Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Expanding Newborn Screening
Expanding Newborn Screening
Duane Alexander, M.D.Duane Alexander, M.D.
Director, Eunice Kennedy Shriver National Institute of Child Health
and Human Development
Director, Eunice Kennedy Shriver National Institute of Child Health
and Human Development
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
DISCLAIMERDISCLAIMER
While the factual information
presented is referenced, any
opinions stated are those of the presenter and not necessarily of
the NIH or the DHHS.
While the factual information
presented is referenced, any
opinions stated are those of the presenter and not necessarily of
the NIH or the DHHS.
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
THE BEGINNING: PKUTHE BEGINNING: PKU
• Description by Foling 1934
• Proposals for dietary treatment by Woolf
and others 1951
• Need for Rx to begin early (Bickel and
Grueter 1960)
• Development and approval of Lofenalac 1958
• Robert Guthrie’s screening test 1960
• Description by Foling 1934
• Proposals for dietary treatment by Woolf
and others 1951
• Need for Rx to begin early (Bickel and
Grueter 1960)
• Development and approval of Lofenalac 1958
• Robert Guthrie’s screening test 1960
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
IMPACT ON MENTAL RETARDATION
IMPACT ON MENTAL RETARDATION
• Status before 1960• Prevention of PKU sparked a fire
– Optimism – could finally do something– Shift of investigators to MR– Shift of research from institutions to
academic centers– Find and treat other PKUs
• Status before 1960• Prevention of PKU sparked a fire
– Optimism – could finally do something– Shift of investigators to MR– Shift of research from institutions to
academic centers– Find and treat other PKUs
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
PRESIDENT KENNEDY’S PROGRAMPRESIDENT KENNEDY’S PROGRAM
• New Institute at NIH (NICHD) to fund MR research• President’s Committee on Mental Retardation• Construction of MRRCs• Establishment of UAFs• Advertising Council Campaign advocating that
the new PKU test “should be a must for all babies everywhere”(All in advance of data on effectiveness)
• New Institute at NIH (NICHD) to fund MR research• President’s Committee on Mental Retardation• Construction of MRRCs• Establishment of UAFs• Advertising Council Campaign advocating that
the new PKU test “should be a must for all babies everywhere”(All in advance of data on effectiveness)
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
CB/NICHD STUDY OF EFFICACYCB/NICHD STUDY OF EFFICACY
• AAP report in 1965 noted lack of data on efficacy, said
“a collaborative study to evaluate management of this disease would be valuable.”
• Also pointed out (without citation) that initially
some infants were harmed by excessive or unnecessary treatment
• 1967– Launched U.S. Collaborative Study of Children
treated for PKU (224 Children)– Diet initiated early led to normal growth, levels of IQ
comparable to sibs without PKU, should be
maintained throughout childhood– Best predictor: age diet begun
• AAP report in 1965 noted lack of data on efficacy, said
“a collaborative study to evaluate management of this disease would be valuable.”
• Also pointed out (without citation) that initially
some infants were harmed by excessive or unnecessary treatment
• 1967– Launched U.S. Collaborative Study of Children
treated for PKU (224 Children)– Diet initiated early led to normal growth, levels of IQ
comparable to sibs without PKU, should be
maintained throughout childhood– Best predictor: age diet begun
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
MANDATING SCREENINGMANDATING SCREENING
Following the lead of Massachusetts, New York, Louisiana, and Rhode Island, many states moved quickly to mandate newborn screening for PKU
• Prevalence: 1 in 14,000 births• Variants: Non-PKU hyperphenylalaninemia• False positives (95% of screen positives)• False negatives (up to 10% missed)• Efforts to improve
Following the lead of Massachusetts, New York, Louisiana, and Rhode Island, many states moved quickly to mandate newborn screening for PKU
• Prevalence: 1 in 14,000 births• Variants: Non-PKU hyperphenylalaninemia• False positives (95% of screen positives)• False negatives (up to 10% missed)• Efforts to improve
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
OTHER PROBLEMSOTHER PROBLEMS
• Dietary management• Level of PA control• How long to continue
• Maternal PKU• NIH Consensus Conference
• Addition of other disorders• National Research Council Report
1975• Skip to today
• Dietary management• Level of PA control• How long to continue
• Maternal PKU• NIH Consensus Conference
• Addition of other disorders• National Research Council Report
1975• Skip to today
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
<10 Disorders (3)
10-19 Disorders (10)
U.S. Newborn Screening
Conditions Required – June 1, 2006
(Conditions available as an option to selected population are not counted)
30-39 Disorders (12)
40-49 Disorders (15)
50+ Disorders (9)
20-29 Disorders (2)
DC
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
LESSONS LEARNEDLESSONS LEARNED
• Proceed with caution to avoid harm, but proceed to take advantage of preventive potential
• If we apply the lessons learned when we broke new ground, we can implement expanded screening responsibly
• Proceed with caution to avoid harm, but proceed to take advantage of preventive potential
• If we apply the lessons learned when we broke new ground, we can implement expanded screening responsibly
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
HOW TO PROCEEDHOW TO PROCEED
• Make programs comparable across states• Improve screening technology emphasizing
DNA-based approaches• Aggressively pursue development and testing
of therapies for disorders currently lacking effective treatment
• Evaluate tests to minimize false positives and negatives
• Make programs comparable across states• Improve screening technology emphasizing
DNA-based approaches• Aggressively pursue development and testing
of therapies for disorders currently lacking effective treatment
• Evaluate tests to minimize false positives and negatives
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
HOW TO PROCEED (CONT’)HOW TO PROCEED (CONT’)
• Have a confirmatory test system in place to operate quickly with clear parental counseling
• For treatable conditions, have a science-based service delivery and follow-up system in place
• Expand screening to include disorders that do not yet have proven preventive therapy available, and provide a registry of such patients (with parental approval) for possible future research participation.
• Have a confirmatory test system in place to operate quickly with clear parental counseling
• For treatable conditions, have a science-based service delivery and follow-up system in place
• Expand screening to include disorders that do not yet have proven preventive therapy available, and provide a registry of such patients (with parental approval) for possible future research participation.
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
MAKE NBS PROGRAMS COMPARABLE ACROSS STATES
MAKE NBS PROGRAMS COMPARABLE ACROSS STATES
• The consequences of program variability• Equity is an ethical imperative• Current variability• Sources of variability
– State legislation– Payment system– Costs of individual tests– Variation in prevalence of conditions by state
• One corrective approach: A single unified test system
• The consequences of program variability• Equity is an ethical imperative• Current variability• Sources of variability
– State legislation– Payment system– Costs of individual tests– Variation in prevalence of conditions by state
• One corrective approach: A single unified test system
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
IMPROVE NBS TECHNOLOGYIMPROVE NBS TECHNOLOGY
• Current system – different test for almost every disorder (same source -- blood spots – but different tests)
• Impact of tandem mass spectroscopy (MS/MS) • Potential DNA-based systems
Screen for anything we have the gene for• Genetic metabolic disorders with MR• Immunodeficiencies• Hemoglobinopathies, Coagulopathies• Muscular dystrophies• Cystic Fibrosis • Hereditary deafness syndromes
• Congenital hypothyroidism separate• NICHD solicitation
• Current system – different test for almost every disorder (same source -- blood spots – but different tests)
• Impact of tandem mass spectroscopy (MS/MS) • Potential DNA-based systems
Screen for anything we have the gene for• Genetic metabolic disorders with MR• Immunodeficiencies• Hemoglobinopathies, Coagulopathies• Muscular dystrophies• Cystic Fibrosis • Hereditary deafness syndromes
• Congenital hypothyroidism separate• NICHD solicitation
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
DEVELOP NEW THERAPIES FOR DISORDERS WITHOUT EFFECTIVE TREATMENT
DEVELOP NEW THERAPIES FOR DISORDERS WITHOUT EFFECTIVE TREATMENT
• Part of justification for screening for these
disorders• Screening makes patients with rare disorders
available for study of new treatments pre-symptomatically
• NICHD Solicitation• Registry• Consent
• Part of justification for screening for these
disorders• Screening makes patients with rare disorders
available for study of new treatments pre-symptomatically
• NICHD Solicitation• Registry• Consent
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
EVALUATE TESTS TO MINIMIZE FALSE POSITIVES AND NEGATIVES
EVALUATE TESTS TO MINIMIZE FALSE POSITIVES AND NEGATIVES
• Balance in drawing cut-off lines• Lab variability• Concerns of costs and parental anxiety • SACHDGDNC evaluating each new test before
recommending addition• Ongoing monitoring and standardization
– Regional Collaboratives/National Coordinating Center
• DNA-based system could help
• Balance in drawing cut-off lines• Lab variability• Concerns of costs and parental anxiety • SACHDGDNC evaluating each new test before
recommending addition• Ongoing monitoring and standardization
– Regional Collaboratives/National Coordinating Center
• DNA-based system could help
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
CONFIRMATORY TEST SYSTEM WITH PARENTAL COUNSELING
CONFIRMATORY TEST SYSTEM WITH PARENTAL COUNSELING
• Essential due to false positives/negatives in screening
• Included in SACHDGDNC criteria for adding new tests
• Regional Collaborative/National Coordinating Center
• Rapid, precise results confirmed by experts and conveyed by counselors to family and medical home
• Essential due to false positives/negatives in screening
• Included in SACHDGDNC criteria for adding new tests
• Regional Collaborative/National Coordinating Center
• Rapid, precise results confirmed by experts and conveyed by counselors to family and medical home
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
TREATMENT INITIATION AND FOLLOW-UP MONITORING
TREATMENT INITIATION AND FOLLOW-UP MONITORING
• For treatable conditions and those lacking definitive therapy
• Regional collaboratives provide/refer• Gather follow-up data on effectiveness under
guidance of National Coordinating Center– Each disorder, each treatment
• For treatable conditions and those lacking definitive therapy
• Regional collaboratives provide/refer• Gather follow-up data on effectiveness under
guidance of National Coordinating Center– Each disorder, each treatment
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
EXPAND SCREENING TO INCLUDE DISORDERS WITHOUT DEFINITIVE TREATMENT
EXPAND SCREENING TO INCLUDE DISORDERS WITHOUT DEFINITIVE TREATMENT
• Treating before symptoms develop is only way to intervene early enough in degenerative disorders
• Newborn screening only way to detect those without a previous affected sibling
• Requirements• Consent to screen (parents prefer to
alternative)• Counseling• Supportive treatment
• Treating before symptoms develop is only way to intervene early enough in degenerative disorders
• Newborn screening only way to detect those without a previous affected sibling
• Requirements• Consent to screen (parents prefer to
alternative)• Counseling• Supportive treatment
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
EXPAND SCREENING TO INCLUDE DISORDERS WITHOUT DEFINITIVE TREATMENT
EXPAND SCREENING TO INCLUDE DISORDERS WITHOUT DEFINITIVE TREATMENT
• Registry (maintained by RC/NCC or CDC)• Parental consent• Confidential• List by disease• Agree to be contacted when new therapy
study is available• Outcomes of studies maintained by
registry
• Registry (maintained by RC/NCC or CDC)• Parental consent• Confidential• List by disease• Agree to be contacted when new therapy
study is available• Outcomes of studies maintained by
registry
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
THE LEGISLATIVE AND ETHICAL IMPERATIVE
THE LEGISLATIVE AND ETHICAL IMPERATIVE
• No one’s DNA information should be used to discriminate against them in employment or insurance
• Unless we assure by national legislation that such discrimination will not happen, parents will be reluctant to have their newborns screened in a public program
• No one’s DNA information should be used to discriminate against them in employment or insurance
• Unless we assure by national legislation that such discrimination will not happen, parents will be reluctant to have their newborns screened in a public program
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
THE LEGISLATIVE AND ETHICAL IMPERATIVE (CONT’)
THE LEGISLATIVE AND ETHICAL IMPERATIVE (CONT’)
• Proceeding with caution includes providing this protection as well as all the medical and laboratory procedures identified
• If we conscientiously apply what we have learned, provide the necessary funding support and continue to learn, newborn screening will take its full place among the most significant and effective public health measures of all time
• Proceeding with caution includes providing this protection as well as all the medical and laboratory procedures identified
• If we conscientiously apply what we have learned, provide the necessary funding support and continue to learn, newborn screening will take its full place among the most significant and effective public health measures of all time