A Public Health Approach to Genomics Throughout the Lifespan
Health Forum of West MichiganGrand Valley State University
December 6, 2019
PAT R I C I A M C K A N E , DV M , M P H
S TAT E M AT E R N A L A N D C H I L D H EA LT H E P I D E M I O LO G I S T
D I R E C TO R L I F EC O U R S E E P I D E M I O LO G Y & G E N O M I C S D I V I S I O N
Over 5 decades of remarkable scientific advances in genetic testing, diagnosis and treatment
https://cysticfibrosisnewstoday.com/2014/09/18/25th-anniversary-cystic-fibrosis-gene-discovery-breakthrough-commemorated/
https://unlockinglifescode.org/timeline
What is public health genomics?
Genomics and family history play a role in many diseases such as cancer and heart disease.
▪ Risk assessment & early identification
▪ Public health education
▪ Stakeholder engagement
▪ Public policy
▪ Prevention, management & interventions for high-risk populations
“A multidisciplinary field concerned with the effective and responsible translation of genome-based knowledge and technologies to improve population health”
~Bellagio Statement, 2006
http://www.nature.com/gim/journal/v8/n7/full/gim200678a.htmlThe path from genome-based research to population health: Development of an international public health genomics networkWylie Burke, Muin J Khoury, Alison Stewart and Ronald L Zimmern for the Bellagio Group
1999Governor’s Commission on Genetic Privacy and Progress
“…recognizes that remarkable advances in basic knowledge in genetics as well as in genetic technology are occurring at a rapid rate…”
Examined issues related to:▪ Privacy of genetic information
▪ Ownership of DNA or genetic samples
▪ Collection, use and storage of DNA
▪ Genetic discrimination
▪ Education
▪ Research
▪ Informed consent for genetic testing
▪ Telemedicine and access
Final report issued 1999
2000Michigan Genetic Privacy Laws
▪ Prevent employers from failing or refusing to hire, recruit, or promote an individual because of a disability or genetic information
▪ Prohibit employers from requiring genetic testing and related information as a condition of employment
▪ Prevent hospital, medical, or surgical policies from requiring applicants to undergo genetic testing
▪ Require physicians to obtain written, informed consent before ordering predictive or pre-symptomatic genetic tests
State Genetics Plan, 2003-2008Vision: Improved health outcomes and an enhanced quality of life for the people of
Michigan through appropriate use of genetic information, technology and services
Goal 1: Increase genetic literacy in the State of Michigan
Goal 2: Assess the public health impact of heritable conditions and utilization of genetic services
Goal 3: Improve access to genetic information, prevention strategies and services
Goal 4: Promote early identification and treatment of individuals with birth defects, heritable disorders or genetic susceptibilities, throughout the life cycle
Goal 5: Identify best practices and promote a policy framework to assure high quality services, supports, and genetic privacy protections
Goal 6: Promote appropriate public health responses to advances in genomic medicine and technology
The Genomics and Genetic Disorders Section provides assessment, policy development, and assurance related to newborn screening, birth defects, genetic disorders, and the use of genomics in public health programs.
Learn more at www.Michigan.gov/genomics
2019
Public Health Genomics in Michigan:A Lifespan Approach
SpecialtyCare
Providers
Hospitals
Primary Care
Providers
Genetics Clinics
Medicaid
WIC
School
Health
Immunization/
Infectious Disease
Genomics & Genetic Disorders
Office of Drug
Control Policy
CSHCS
MCH• Adolescent Health• Family Planning• EHDI • FASD• FIMR • MIHP• Early On
Developmental
Disabilities
Council
Mental HealthServices to Children
Michigan
Care
Improvement
Registry
Local PublicHealth
Health Plans
Epidemiology• BRFSS
• Asthma
• Environmental
Partnerships and Collaborations
Midwest GeneticsNetwork
Chronic DiseaseArthritis • Cancer • Diabetes
• Cardiovascular Disease
Osteoporosis •Tobacco
Laboratory
Vital Records•Birth Defects Registry
•Cancer Registry
A Universal Screening Program
▪ All babies are screened at 24-36 hours of age for rare but serious disorders
▪ Required by Michigan Law (Act 14 of 1987) to make sure that babies who need treatment are found early
▪ Blood spot specimen drawn by birthing hospital or homebirth attendant and sent by courier to state laboratory for screening
▪ Point of care screening tests for hearing loss and critical congenital heart disease are conducted by the hospital or homebirth attendant
From 1 to 50+Michigan’s Newborn Screening Program began in 1965 as a result of Dr. Guthrie’s screening technology to detect PKU.
2019: MI NBS panel includes 57 disorders, including CCHD and hearing screening
0
10
20
30
40
50
60
Nu
mb
er
of
Dis
ord
ers
Number of Disorders in Michigan's Newborn Screening Panel, by Year
New
Existing
Overview of the ACHDNCThe Advisory Committee on Heritable Disorders in Newborns and Children (Committee) was established under the Public Health Service Act, Title XI, § 1109 (42 U.S.C. 300b-10), as amended by the Newborn Screening Saves Lives Reauthorization Act of 2014 (P.L. 113-240).
The mission of the Advisory Committee on Heritable Disorders in Newborns and Children is to reduce morbidity and mortality in newborns and children who have, or are at risk for, heritable disorders.
The Committee recommends that every newborn screening programinclude a Uniform Screening Panel that includes 32 core disorders and 26 secondary disorders.
The Committee advises the Secretary, U.S. Department of Health and Human Services on the most appropriate application of universal newborn screening tests, technologies, policies, guidelines, and standards.
Michigan historically has followed the recommendations of the Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC)
State of Michigan Public Health Code mandated formation of Newborn Screening Quality Assurance Advisory Committee (NBS QAAC) in 2006
◦ “The [NBS QAAC] shall also include in the report recommendations to revise the list to include additional newborn screening tests that are nationally recognized in the scientific literature or national standards for conditions that can be ameliorated or treated if identified by a newborn screening test…”
How Michigan adds conditions
Michigan Newborn Screening Program is occasionally approached by families, state legislators, or clinicians to consider adding other disorders not included on the ACHDNC Recommended Uniform Screening Panel (RUSP)
Needed a systematic approach to review requests
Why implement a tool?
How does Michigan use the tool?
Utilize committee structure ◦ Subcommittee reviews, discusses,
formulates recommendation and presents to TAC
◦ TAC recommends approval to QAAC
◦ QAAC makes final recommendation
◦ Legislature process follows
Readiness TableTotal for each section determines status of condition
Conditions meeting ready or developmental stages can go through Michigan’s approval process
Required criteria include▪ Support from NBS lab, follow-up and Michigan
clinical specialists
▪ Condition is identifiable in newborn period
▪ Sensitive, specific, screening test with high-throughput capability
▪ Established benefits of early intervention and treatment
▪ Condition does not have a known late-onset form (additional caveats must be met if late-onset forms are known)
Criteria sub-sections
Required criteria
Supporting factors◦ Condition characteristics
◦ Laboratory/Screening
◦ Follow-up/Diagnosis
◦ Clinic/Treatment availability
June 2017 – MetQIC met to review GAMT deficiency with condition readiness tool
ACHDNC did not move GAMT to full evidence review due to no prospectively identified cases through NBS system
First use of tool: Guanidinoacetatemethyltransferase deficiency (GAMT)
• Detailed notes from MetQIC discussion
• Caveats and comments from discussion listed in meeting minutes
• Developmental result
Unanimous yes vote by all voting members in attendance to forward
their findings to TAC
Blood Spot Screening
• Cystic fibrosis
• Endocrine disorders
o Congenital hypothyroidism
o Congenital adrenal hyperplasia
• Hemoglobinopathies
o Sickle cell disease
o Other
• Immunodeficiencies
o SCID
o Other primary immune diseases
• Lysosomal storage disorders
o Pompe disease
o Mucopolysaccharidosis, type I
▪ More than 55 disorders
▪ ~300 babies diagnosed each year
▪ Disorders may affect blood cells, brain development, how the body breaks down nutrients from food, lungs, hormones, immune system
• Metabolic disorders
o Amino acid disorders
o Fatty acid oxidation disorders
o Organic acid disorders
o Other- galactosemia, biotinidasedeficiency
• X-linked adrenoleukodystrophy
Michigan Newborn Screening
System
NBS Follow- up: Sickle Cell Disease (SCD)▪ SCD is the most common inherited blood disorder in the US.▪ Most individuals living with SCD in the US are people of color.▪ Included on all state NBS panels, as is Thalassemia.▪ To date over 1,970 newborns have been diagnosed with SCD, with an average of 61 new cases per
year.▪ Most children with SCD are enrolled in Medicaid.▪ Key collaborations with Michigan’s SCD clinics:
• Detroit Medical Center (Karmanos Cancer Institute) Adult SCD clinic.• Children’s Hospital of Michigan-the oldest SCD clinic in MI• University of Michigan Health System- pediatric• Hurley Medical Center -pediatric and adults
▪Representatives from these clinics serve on the Hemoglobinopathy Quality Improvement Committee
State Sickle Cell Disease (SCD) Plan
Goals and Recommendations address:
1. Education and Awareness
2. Transition
3. Provider Shortage
4. Psychosocial/Mental Health Support
5. Medication Adherence
6. Day Treatment Clinics
7. Research
https://www.michigan.gov/documents/mdhhs/MDHHS_Final_SCD_Strategic_Plan_504325_7.pdf
Capacity Building for Sickle Cell Disease Surveillance CDC Cooperative Agreement
Partner with the CDC and 8 states to build capacity for implementing statewide, population-based sickle cell disease surveillance. Outcomes include:
▪Identification of both pediatric and adult patients with SCD and standardize collection of information about their clinical history
▪Increase understanding of the utility of SCD surveillance data among patients, family members, health care providers, and policy makers
▪Increase standardization of methods for SCD surveillance
▪Address gaps in surveillance in pediatric and non-pediatric populations.
▪Goal: Conduct in-depth analyses to inform SCD efforts.
▪ BioTrust program established in 2009 to develop policies and procedures for retention and use of residual NBS blood spots• Assessed public support through surveys and focus groups• Conduct outreach to increase community awareness• Use in a manner acceptable to the public
▪ Advisory boards provide guidance and oversight of operations and review of scientific studies• Community Values Advisory Board• Scientific Advisory Board
▪ MDHHS Institutional Review Board assures protection of human subjects; privacy and confidentiality
▪ Identifiers removed before blood spots are stored with a numerical code at Michigan Neonatal Biobank to optimize storage conditions
A Resource for Population-based Medical and Public Health Research
“The commissioners believe that the newborn screening specimens represent a vital resource for the study and treatment of disease”...
• Public Health Code amended in 2000 to allow use of residual blood spots for medical research
Research using Michigan Blood Spots▪ ~64 approved studies (2009- 2019)
• New NBS assays and quality improvement• DNA methylation, SNP analysis, sequencing candidate genes• Searching for etiologies of cancer, birth defects, chronic disease• Environmental studies• Multi-generational
▪ Example: Genetic Overlap Between Anomalies and Cancer in Kids (GOBACK)• One of strongest risk factors for childhood cancer is being born
with a birth defect• Study hopes to identify novel cancer predisposition syndromes
by determining associations between birth defects and childhood cancer
• Requires large population-based cohort with enough children with birth defects to estimate cancer risk
• Eligible families identified and recruited by MDHHS; Consent to participate obtained by researcher
Whole genome/exome sequencing requires study specific consent.
www.michigan.gov/biotrust
▪ First state to implement informed parental consent for research use of residual NBS specimens, beginning in 2010• Consent form and educational materials
• Training for hospital and homebirth providers on consent process
▪ Consent form included in NBS card, collected by hospital/homebirth provider• 2018 (whole year): 64% consented; 23% declined; 13%
incomplete/not returned
• 69,627 specimens added to the Biotrust research pool in 2018
▪ Parents or individuals (at age 18) can request destruction or opt out of research use.
BioTrust Parental Consent Process
Public Health Implications
Over time the percentage of specimens available for research has increased.
Compared to the screened population, the research pool contains a smaller percentage of non-white newborns, newborns born out of the hospital setting, newborns born to mothers with less years of education and newborns admitted to the NICU, which affects the ability to perform population-based public health research.
Sudden Cardiac Death of the Young (SCDY)▪ ~300 individuals die in Michigan each year (ages 1-39)
• Mortality rates vary by age and race
• Highest rates occur among adults between 30-39 years and among Black males
▪ Sudden cardiac deaths in young people are uncommon but tragic• Often high-profile; especially tragic event for entire community
• Associated with young athletes
▪ 6.3% of Michigan residents reported a family history of SCDY*
• 30% reported an affected first degree relative while ~26% had multiple affected family members
• More Blacks (11.2%) than Whites (5.4%) reported a family history of SCDY
www.wesleonardheartteam.org/
* 2007 Michigan Behavioral Risk Factor Survey
➢ Early detection of individuals at risk, treatment of those with predisposing conditions, & intervention for victim experiencing sudden cardiac arrest
SCDY Prevention
▪ Based on expert mortality review, 21 action steps identified to prevent SCDY
▪ 5 major themes:• Pre-participation sports physicals and screenings• Provider education and public awareness of SCDY risk
factors• Emergency response protocols• Public awareness of cardiac symptoms and CPR/AED
training• Medical examiner protocols
Michigan Alliance for Prevention of Sudden Cardiac Death of the Young (MAP-SCDY)
▪ A statewide collaborative network formed in 2012 that provides leadership, education, and resources to help communities prevent sudden cardiac death of the young
▪ Members include: • Advocacy and support groups• American Heart Association• Athletic trainers• EMS personnel• Medical personnel
• Cardiology• Primary care• Emergency• Genetics• Sports medicine
• Michigan High School Athletic Association• State agencies (Education, Health and Human Services)• School representatives• Vendors (AED)
Dec 2010
MHSAA
Approves
Updated
Form
2003
SCDY Kent
County Study
Completed
First SCDY
Planning
Meeting
May 2004
Feb 2005
Cardiovascular
Health Advisory
Meeting
Key
Informant
Interviews
June 2005
Sept 2005
SCDY
Symposium
Mortality
data
analysis
begins
Sept 2005
Jan 2007
BRFS
Population
Survey
Oct 2007
First
Expert
Review
Meeting
SCDY
Review
Protocol
June 2007
Oct 2008
Pre-
participation
Sports
Screening
Workgroup
convenes
Call to Action Meeting &
“Too Young to Die” Report
Sept 2008
April 2010
Michigan
Student
Athlete
Cardiac
Awareness
Month
SCDY website, video
& expert lectures
created
Oct 2010
Analysis of
Mortality
Records
June 2006MAP-SCDY
2012
2013
MI HEARTSafe
School
Program
2018
MI HEARTSafe
School
Educational
Event
Surveillance Report
update
2018
MI HEARTSafe School Program
http://www.theoaklandpress.com/general-news/20171013/rochester-community-schools-granted-mi-heartsafe-school-designation
• Recognizes schools that meet required criteria to prepare for a cardiac emergency
• 569 schools since 2013• 3 known saves in schools that
were preparing for MI HEARTSafe
Hereditary Cancer
▪ Breast and Ovarian Cancer1
• About 5-10% of breast and 10-15% of ovarian cancers are hereditary
• ~1 in 500 women has a change in the BRCA1 or BRCA2 gene that increases the risk of cancer
▪ Colorectal Cancer
• About 1 in 30 colorectal cancer cases are due to Lynch syndrome2
• Individuals with Lynch syndrome also have increased risk of other cancers
• About 1 in 7,000 to 1 in 22,000 individuals has a gene mutation for familial adenomatous polyposis3
▪ Individuals with a family history of cancer may have a higher risk
▪ Early identification of carriers is important, because some cancers are preventable
1. https://www.cdc.gov/features/lynchsyndrome/index.html 2.https://www.cdc.gov/cancer/breast/young_women/bringyourbrave/hereditary_breast_cancer/index.htm
3. https://ghr.nlm.nih.gov/condition/familial-adenomatous-polyposis#definition
Program Activities
Current focus is on the two most common causes of hereditary cancer: Hereditary Breast and Ovarian Cancer (HBOC) and Lynch syndrome.
We work with clinical and public health partners to:▪ Increase awareness of hereditary cancers▪ Increase cancer family history screening and the use of genetic counseling and testing▪ Improve referral patterns for cancer genetic services▪ Monitor cancer genomics practices in the state▪ Promote national and state policies and guidelines▪ Provide education and training about cancer genomics to Michigan residents, health care
professionals and policymakers▪ Facilitate the Michigan Cancer Genetics Alliance, a collaborative network
Michigan has been awarded funding through cooperative agreements with the Centers for Disease Control and Prevention (CDC) since 2003.
Cancer Genomics Best Practices:1. Documentation of personal and family history to
enable risk assessment.
2. Use of risk assessment tools and genetic services
referral.
3. Appropriate genetic counseling and testing.
4. Appropriate interpretation and discussion of results
with patients.
MDHHS Cancer Genomics Outcomes, 2019-2022Long-term outcomes
• Increase appropriate utilization of genetic counseling and genetic testing.
• Increase proportion of individuals at high risk for hereditary cancer who are counseled and utilize risk management strategies.
Short- and intermediate- term outcomes:• Improve data on hereditary cancer burden and utilization of
cancer genetic services. [Surveillance]• Increase proportion of individuals report that they are aware of
their family history of cancer and report having discussed their associated cancer risk with a provider. [Public Education & Awareness]
• Increase number of providers using family history screening and tumor testing to identify individuals at high risk for hereditary cancers. [Provider Education]
• Improve referral patterns for cancer genetic services. [Policy and Systems Change through Partnerships]
Includes both hereditary breast and ovarian cancer and Lynch syndrome
Numerous resources, activities and collaborative partnerships to address cancer genomics public awareness, surveillance, provider education, and research
