Transcript Experiences of Children Enrolled in Pediatric Oncology Research: Implications for Assent Yoram Unguru, MD, MS, MA The Herman & Walter Samuelson Children’s Hospital at.

Experiences of Children Enrolled
in Pediatric Oncology Research:
Implications for Assent
Yoram Unguru, MD, MS, MA
The Herman & Walter Samuelson Children’s Hospital at Sinai
Division of Pediatric Hematology/Oncology
Johns Hopkins University - Berman Institute of Bioethics
DISCLOSURES

None
"The good parent does not just nurture to
a point of maturation: he is expected to
inhibit self-destructive impulses; he is
expected to substitute his superior
judgment for the short vision of the child;
he is expected to use education,
persuasion, seduction, and even force and
coercion when necessary in the service of
producing a healthy and independent
adult."
Gaylin W. Competence: No longer all or none. In: Gaylin W and
Macklin R eds. Who speaks for the Child: The problems of proxy
consent. New York: Plenum Press; 1982, 31.
BACKGROUND

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Research is a cornerstone of modern
medicine
Research agenda is the sine qua non of
pediatric cancer
Cancer clinical research trials

Children >>>>> Adults
BACKGROUND
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*
Pediatric clinical trials are complex
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Therapeutic misconception
WHY IS ASSENT AN
IMPORTANT TOPIC?
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Birth of assent
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History of assent
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National Commission + Belmont Report
American Academy of Pediatrics
BELMONT
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“Because the subject's ability to understand is a
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“Investigators are responsible for ascertaining
function of intelligence, rationality, maturity and
language, it is necessary to adapt the presentation of
the information to the subject's capacities.”
that the subject has comprehended the
information.”

National Commission for the Protection of Human Subjects of Biomedical and
Behavioral Research. (1979). The Belmont Report: Ethical Principles and Guidelines for
the Protection of Human Subjects of Research. Washington, DC: US Government
Printing Office.
AAP

“[Make] a clinical assessment of [the]
patient’s understanding of the situation and
the factors influencing how he or she is
responding, including whether there is
inappropriate pressure to accept testing or
therapy.”

Committee on Bioethics, American Academy of Pediatrics. Informed
consent, parental permission, and assent in pediatric practice.
Pediatrics 1995;95:314-317.
BACKGROUND
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Subpart D of 45 CFR 46 governs pediatric research
(1983)
Assent

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“A child’s affirmative agreement to participate in research.
Mere failure to object should not, absent affirmative
agreement, be construed as assent”
IRBs
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“shall determine that adequate provisions are made for
soliciting the assent of the children, when in the judgment of
the IRB the children are capable of providing assent”
PROBLEMS
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Vague and unclear
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Problems with CFR definition of assent
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No specific age limit
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Onus is on IRB
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Flexible, yet fail to enumerate what is required with too little
guidance as to what constitutes a meaningful concept of
assent
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
Kimberely, et al. Variation in Standards of Research Compensation and Child Assent Practices: A Comparison of 69
Institutional Review Board-Approved Informed Permission and Assent Forms for 3 Multicenter Pediatric Clinical
Trials. Pediatrics 2006;117:1706-1711.
Whittle, et al. Institutional Review Board Practices Regarding Assent in Pediatric Research. Pediatrics
2004;113:1747-1752.
MORE PROBLEMS

Assent in 2009

No consensus

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Government, Prof associations, Assent community
Definition
Age
Participants
Conflict resolution
Assent vs consent
Disclosure
Children’s desires
Assessment
Decision-making model
ASSENT  CONSENT

Children’s Views on Their Involvement in
Clinical Research
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Chappuy H, et al. Ped Blood & Cancer 2008;50:1043-1046
“To examine the level of children’s understanding of
informed consent in clinical trials & factors that
may influence these processes”
“Determine children’s understanding of 9 items
required in the informed consent document”
*
ASSENT IN 2009
ASSENT IN 2007
BACKGROUND
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Components of valid assent
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Determine children’s understanding
Preferences for involvement
Children & the therapeutic misconception
METHODS
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Sample

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7-18 year olds with cancer who have
assented to therapeutic clinical trials
Survey instrument (QuAs)

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Closed-ended
Open-ended
METHODS
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Eligibility criteria
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Sixty-two children
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Documented malignancy
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Age 7-18 years
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Assented to a COG / PBTC research protocol
METHODS
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Study Procedure
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Semi-structured, private, face-to-face, audio-recorded
interviews
Respondents were given a questionnaire identical to the one
used by the investigator
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Questions were read aloud & children responded orally
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Prompts were included to assure understanding
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Interviews were transcribed verbatim & verified against the
audiotape
CHILDREN’S UNDERSTANDING &
PREFERENCES for RESEARCH
INVOLVEMENT
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Research
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Decision-making
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Familiarity
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Decisional priority
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Knowledge
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Types of decisions
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Awareness
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Role in decision to enroll
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Understanding
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Preferences / Perceptions
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Appreciation
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Suggestions
FAMILIARITY &
KNOWLEDGE of RESEARCH
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Research term
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Study
Research
Protocol
Experimental
Trial
Enrollment
Randomization
Consent
Assent
Knowledge of research
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Familiarity + being told about different ways to tx illness
AWARENESS of RESEARCH
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Know tx is considered clinical research
Main reason for study participation is to improve care for future
children with cancer
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One reason for study participation is to determine effect(s) of tx(s)
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Prior to starting tx, signed name to a form
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Know that signing name means agreed to participate in a study
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Read form
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Child / Parent received copy of signed form
UNDERSTANDING of
RESEARCH
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One reason my doctor is giving me the medicines (s)he is, is to compare (figure
out) the effects (good & bad) of 2 or more different ways of treating other
children who have the same type of illness as mine to see which is better
The treatment I get/got as part of the clinical research was chosen randomly
(by chance, like flipping a coin) from 2 or more options
Compared to other treatment for my illness, my study does not have more risks
or discomforts (bad things) associated with it
It is proven that the medicines I am getting are the best treatment for my type
of illness
By being part of the study, I am helping my doctor learn about my illness &
ways to help kids who will get sick like me in the future
I can withdraw (not be part of) from the study anytime my parents or I decide
to withdraw
APPRECIATION of
RESEARCH
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Why did you decide to participate in a clinical
research study?
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My parents told me to
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My doctor told me to
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My parents & doctor told me to
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To get better
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To help other children
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To help my doctor learn more about illness
DECISION-MAKING
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Decisional priority
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Types of decisions
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Very large, Large, Little, Very little, None
Preferences / Perceptions
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Major or minor
Role in decision to enroll
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Children’s overall involvement in decisions
Info, peer discussions, inclusion in decisions
Suggestions
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For improving their role in decision-making
Characteristic
Number
Percentage
16
21
43
57
8
8
9
12
22
22
24
32
11
3
8
6
3
3
2
1
30
8
22
16
8
8
5
3
2
1
1
6
26
1
5
3
3
16
70
3
11
7
14
5
30
19
38
13
23
14
62
38
Gender
Male
Female
Age (years)
Males <14
Males >14
Females <14
Females >14
Cancer diagnosis
ALL
AML
CNS
HD
NHL
GCT
Osteosarcoma
Ewing
Research protocol (phase)
Pilot
Phase I
Phase I/II
Phase II
Phase III
Biology
Months since protocol enrollment
<4
4-12
12-24
>24
Treatment
Ongoing
Completed
RESULTS
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Children
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Unaware their treatment is clinical research
Limited understanding of research *
Do not understand MD’s explanation *
Personal gain + Altruism *
Pressured to enroll *
Exclusion versus inclusion *
Reluctant to discuss decision-making *
Types of decisions – Minor
Want to make decisions
Desire parental + MD role *
Interested in research
Children’s Familiarity with Research Terminology, Research Knowledge, & Elements Comprising Awareness of Research Enrollment (n = 37)
FAMILIARITY (whether recall having heard items #1-9)
Research term
No.
% “Familiar”
1.
Study
35
95
2.
Research
32
87
3.
Consent
25
68
4.
Protocol
24
65
5.
Experimental
21
57
6.
Trial
15
41
7.
Enrollment
13
35
8.
Assent
12
32
9.
Randomization
7
19
No.
26
%
“yes”
70
No.
%
Answering
“yes” or correct
response†
KNOWLEDGE (Sum of responses to 9 familiarity items + response to item #10)
10. Before starting treatment, did your doctor meet with you to talk about the ways to treat your illness?
AWARENESS
1.
Main reason for study participation is to improve care for future children with cancer
33
89†
2.
One reason for study participation is to determine effect(s) of treatment(s)
33
89†
3.
Prior to starting treatment, signed name to a form
21
57
4.
Child / Parent received copy of signed form
21
57
5.
Read form
20
54
6.
Know that signing name means agreed to participate in study
19
51
7.
Know treatment is considered clinical research
18
49
Answering
RESULTS
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HD & GCT greater knowledge (mean=7.6) than “others”
(mean=5.0)
HD, CNS, leukemia higher mean understanding (7.8, 7.5, 6.8)
than “others” (mean 6.0)
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Controlling for age, neither remained sig, p=0.38, p=0.22
Knowledge, awareness, understanding, & appreciation of
research were not significantly associated with gender, protocol
phase or type, months since diagnosis, or ongoing versus
completed treatment
HD, GCT, leukemia significantly greater awareness (mean=5.5)
& appreciation (mean=2.2) than “others” (mean 3.6 & 1.0)
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Remained significant when controlling for age, p=0.019, p<0.001
CHILDREN’S SUGGESTIONS for
IMPROVEMENT
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“Talk to me (too)”
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No “medicalese”
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“Don’t assume”
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Be honest / truthful
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More choices / details
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“Don’t focus on my age”
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Offer advice
DISCUSSION
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Irrespective of age, children with HD, GCT, &
leukemia had sig greater awareness &
appreciation of research (p=0.019, p<0.001)
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?Outcome-related
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?Altruism
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Decisional priority + Pressure to enroll
LIMITATIONS
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Single investigator-single institution, pilot study
Responses may not reflect actual beliefs, but
what children think investigators want them to
say
Interviews occurred after children had assented
to research enrollment
Findings reflect reports of children only
IMPLICATIONS
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Clinical trials
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Gold standard in pediatric heme/onc
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Improve understanding
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Greater decision-making role
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When appropriate
Present me with more choices for treatment in the
beginning. [Things like] Facts & previous outcomes from
treatments they've given. I know decisions sometimes are
needed in a short amount of time, but sometimes you need a
little time to think about what's going to happen - at least
just ask. Just because I am deemed a child because I'm less
than 18, I don't think I should be treated like a full child
when it comes to my health . . . I need doctors' advice, but
sometimes I want to decide & not be written off & treated
like a child because I'm under 18
–17 year-old
LET ASSENT OUT ITS CAGE