PEDIATRIC ETHICS AND CHILDHOOD CANCER RESEARCH

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PEDIATRIC ETHICSAND CHILDHOOD CANCER RESEARCH

• Eric Kodish, M.D.
• Rainbow Center for Pediatric Ethics
• Rainbow Babies and Childrens Hospital

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• American Academy of Pediatrics Vision Statement
• We believe in the inherent worth of all
  children. The are our most enduring and
  vulnerable legacy.
• -AAP 1999

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PEDIATRIC ETHICS

• BENEFICENCE
• RESPECT FOR PERSONS
• JUSTICE

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Principles of Medical Ethics

• Respect for Persons is dominant principle for
  adult ethics (autonomy)
• Beneficence is dominant principle for pediatric
  ethics (best interests of child)

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The Geometry of Pediatric Ethics
child
parents
clinician
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Two Questions in Pediatric Ethics

• Should a particular
• therapy be given? BENEFICENCE
• Who should make a
• consent decision? AUTONOMY
• The answers may be incompatible

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Informed Consent vs. Parental Permission

• Autonomous authorization of adults on their own
  behalf is more robust than parental permission
  for children by proxy/surrogate
• the pediatricians responsibilities to his or
  her patient exist independent of parental desires
  or proxy consent. (American Academy of
  Pediatrics 1995 statement on informed consent,
  parental permission, and assent in pediatric
  practice)

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Parental Permission

• Is not the moral equivalent of informed consent.
• Problems surrogate decision necessarily less
  authentic
• Use of best interests vs. substituted judgement
  standard

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PROXY CONSENT

• SUBSTITUTED JUDGMENT
• subjective
• respects autonomy

• BEST INTERESTS
• objective
• promotes beneficence

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Informed Consent in Pediatrics Parental
Permission Assent of Child
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Assent A Clinical Definition

• Awareness of the nature of his/her condition
• What to expect with tests and treatment(s)
• Assessment of understanding (including pressure
  to accept/assent)
• Soliciting an expression of willingness to
  accept the proposed test/treatment

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Assent A Clinical Definition

• Regarding this final point, we note that no one
  should solicit a patient's views without
  intending to weigh them seriously. In situations
  in which the patient will have to receive medical
  care despite his or her objection, the patient
  should be told that fact and should not be
  deceived.
• -AAP COB 95

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Assent A Research Definition

• A childs affirmative agreement to participate
  in research. Mere failure to object should not,
  absent affirmative agreement, be construed as
  assent.
• -CFR 46.402 (b)

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Assent Clinical vs. Research

• Research is supererogatory
• Assent/dissent determinative in research but not
  in clinical context
• Veto power for all 3 moral actors?
• For all studies, the older the child the more
  ethically justifiable (if assent is provided)

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Informed Consent Data

• Direct Observation and audiotaping of consent
  process for children recruited to CCG leukemia
  RCTs, followed by extensive parent interviews and
  clinician reports.
• Findings The RCT is generally explained, but
  many parents do not understand their choice about
  the clinical trial (32), and do not understand
  randomization (52)
• Minorities and those in lower social position are
  at greatest risk for non-understanding, and ask
  fewer questions.
• This data may not be generalizable to the relapse
  context but is a potential concern for Phase II
  Window studies
• (funded by RO1CA83267)

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DECISION MAKING PREFERENCE

• I prefer
• 1. to leave all decisions regarding treatment
  to my childs doctor.
• 2. that my childs doctor makes the final
  decision about which treatment will be used, but
  seriously considers my opinion.
• 3. that my childs doctor and I share
  responsibility for deciding which treatment is
  best.
• 4.to make the final selection of my childs
  treatment after seriously considering my doctors
  opinion.
• 5.to make the final selection about which
  treatment my child will receive.

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DECISION MAKING PREFERENCE

N 108 parents
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Parent Questions by Race and Social Class

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Log of Parent Questions by Race and Social
Position
All cases ANOVA.002
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THE NUREMBERG CODE

• 1. The voluntary consent of the human subject is
  absolutely essential.
• (This means that the person involved should have
  legal capacity to give consent)

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Can we adhere to Nuremberg and do pediatric
research?

• If the answer is no, children as a group will
  suffer.
• If the answer is yes, how can children be
  adequately protected?

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How can we respect Nuremberg and do pediatric
research?

• 1) Parents as surrogates Permission
• 2) Involve Children Assent
• 3) Societal Protection IRB approval

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Approvable Research 4 categories

• 46.405
• 2) Involving greater than minimal risk but
  presenting the prospect of direct benefit to the
  individual subject, if
• risk justified by anticipated benefit to subject
• RB ratio lt alternatives
• parental permission and assent obtained

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RESEARCH ETHICS

• RISK always means to the subject
• BENEFIT may include
• benefits to the subject
• benefits to other patients
• benefits to society (i.e., knowledge)
• benefits to investigator/sponsor

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PEDIATRIC RESEARCH ETHICS
Best interests of child-subject
Science to benefit others
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PHASE I ONCOLOGY RESEARCH IN CHILDREN

• The controversy over therapeutic intent
• Commensurate experience (46.406 creep)
• --should not be a valid justification
• Prospect of direct benefit is the ethical and
  regulatory key
• Problems defining benefit more than a tumor
  measurement
• Considering the alternatives...

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OPTIONSPHASE I ALTERNATIVE HOPSICE
MEDICINE CARE

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OPTIONS(pathways to hope??)PHASE
I ALTERNATIVE HOPSICE MEDICINE CARE

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PHASE I ONCOLOGY RESEARCH IN CHILDREN

• Subject selection is not a controversy
• Qualifies as research with the prospect of
  direct benefit
• Potential for benefit mitigates but does not
  eliminate the need for protection from research
  risk

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ALTERNATIVE MEDICINE

• Vulnerability concerns
• Incredibly prevalent
• Hard to define
• Pediatric differences
• Obligation to prevent harm
• Need to study
• Need to communicate

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HOSPICE

• Not incompatible with Phase I study
• Underdeveloped in children, needs advocacy
  approach
• Reject the idea of a right way to die each
  child and family is unique
• Must be part of the consent process for Phase I
  studies a responsibility to the dying child

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PHASE II WINDOW DESIGN

• Subject selection controversial How poor is
  poor prognosis? Context is everything.
• Qualifies as research with the prospect of
  direct benefit, but may not be as good for the
  subject as alternatives (multi-agent)
• New therapeutic paradigms may change ethical
  acceptability of these studies.

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CONCLUSIONS

• Good ethics starts with good science but good
  science is not inherently ethical.
• It follows that some research with tantalizing
  potential may need to be rejected on ethical
  grounds.
• Accelerated drug development research in
  childhood cancer should proceed, but long-term
  follow up data must be collected and analyzed.

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Children are both vulnerable subjects in need of
protection from research risks and a neglected
class that needs better access to the benefits of
research.