parents. BMC Pediatr. 2020 May 15;20(1):222. doi: 10.1186/s12887-020-02070-4.