Treuman Katz Center for Pediatric Bioethics Conference A Tale of Two Cities Genomics and parental decision-making Genomics and parental decision-making Benjamin 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

Treuman Katz Center for Pediatric Bioethics Conference A Tale of Two Cities How should advances in testing capabilities shift the analysis of the ethical issues in pediatric genetic testing? Clinical integration of new genomic tests How should these tests be regulated? Genetic testing in children What role should parents play?

Treuman Katz Center for Pediatric Bioethics Conference

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? 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?

Treuman Katz Center for Pediatric Bioethics Conference 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 screeningAdult onset conditions

Treuman Katz Center for Pediatric Bioethics Conference 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 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

Treuman Katz Center for Pediatric Bioethics Conference Newborn 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

Treuman Katz Center for Pediatric Bioethics Conference Unifying rationales for these different approaches Timely clinical benefitRight to an “open future”

Treuman Katz Center for Pediatric Bioethics Conference 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 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

Treuman Katz Center for Pediatric Bioethics Conference The 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

Treuman Katz Center for Pediatric Bioethics Conference 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

Treuman Katz Center for Pediatric Bioethics Conference 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 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

Treuman Katz Center for Pediatric Bioethics Conference 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

Treuman Katz Center for Pediatric Bioethics Conference 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.” “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/ACMGAJHG, 57: , 1995

Treuman Katz Center for Pediatric Bioethics Conference 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 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

Treuman Katz Center for Pediatric Bioethics Conference

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

Treuman Katz Center for Pediatric Bioethics Conference 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 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

Treuman Katz Center for Pediatric Bioethics Conference 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

Treuman Katz Center for Pediatric Bioethics Conference 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

Treuman Katz Center for Pediatric Bioethics Conference Meaningful information Clinically important Personally importantly Clinically interesting Personally interesting

Treuman Katz Center for Pediatric Bioethics Conference 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

Treuman Katz Center for Pediatric Bioethics Conference Need for further research Parental interest Understanding Impact on child rearing and child development Parental interest Understanding Impact on child rearing and child development

Treuman Katz Center for Pediatric Bioethics Conference 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

Treuman Katz Center for Pediatric Bioethics Conference 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? 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?

Treuman Katz Center for Pediatric Bioethics Conference “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

Treuman Katz Center for Pediatric Bioethics Conference 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