A Tale of Two Cities

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A Tale of Two Cities

• Genomics and parental
• decision-making

Benjamin S. Wilfond MD
Director, Treuman Katz Center for Pediatric
Bioethics Seattle Childrens Hospital
Professor and Chief, Division of Bioethics.
Department of Pediatrics University of Washington
School of Medicine
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A Tale of Two Cities
Clinical integration of new genomic tests How
should these tests be regulated?
Genetic testing in children What role should
parents play?

• How should advances in testing capabilities shift
  the analysis of the ethical issues in pediatric
  genetic testing?

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Genomic testing

• New technologies are commercially available
• Personal Utility, Choice, Recreational Testing
• As problematic as day-spas, a 200 cabernet, or
  pet psychics?
• Even if this is appropriate to offer to the
  public, should parents be able to obtain such
  testing for their children?
• 1. How should the ethical analysis developed for
  pediatric genetic testing be applied to genomic
  testing in children?
• 2. How might genomic testing stress the
  fault-lines of the traditional ethical
  approaches to testing children?

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Parental decision making for genetic testing
Newborn screening
Adult onset conditions

• Limited by professionals concerns about what is
  in childrens interests
• These limitations continue to be criticized for
  not adequately respecting parental
  decision-making
• Will new genomic technologies shift the
  equilibrium towards expanded or reduced parental
  discretion?

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Testing for adult onset disorders and carrier
testing for recessive disorders

• Not routinely offering such testing in children
• ASHG/ACMG 1995
• AAP 2001
• Such testing is done in children as a consequence
  of
• Prenatal Diagnosis
• Newborn Screening

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Newborn screening

• Most common application of pediatric genetic
  testing
• Often done without parental awareness
• Occasionally performed over parental objections

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Unifying rationales for these different
approaches
Timely clinical benefit
Right to an open future
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Timely clinical benefit

• The greater likelihood, proximity and magnitude
  of clinical benefit
• The greater the willingness to recommend,
  persuade or require testing
• As the potential clinical benefit becomes less
  likely, more distant, or less profound
• The greater the willingness to not recommend,
  persuade or prohibit testing

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The right to an open future

• Parents should not be able to make decisions that
  seriously limit a childs future
• Not agreeing to PKU screening
• Could result in preventable mental retardation
• Testing a young child for BRCA or APOE
• Could limit later decisions as an adult to forgo
  testing

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Limiting parental discretion only for serious
risks of harm

• Parental discretion for education, religion, and
  sports
• Treatment for chronic disease
• Focus on communication, trust, and relationships
• Medical interventions for psychosocial benefits
• Apnea monitors, Orthotic helmets, Cleft lip
  repair
• The approaches to both NBS and childhood testing
  are not consistent with respect for parental
  discretion

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Empirical data about risks

• Newborn screening
• Risk of harm from forgone NBS is very low
• Most families readily accept NBS
• Limited provisions for requiring subsequent
  treatment
• Respecting discretion becomes more important new
  tests are introduced with less immediate benefits
• Testing children for adult onset diseases
• Traditional risks have been speculative and
  overstated
• Preexisting impact of living in high risk family
• Reduced anxiety from certainly
• Simply incorporated into identity, like cystic
  fibrosis or diabetes

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Pragmatically, current approaches acknowledge
some parental discretion

• Newborn screening
• Even mandatory program may permit parents to
  opt out
• Greater appreciation of the importance of
  education
• Testing children for adult onset diseases
• Current professional statements acknowledge some
  contexts where testing is appropriate

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An uncertain policy

• Thus, when faced with uncertainty, the provider
  may be obligated to avoid the possibility of
  harm, rather than to provide unclear benefits.
  There may be rebuttable presumption to defer
  testing unless the risk/benefit ratio is
  favorable.
• On the other hand, in specific cases where the
  benefits and harms of genetic testing are more
  uncertain, more weight should be given to the
  wishes of the competent adolescent and the
  parents.

ASHG/ACMG AJHG, 571233-41, 1995
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Impact of data on practice and policy

• Applying current policy approaches to guide
  practice recommendations
• Using standard criteria in current policies
• Timely medical benefit
• Open future
• Current data support increased parental
  discretion using current policies
• Applying data to revise policy approaches
• Current data support revising policies to support
  greater parental discretion when benefit/risks
  are less clear
• Cautioning parents about testing and recommending
  deferral of decisions until child is capable of
  participating in the decision

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The changing paradigm of clinical genomics
Genomic testing One test Many (or all)
genes Limitless interpretations
Genetic testing One test One gene One (or
few) interpretations
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Genomic testing

• Interpretations will be ever changing
• Ongoing epidemiological studies and clinical
  trials will both clarify and contradict our
  understanding of gene-environment-behavioral
  interactions
• Interpretations will need to be selected
• Based on computer algorithms applied to personal
  profiles

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Should parents be able to scan their childs
genome?

• The standard answer on the medical board exam
• No
• Why?
• No clear medical benefit
• Scope will include behavioral traits, which may
  increase social stigma, and remove the choice for
  the later adult
• Even if less harm found for childhood testing in
  high risk families, we certainly dont know what
  children will do with this information

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Some parental interest in genomic testing can be
anticipated

• Genomic testing will be routinely offered in
  children because of valuable clinical uses at
  some point
• Some parents may want additional information
• Information about child health is consistently
  reported as a strong reason parents seek their
  own testing
• As personal utility is given more weight, the
  distinction between health related information
  and recreational information will blurred
• Some parents will want a wider range of
  information about their children

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Meaningful information
Personally interesting
Clinically interesting
Personally importantly
Clinically important
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The impact of these new technologies on children
is not known

• Clinical concerns about testing might increase as
  tests are used to direct clinical decisions
• Clinical management decisions based on
  misinterpreted or misunderstood information can
  result in adverse health outcomes
• But, is this any worse than many evidence-based
  decisions that turn out be harmful?
• Psychosocial concerns about genetic testing might
  decrease when everyone potentially has access to
  all their genomic data
• Incidental findings and returning results
• Sharing information with family members
• Or, there may be greater need to involve families
  to improve interpretations

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Need for further research

• Parental interest
• Understanding
• Impact on child rearing and child development

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What will the data show?

• Limited parental interest
• Impact of marketing?
• Limited understanding
• Impact of education?
• Limited impact on the life of a child
• Difficult to distinguish from social,
  environmental, cultural, geographic, and economic
  influences
• Impact diminishes as genomic tests become routine
  and unending interpretive challenges become
  familiar

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Advising parents

• Parents will need advice and recommendations
  about how to approach genomic information
• Requesting all information and interpretations
  will be a meaningless request
• Reframing the Request
• Which information?
• At what time?
• Why?

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Neither the best of times, nor the worst of
times

• Directive recommendations for parents to obtain
  some data but not other data will be important
• Need to accommodate those parents who want more
  or less than we think is appropriate
• Some parental discretion about which algorithms
  to use on newborns and young children once
  genomic profiling is economically feasible
• Consistent with general trend
• Less novelty and more acceptance over time
  because of the broad range of information, rather
  than discreetly important and not important
  information

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A Tale of Two Cities
Mandatory
Restricted
Need for education and support about decisions
regarding what information to request and how
to interpret the results