Reasons, Hopes, Risks, Expectations

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9/19/2018

Reasons, Hopes, Risks, Expectations:  Qualitative Interviews of Parents  Consenting to Genomic Sequencing for  their Child Jami Gattuso, Liza Johnson, Michele Pritchard, Breya Walker, Kayla Hamilton,  Jessica Valdez, Belinda Mandrell, Kim Nichols Division of Nursing Research  Division of Cancer Predisposition St. Jude Children’s Research Hospital

• Jami Gattuso has nothing to disclose

Learning Outcome • After this session the learner will be able to  recall reasons, risks, benefits,  hopes/expectations reported by parents who  enroll their child in a germline sequencing  study

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G4K Study Objectives Primary Objectives

Exploratory Objectives

• To perform clinical next generation • To generate and analyze data  whole genome  (WGS), exome  describing the informed consent  (WES), and RNA sequencing on St.  process and patient/parent  Jude pediatric oncology patients  perceptions of genomic  prospectively over a 24 month  investigations and research. period • To generate and analyze data  • To use WGS, WES and RNA  describing the return of genomic  sequence data to identify and  sequencing results, examine  characterize somatic genetic  variants of pathological significance  patient/parent understanding of  these results and assess the impact  and germline genetic variants  of results on patients and families. associated with increased cancer  risk.

Background • Rapid growth in cancer care • Unfamiliar/complex for patients and families • 8.5‐12% of pediatric oncology patients will have a germline  cancer predisposition gene • Limited understanding of risk • Potential negative psychological effects • Difficult distinction between standard care and research • Why do parents AGREE to participate? What do they understand?

G4K Study flowchart Identify Eligible Participants Study Introduction Visit Informed Consent Conversation (ICC) Consent for Genomic Studies? Yes

Consent for Interviews, Surveys? No

Obtain Tumor/Germline DNA/RNA

Consent to Receive Germline Results? No

No

Yes

ICC Follow-up Visit

Yes

Complete WES, WGS, RNA Sequencing

Return of Results Visit

Data Analysis/Variant Interpretation

Return of Results Follow-up Visit

Generate Reports Tumor

Germline

Place in EMR/Discuss with Doctor

Place in EMR/Discuss with Doctor

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Open‐Ended Interview Questions • • • •

Understanding Decision‐making  Informed consent conversation Study process/educational brochure

Selected Open‐Ended Questions • Can you tell me in your own words what the  Genomes4Kids (G4K) study is about? • The study will examine the genes in your child’s  cancer cells and healthy cells. What is your  understanding of why this is being done?

• What do you remember from talking with the  study nurse about this research study? • Did you talk to your child about taking part in  this study?  Tell me about your child’s part in  the decision process

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• Have you talked about this study with any family  members, your doctor or genetic counselor? Tell  me more about those conversations. Did talking  with them influence your decision?

Reasons, Hopes, Risks, Expectations • Families have many different reasons for taking part in  research studies.  Please share with us your reasons for your  decision to participate or not participate in G4K. • What risks, if any, are involved with taking part in G4K? • What benefits, if any, are involved with taking part in G4K? • What type of information do you expect or hope to learn from  taking part in this study?

Sample • Convenience sample • Parents of children/AYAs with a cancer diagnosis • Being treated at St. Jude Children’s Research  Hospital • 31 parents representing 31 patients • All agreed to participate in the genomic sequencing • All agreed to interviews

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Sample  • •

27 Newly diagnosed 4 Relapsed

• • •

11 Leukemia/lymphoma 9 Solid tumor 11 Brain tumor

• • • •

23 White 4 Black 3 Asian 1 Black/White

Interviews • In‐person • Within the first month after Informed Consent Conversation • Various locales at the hospital • Conducted by 2 trained interviewers  • September, 2015‐April , 2017 • 9‐52 minutes (median 16.5) • Audio‐recorded • Transcribed

Analysis • MAXQDA program was used • Content Analysis • Themes were derived from the data • Joint coding by team of 5 study members • One code occurrence was noted no matter if  parent mentioned once or multiple times

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Perceptions of  What the Study is About • Basic concept of the study of Genetics (n=23) • To determine if this child’s cancer is Hereditary and if other family members will be at risk (n=17) • To determine the Etiology of the child’s cancer  (n=16)

“why it happens in the first place”

Why Examine Genes from Both  Cancer and Healthy Cells • Etiology (n=11) • Understanding of the concept of Somatic versus Germline (n=11) • Not grasp the concept of why this comparison is being done (n=7) • Hereditary (n=6) • Other, less frequent codes—determine chance for future relapse or  new cancer, to target treatment for the child’s cancer 

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What Was Remembered from the Informed  Consent Conversation • Hereditary (n=11) • That this is a Research study (n=11) • That it is Voluntary (n=7) • To determine any Proactive measures (health behaviors,  monitoring) that could be preventative (n=6) • That the information was Well explained (n=6)

What Risks, if any • Parents recalled risks were explained, but DO NOT  perceive any risk to apply to their family (n=18) • The Findings (n=9) (mutation will be found OR nothing  will be found) • Insurance issues (n=7) • No extra blood draw (n=6) • Only 1 parent expressed they were Unsure of any risks  involved

What Benefits, if any • • • •

Altruism (n=21) Knowledge about the child’s disease (n=14) Hereditary (n=13) Proactive (n=10)

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“I imagine the first benefit is the fact that it will help the researchers,  you know, to know exactly why or try to identify why it happens to  children, possibly shorten the treatment, or get tailored treatment of  each person, especially the fact that it’s for the future, not because  it’s going to happen for him now.  If a family does know that they are  predisposed to such diseases or such cancers, they might take some  precautions, they think, it’s something that’s preventable, you know.   That is why I said that I signed up for the whole hog, I’m like, if you’re  going to tell me the rest of the results, that’s fine.  I would love to  know.  The other benefits, of course, he might just gain something  from this but I don’t know so but That would be super, that would be  lovely yeah...  I think that’s basically it.”

Reasons for Participation • • • • •

Altruism (n=21) Hereditary (n=10) Knowledge (n=10) To Contribute to Research (n=7) Proactive (n=6)

“I mean, like, just with any research here at the hospital, I think it will help, you know, for other patient’s that maybe have the same tumor as well, and you know, just maybe, I don’t know. I feel like it will help with research”

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Expectations/Hopes  • • • • • •

Hereditary (n=8) Proactive (n=7) Hope to find NOTHING (n=5) Want to know Risk for future cancers (n=5) General Knowledge (n=5) Tailor treatment for their child (actionable  findings) (n=5)

Conclusions/Implications • Families want to know the CAUSE • Dual issue of wanting to know but being afraid  of what will be found (or finding nothing) • Although risks are well explained, parents don’t  see those as applying to them • Some have a grasp on the complex nature of  genomic sequencing studies

NEXT STEPS!!! Primary Objectives • To perform clinical next generation whole genome  (WGS), exome (WES),  and RNA sequencing on St. Jude  pediatric oncology patients  prospectively over a 24 month period

• To use WGS, WES and RNA sequence data to identify and characterize  somatic genetic variants of  pathological significance and germline  genetic variants associated with  increased cancer risk.

Exploratory Objectives • To generate and analyze data  describing the informed consent  process and patient/parent  perceptions of genomic investigations  and research. • To generate and analyze data  describing the return of genomic  sequencing results, examine  patient/parent understanding of these  results and assess the impact of results  on patients and families.

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“With her particular condition, which is very rare for her age, and very rare the type that she has, any study that can expound on that is going to be beneficial to other people in the study. I think she's like the 25th person in the world to have this particular type. So, we wholeheartedly want to help, but as well, she has three siblings that may be affected somewhere down the road. So, if we can identify it earlier, since they are younger siblings, that would benefit them as well as other children, surely.”

Genomes for Kids (G4K)

Selected References • Meiser B. Psychological impact of genetic testing for cancer  susceptibility: an update of the literature. Psychooncology, 14:10‐ 60‐74, 2005 • Angiolillo AL, Simon C, Kodish E et al. Staged informed consent for  a randomized clinical trils and childhood leukemia: impact on the  consent process. Pediatric Blood Cancer, 42:433‐7, 2004 • Cousino M, Hazen R, Yamokoski A et al. Parent participation and  physician‐parent communication during informed consent in child  leukemia. Pediatrics, 128: e1544‐51, 2011

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