Treuman Katz Center for Pediatric Bioethics - 2008 Conference A Tale of Two Cities Genomics and...

Treuman Katz Center for Pediatric Bioethics - 2008 Conference

A Tale of Two CitiesA Tale of Two CitiesGenomics and parental

decision-makingGenomics and parental

decision-making

Benjamin S. Wilfond MDBenjamin S. Wilfond MD

Director, Treuman Katz Center for Pediatric Bioethics Seattle Children’s Hospital

Professor and Chief, Division of Bioethics. Department of Pediatrics University of Washington School of Medicine

Director, Treuman Katz Center for Pediatric Bioethics Seattle Children’s Hospital

Professor and Chief, Division of Bioethics. Department of Pediatrics University of Washington School of Medicine


A Tale of Two CitiesA Tale of Two Cities

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

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

Clinical integration of new genomic testsHow should these tests be regulated?

Genetic testing in childrenWhat role should parents play?


Genomic testingGenomic 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?

• 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?


Parental decision making for genetic testing

Parental decision making for genetic testing

• Limited by professionals’ concerns about what is in children’s 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?

• Limited by professionals’ concerns about what is in children’s 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?

Newborn screening Adult onset conditions


Testing for adult onset disorders and carrier testing for recessive disordersTesting 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

• 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


Newborn screeningNewborn screening

• Most common application of pediatric genetic testing

• Often done without parental awareness

• Occasionally performed over parental objections

• Most common application of pediatric genetic testing

• Often done without parental awareness

• Occasionally performed over parental objections


Unifying rationales for these different approaches

Unifying rationales for these different approaches

Timely clinical benefit Right to an “open future”


Timely clinical benefitTimely 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

• 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


The right to an open futureThe right to an open future

• Parents should not be able to make decisions that seriously limit a child’s 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

• Parents should not be able to make decisions that seriously limit a child’s 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


Limiting parental discretion only for

serious risks of harm 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

• 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


Empirical data about risksEmpirical 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

• 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


Pragmatically, current approaches acknowledge some parental discretion

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

• 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


An uncertain policyAn 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.”

• “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, 57:1233-41, 1995


Impact of data on practice and policyImpact 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

• 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


The changing paradigm of clinical genomics

The changing paradigm of clinical genomics

Genetic testingOne test

= One gene

One (or few) interpretations

Genomic testingOne test

= Many (or all) genes

Limitless interpretations


Genomic testingGenomic 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

• 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


Should parents be able to scan their child’s genome?

Should parents be able to scan their child’s 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 don’t know what children will do with this information

• 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 don’t know what children will do with this information


Some parental interest in genomic testing can be anticipated

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

• 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


Meaningful informationMeaningful information

Clinically Clinically importantimportant

Personally Personally importantlyimportantly

Clinically Clinically interestinginteresting

Personally Personally interestinginteresting


The impact of these new technologies on children is not known

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

• 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


Need for further researchNeed for further research

• Parental interest

• Understanding

• Impact on child rearing and child development

• Parental interest

• Understanding

• Impact on child rearing and child development


What will the data show?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

• 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


Advising parentsAdvising 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?

• 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?


“Neither the best of times, nor the worst of times”

“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

• “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


A Tale of Two CitiesA Tale of Two Cities

Mandatory Restricted

Need for education and support about decisions regarding what information to request

and how to interpret the results

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