Experiences of Children Enrolled in Pediatric Oncology ...

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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

Transcript of Experiences of Children Enrolled in Pediatric Oncology ...

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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

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DISCLOSURES None

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"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.

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BACKGROUND

Research is a cornerstone of modern medicine

Research agenda is the sine qua non of pediatric cancer

Cancer clinical research trials Children >>>>> Adults

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BACKGROUND

Pediatric clinical trials are complex

Therapeutic misconception

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WHY IS ASSENT AN IMPORTANT TOPIC? Birth of assent

History of assent National Commission + Belmont

Report American Academy of Pediatrics

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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.

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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.

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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”

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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.

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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

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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” *

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ASSENT IN 2007

ASSENT IN 2009

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BACKGROUND Components of valid assent

Determine children’s understanding Preferences for involvement

Children & the therapeutic misconception

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METHODS

Sample 7-18 year olds with cancer who have

assented to therapeutic clinical trials

Survey instrument (QuAs) Closed-ended Open-ended

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METHODS Eligibility criteria

Sixty-two children

Documented malignancy

Age 7-18 years

Assented to a COG / PBTC research protocol

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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)

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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

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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

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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

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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

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IMPLICATIONS

Clinical trials Gold standard in pediatric heme/onc

Improve understanding

Greater decision-making role When appropriate

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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

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LET ASSENT OUT ITS CAGE