experiences of children enrolled in pediatric oncology
TRANSCRIPT
Experiences of Children Enrolled in Pediatric Oncology Research: Implications for Assent
Yoram Unguru, MD, MS, MAThe 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
Research is a cornerstone of modern medicine
Research agenda is the sine qua non of pediatric cancer
Cancer clinical research trials Children >>>>> Adults
BACKGROUND
Pediatric clinical trials are complex
Therapeutic misconception
WHY IS ASSENT AN IMPORTANT TOPIC? Birth of assent
History of assent National Commission + Belmont
Report American Academy of Pediatrics
BELMONT “Because the subject's ability to understand is a
function of intelligence, rationality, maturity and language, it is necessary to adapt the presentation of the information to the subject's capacities.”
“Investigators are responsible for ascertaining 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 Subpart D of 45 CFR 46 governs pediatric
research (1983)
Assent “A child’s affirmative agreement to participate in
research. Mere failure to object should not, absent affirmative agreement, be construed as assent”
IRBs “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 Vague and unclear
Problems with CFR definition of assent No specific age limit
Onus is on IRB
Flexible, yet fail to enumerate what is required with too little guidance as to what constitutes a meaningful concept of assent
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 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 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 2007
ASSENT IN 2009
BACKGROUND Components of valid assent
Determine children’s understanding Preferences for involvement
Children & the therapeutic misconception
METHODS
Sample 7-18 year olds with cancer who have
assented to therapeutic clinical trials
Survey instrument (QuAs) Closed-ended Open-ended
METHODS Eligibility criteria
Sixty-two children
Documented malignancy
Age 7-18 years
Assented to a COG / PBTC research protocol
METHODS Study Procedure
Semi-structured, private, face-to-face, audio-recorded interviews
Respondents were given a questionnaire identical to the one used by the investigator
Questions were read aloud & children responded orally
Prompts were included to assure understanding
Interviews were transcribed verbatim & verified against the audiotape
CHILDREN’S UNDERSTANDING & PREFERENCES for RESEARCH INVOLVEMENT
Research Familiarity
Knowledge
Awareness
Understanding
Appreciation
Decision-making Decisional priority
Types of decisions
Role in decision to enroll
Preferences / Perceptions
Suggestions
FAMILIARITY & KNOWLEDGE of RESEARCH Research term
Study Research Protocol Experimental Trial Enrollment Randomization Consent Assent
Knowledge of research Familiarity + being told about different ways to tx illness
AWARENESS of RESEARCH Know tx is considered clinical research
Main reason for study participation is to improve care for future children with cancer
One reason for study participation is to determine effect(s) of tx(s)
Prior to starting tx, signed name to a form
Know that signing name means agreed to participate in a study
Read form
Child / Parent received copy of signed form
UNDERSTANDING of RESEARCH 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 Why did you decide to participate in a clinical
research study? My parents told me to
My doctor told me to
My parents & doctor told me to
To get better
To help other children
To help my doctor learn more about illness
DECISION-MAKING Decisional priority
Children’s overall involvement in decisions
Types of decisions Major or minor
Role in decision to enroll Very large, Large, Little, Very little, None
Preferences / Perceptions Info, peer discussions, inclusion in decisions
Suggestions For improving their role in decision-making
Characteristic Number Percentage
Gender Male Female
1621
4357
Age (years) Males <14 Males >14 Females <14 Females >14
88912
22222432
Cancer diagnosis ALL AML CNS HD NHL GCT Osteosarcoma Ewing
113863321
30822168853
Research protocol (phase) Pilot Phase I Phase I/II Phase II Phase III Biology
2116261
53316703
Months since protocol enrollment < 4 4-12 12-24 >24
117145
30193813
Treatment Ongoing Completed
2314
6238
RESULTS Children
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
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
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?
No.26
% Answering “yes”70
AWARENESS
No. % Answering “yes” or correct response†
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
Children’s Familiarity with Research Terminology, Research Knowledge, & Elements Comprising Awareness of Research Enrollment (n = 37)
RESULTS 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)
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)
Remained significant when controlling for age, p=0.019, p<0.001
CHILDREN’S SUGGESTIONS for IMPROVEMENT
“Talk to me (too)”
No “medicalese”
“Don’t assume”
Be honest / truthful
More choices / details
“Don’t focus on my age”
Offer advice
DISCUSSION Irrespective of age, children with HD,
GCT, & leukemia had sig greater awareness & appreciation of research (p=0.019, p<0.001) ?Outcome-related
?Altruism
Decisional priority + Pressure to enroll
LIMITATIONS 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
Clinical trials Gold standard in pediatric heme/onc
Improve understanding
Greater decision-making role 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