Genetics, Research and the Public Health The Case for Public Health Genetics Dr Ron Zimmern MA, FRCP

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Genetics, Research and the Public HealthThe Case
for Public Health GeneticsDr Ron Zimmern MA,
FRCP, FFPHMDirector, Public Health Genetics
Unit, Cambridge

• NHS R D Forum, Keele University
• 12 July 2004

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Structure of Talk

• Public health genetics
• Concepts in public health genetics
• Competencies and the knowledge base
• The research agenda in public health genetics
• Policy considerations

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Definitions

• Public Health
• The art and science of promoting health and
  preventing disease through the organised efforts
  of society
• Public Health Genetics
• The application of advances in genetics and
  molecular biology on promoting health and
  preventing disease

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Framework for the Integration of Genetic Science
into Health Services
KnowledgeBase
Genetic Testing HTA and HSR Regulation and QA
Analysis Assessment
Epidemiology Policy Analysis
Building Infrastructure for the Decades Ahead
Practice
Research
Clinical, laboratory and public health practice
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Analysis and Assessment

• 1. Human genome epidemiology
• The systematic application of epidemiological
  methods and approaches in population based
  studies of the impact of human genetic variation
  on health and disease
• prevalence of genotype
• measures of effect relative risk, absolute
  risk, population attributable fraction
• gene-gene and gene-environment interaction
• Policy analysis
• science, commercial, information, educational,
  financial
• public involvement
• ELSI implications

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Action and Policy Development

• Development of health service capacity to
  integrate genomics into health care and building
  infrastructure
• manpower planning
• education and training
• research and development
• partnerships and interdisciplinarity
• working with the commercial sector

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Evaluation and Assurance
I. Health Technology Assessment
The ACCE Framework for genetic test evaluation

• Two specific technical problems
• Distinction between diagnostic tests, and
  predictive and susceptibility tests
• Clinical validity and the population context

• A nalytical validity
• C linical validity
• C linical utility
• E thical, legal and social

• Health Services Research
• Effectiveness and cost-effectiveness of service
  delivery

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Regulatory Issues

• Three Levels
• Statutory
• legislation
• regulation
• codes of practice
• Resource Allocation
• NICE and HTA
• commissioners
• Clinical
• governance
• education

• Issues in Regulation
• Regulation of laboratories and regulation of
  tests
• Regulation of products and regulation of service
• Genetic tests
• How are they to be defined?
• Are they special and should they be regulated in
  a different manner?
• Simple tests and complex tests?
• 4. Regulation of over the counter tests and
  regulation of professionally ordered tests
• 5. In house tests and tests placed on the
  market
• 6. Adquacy of existing regulations
• The EU Directive
• Consumer legislation and regulation

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Concepts in Public Health Genetics
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Genetics

• 1. Genetics as inheritence
• single gene disorders inherited in a mendelian
  fashion
• genetic services
• familial association
• 2. Genetics as cell and molecular biology
• the genetic component of all human traits and
  diseases
• the basis of development
• modern biology

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Determinants of Health
Genetic
Genetic Endowment
Biological
Physical
Natural Environment
Political
Social
Structural Environment
Behavioural
Individual Behaviour
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Gene-Environment Interrelationship
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Population and High Risk Approaches
Shift of population distribution
Geoffrey Rose Complementary approaches
90 100 110 120
130 140 150 160 170 180
Systolic B/P
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Inherited and Complex Diseases

• Inherited diseases
• Cystic fibrosis Duchenne muscular dystrophy
• Huntingtons disease Familial polyposis coli
• Familial hypercholesterolaemia Phenylketonuria
• Complex diseases
• Diabetes Cardiovascular
• Cancer Alzheimers
• Hypertension Schizophrenia
• Rheumatoid arthritis Learning disability

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Penetrance
Gene (Genotype)
Other Genes
Environment
Genetic Risk
Gene-gene interaction
Gene-environment interaction
Disease Risk
Disease (Phenotype)
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Development of Disease
0 10 20 30 40 50 60 70 80 90
Environmental Factors
Latent Period
Induction Period
Genetic Component
Death
Clinical Onset
Idea from Khoury and Cohen (1988) J Clin Epid 41,
1181
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Gene-environment Interaction
Heart disease
PKU
Schizophrenia
Cancer
Motor vehicle accident
Cystic fibrosis
Multiple sclerosis
Alzheimers
Diabetes
Fragile X
Asthma
TB
Duchenne muscular dystrophy
Struck by lightning
Obesity
Rheumatoid arthritis
Meningococcus
Autism
Totally Genetic
Totally Environmental
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Risk, Genes, and Environment
Environmental Exposure TOTAL RR 2.0
Prev95 RR1.05
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Complexity in Genetic Science

• Gene-gene interaction
• Control of transcription
• Alternative splicing
• Post translational modification
• Temporal effects

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Genetic Exceptionalism

• Genetic exceptionalism is the claim that genetic
  information is sufficiently different from other
  types of health information that it deserves
  special protection or other exceptional measures

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Genetic Exceptionalism
Arguments For
Arguments against

• 1. Concern about genetic prophecy - can predict
  our medical future
• 2. Concern for kin- relevant to other family
  members
• 3. Concern for discrimination -
  stigmatisation
• 4. Concern for identification- unique nature
  and stability of DNA

Adapted from TH Murray Genetic Exceptionalism
and Future Diaries (1997)
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The Impact of Genetics
A better understanding of disease mechanisms
A new categorisation of disease based on genotype
Greater diagnostic potential through genetic
testing
A faster and more rational drug discovery process
Novel therapeutic interventions and
pharmaco- genetics
Opportunities for the prediction and prevention
of disease
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Susceptibility Testing and Prevention

• 1. Genotype-phenotyope correlation
• 2. Public acceptability
• 3. Effective interventions
• 4. Behaviour and compliance
• Societal implications - justice and
  discrimination

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Competencies and the Knowledge Base
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Genetic Literacy and Society

• Specialists in public health genetics
• Health professionals and health service managers
• Media
• Commercial, legal and financial community
• Policy makers
• Politicians
• Patients
• General public

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Professonal Competence
THE SCIENCE
PROFESSIONAL COMPETENCE IN PUBLIC HEALTH GENETICS
Interpersonal Skills
Personal Development
THE ART
Political Sensitivity Ethnicity Cultural
differences
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Knowledge Base for Public Health Genetics

• GENETIC SCIENCE
• Basic concepts of mendelian genetics
• Family histories and pedigrees
• Risk assessment and communication
• Principles of genetic epidemiology
• Principles of molecular genetics
• Genetic testing and screening
• Genetics of common disorders
• Gene-environment interaction

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Proposals for Public Health Genetics in UK

• Establish a sub-specialty of public health
  genetics
• Establish competencies and training programme
• Establish 12 posts in the UK over next 5 to 6
  years
• 9 in England 1 in Wales 1 in Scotland and 1 in
  N. Ireland
• Establish links with NHS R D agenda and
  specialised commissioning
• Establish an understanding of the commercial
  sector and its relevance for public health

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Education in Genetics for Health Professionals

• Strategy for increasing the knowledge and
  understanding of genetics across the health care
  professions
• physicians, nurses, pharmacists, dieticians,
  public health professionals, health service
  managers
• Commitment of Wellcome Trust to background report
• Strategy commissioned jointly by Wellcome Trust
  and DH
• Wide involvement of professional and public
  stakeholders

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Addressing Genetics, Delivering Health

• Main Findings
• Importance of genetics accepted but most
  practitioners are still at the stage of
  unconscious incompetence
• Genetics is worthy of a special initiative
• Developing genetics education will be a huge
  undertaking, unprecedented in its scale and
  complexity
• Main Recommendations
• There should be a National Steering Group to
  ensure strategic leadership and commitment
• There should be an Education Centre to provide
  focus, coordination and energy to the work
• A major programme should be established to raise
  awareness, develop genetics in formal and
  informal curriculum and educate by support to
  clinical practice
• Substantial resources will be required
  2-3million pa simply to provide a supporting
  infrastructure

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The Research Agenda in Public Health Genetics
Epidemiology, Health Technology Assessment,
Health Services Research Ethical, Legal and
Social Research
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Epidemiological Research

• DNA banks
• population based
• disease based
• Primary research
• linkage studies
• genetic association studies
• gene-environment interaction
• Secondary research
• systematic reviews
• meta-analysis

A stored collection of genetic samples, in the
form of blood or tissue, that can be linked with
medical and geanological or lifestyle information
from a specific population, gathered using a
process of generalised consent. Austin et al
(2003) UK BioBank, DeCode (Iceland), Estonia,
Latvia, CartaGene (Canada)
Methodology for appraising association studies
Meta-analysis of lipoprotein lipase and heart
disease Meta-analysis of CYP2D9 and
Warfarin Estimates of family history risk in
common conditions
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?32 heterozygotes partly protected from infection
and show slower disease progression to AIDS
Chasman DI et al. (2004) JAMA 291, 2821-2827
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Metabolic Gene Variants and Cigarette Smoking
Smokers showed the greatest reduction in birth
weight (av.1285g) Non-smokers with same
genotype showed no decrease in birth weight
Adverse effects of smoking modified by maternal
genotype
Wang X et al. (2002). JAMA. 287, 195-202
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van de Vijver MJ (2002). N Engl J Med. 347,
1999-2009
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Research Activities in the PHGU (1)

• Health Technology Assessment
• Use of molecular genetic testing in FH
• Evaluating the ACCE methodology for genetic tests
• Gene expression arrays and cancer
• 2. Health Service Research
• Pathways of care in the genetic testing of
  childhood learning disability
• Establishment of a database for health economic
  studies in genetic services
• Nutrigenomics

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Research Activities in the PHGU (2)

• 3. ELSI Research
• IPR and DNA patents
• Regulatory bodies for genetic technologies
• Legal aspects of stem cell research
• Governance of medical databases
• Genetic research in ICUs capacity and consent
• The law and human tissue
• Causation in epidemiological research
• Conceptual analysis of disease with special
  reference to genetics
• Regulation, information and genetics

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• Policy Considerations

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A Framework The Nuffield Genetics Scenario
Project
Two drivers 1. Science and its capacity to
improve human health 2. Public attitudes towards
genetics
External Drivers
Public attitudes
Science
Political and policy machine
The regulatory framework

• Six policy issues
• 1. The regulatory framework
• 2. Educational strategies
• 3. The science base
• 4. Commercial considerations
• 5. Information and confidentiality
• 6. Financial framework for health

Educational strategies
Commercial
Info and confidentiality
Financial Framework
Heatlth Services
Ethical, legal social
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Science and Its Capacity to Improve Human Health
Science and its capacity to improve human health
Pace at which genetic science will impact on
health and health services uncertain

• Is the science too complex? Will it be too
  expensive?
• Can it deliver?
• economic constraints
• scientific constraints

Pace - optimists and realists
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Public Attitudes Towards Genetics

• Widespread misunderstanding about genetics
• genetic determinism
• genetic risk

Public attitudes towards genetics
Role of media and of scientists Legacy of
eugenics Public disquiet about genetic
discrimination
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YES
OPTIMUM SITUATION
PUBLIC ACCEPT
NO
-
YES
SCIENCE DELIVERS
NO
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YES
Basic science progresses No proven clinical
benefit
Public eager and accept but science cannot deliver
PUBLIC ACCEPTS
NO
YES
NO
SCIENCE DELIVERS
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YES
Stage II Public acceptance declines due to
failure of science to provide benefits
PUBLIC ACCEPTS
NO
YES
SCIENCE DELIVERS
NO
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YES
PUBLIC ACCEPTS
Science delivers but public do not accept
Luddite views Stop advances in knowledge
NO
YES
SCIENCE DELIVERS
NO
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YES
PUBLIC ACCEPTS
Stage II Continued demonization of science
destroys science base
NO
NO
SCIENCE DELIVERS
YES
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Conclusion

• Genetic factors are important determinants of
  health and disease in human populations
• Genes are not (in most instances) deterministic
  of disease, interacting as they do with each
  other and with environmental factors
• Genetic exceptionalism should be resisted
• Genetic science and its impact on health is ill
  understood and steps should be taken to improve
  genetic literacy among health professionals and
  across society as a whole
• Genetic factors should be taken into account in
  epidemiological studies
• Those involved in HSR and HTA should develop an
  understanding of genetic science in view of its
  growing impact on health service provision
• Public health genetics should be developed as an
  essential element of the public health workforce
• The impact of genetics on society will depend as
  much on public acceptance as on scientific
  developments
• The application of genetics to benefit human
  health will be determined as much by geenral
  policy considerations (science, commerce,
  regulation) as to specific changes in service
  provision within the NHS

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