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Gabriel Scally

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The degree to which a characteristic is determined by genetics (as opposed to environment) ... Honorary Research Fellows: Dr Thilo Gruning. Dr Sema Mandal. Dr ... – PowerPoint PPT presentation

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Title: Gabriel Scally


1
Welcome
  • Gabriel Scally
  • Regional Director of Public Health
  • NHS South West

2
Genomics and population health
  • David Melzer
  • Epidemiology Public Health

3
outline
  • The promise of sequencing the genome
  • Overview of findings
  • Flood of discovery for common disease and traits
  • Interpreting gene status
  • Implications for PH
  • Biological insights into population distributions
    and the need for population based approaches
  • Regulatory challenge

4
2005 - How the Human Genome Era Will Usher in a
Health Care Revolution -Personalized Medicine
(NHGRI)
  • Prevention
  • Identify those at risk before they developed
    disease
  • Diagnosis
  • Treatment Pharmacogenetics
  • Personalising the drug and dose
  • Avoiding idiosyncratic side effects
  • (gene therapy)
  • Prognosis

5
DNA RNA protein 3 billion base pairs, 20K
genes
Mendel biography, Mawer S, Adams NY 2006
6
Genetic variation between humans
  • gt10 million variants in human genome databases
  • Most common Single Nucleotide Polymorphisms
    (SNPs)

7
Sickle cell mutation changing one amino acid
Public health genetics unit, 2006
8
HeritabilityThe degree to which a characteristic
is determined by genetics (as opposed to
environment).
  • stroke, diabetes, prostate cancer, cardiovascular
    disease, depression and bone degeneration
  • approx 25 - 33 heritability

Sciences et Avernir, 2007
9
GWA studies e.g. UK Wellcome Trust Case Control
Consortium
10
WTCCC study - Type 2 diabetes - Oxford and Exeter
11
FTO AA genotype is associated with a 3kg
increase in adipose tissue
P 3 x 10-35
12
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13
FTO gene status meaning?May 27th, 2008
  • Susannah said
  • I was astonished, and over the moon.
  • and meanwhile my fat friend here to Trinny
    I dont know what youre going to do?!
  • Turning to the fat people who did not have the
    gene, Susannah said
  • "So if we don't have it and we're still fat, it
    must be because we're just greedy pigs who eat
    too many pies!"

14
Obesity epidemic
Mu Boyan 2009
15
LDL cholesterol SNPs in the InCHIANTI study
  • Frequency of respondents by LDL cholesterol
    allele count, with box-plots of the distribution
    of serum LDL cholesterol levels. Dotted lines
    indicate intervention levels of greater than 130
    mg/dl for borderline high levels and greater than
    160mg/dl for high levels.
  • Murray et al European Heart Journal 2009

16
population distributions
Arbitrary risk thresholds inescapable?
17
Flood of SNP discoveries 300
(Melzer, BMJ Feb 08)
18
Age related Macular Degeneration
  • Most common risk of blindness in older people in
    developed countries
  • Population attributable risk 43 for CFH
  • Complement Factor H
  • Plus
  • 20 - smoking
  • 36 for LOC387715

From Mayo Clinic website
Schmidt S, Am. J. Hum. Genet. 200678852864.
19
New biologyFilaggrin mutations, dermatitis and
asthma
  • Nature Genetics 38, 399 - 400 (2006) Skin barrier
    function and allergic risk
  • Thomas J Hudson  Figure 1. Skin barrier function
    and allergic risk.An intact epithelial barrier
    (a) prevents allergens from reaching antigen
    presenting cells (APCs) in subepithelial tissues.
    Damage to this barrier (b) allows allergens to
    penetrate into the subepidermal layer and
    interact with APCs, leading to allergic
    sensitization and, secondarily, to allergic
    manifestations in the host.

20
Regulatory issues Very little clinical
evaluation required of genetic tests (esp. for
labs)
Forbes - 12 Gene Tests That Could Change Your
LifeTCF7L2 DeCode Genetics sells a test for
500 via online test provider DNA Direct.
21
TCF7H2 and Diabetes 2 reduced beta cell
(insulin) function
  • Identified a hot area on 10q1, for diabetes 2,
    within transcription factor 7like 2 gene
    (TCF7L2 formerly TCF4) p value 2.1x10-9
  • replicated in Danish cohort (P 4.8x103) US
    cohort (P3.3x109).
  • Compared with non-carriers
  • OR CC1.00
  • CT1.45
  • TT 2.41
  • Population attributable risk of 21.

From Grant S et al, Nature Genetics 2006
22
Forbes - 12 Gene Tests That Could Change Your
LifeTCF7L2 DeCode Genetics sells a test for
500 via online test provider DNA Direct.
with diabetes or Impaired Fasting Glucose by
TCF7L2 genotype aged 65 in InCHIANTI n944
ADA criteria for Impaired fasting glucose
Melzer, 2006
23
Evidence requirement for clinical tests
Hogarth S, et al . Food Drug Law J.
200762(4)831-48.
24
Policy issues in genetic tests
  • Can balanced regulation be crafted?
  • economically viable, allowing innovation etc
  • Who is responsible for clinical validity (or
    utility)?
  • How much clinical evidence should be required?
  • How accessible should this data be (for
    systematic review etc)
  • A post marketing surveillance system needed?
  • off label use
  • Special measures for ethnic groups?

25
Defying genotype
  • Incidence of Diabetes According to Treatment
    Group and Genotype at Variant rs7903146 (TCF7L2)
  • Diabetes prevention programme n3548 (Florez et
    al, N Engl J Med. 2006 July 20 355(3) 241250.)

26
Conclusions
  • Genes and environment are inseparable
  • That is how evolution works!
  • Explosion of polygenic gene discovery
  • Some great hits but also large number of small
    effect markers
  • Provide a genetic explanation for
  • trait distributions
  • human, system, disease heterogeneity
  • lack of natural boundaries
  • (genetic) Test regulation for clinical validity
    in Europe is non-existent
  • CE mark on a test is worthless!

27
Tobacco control research at the University of
BathProfits and policy how understanding corpor
ations can inform public health policy
Dr Anna Gilmore University of Bath LSHTM
28
Tobacco control research group at Bath
  • Core staff
  • Linda Bauld
  • Anna Gilmore
  • Ken Judge
  • Gordon Taylor
  • Admin/Comms
  • Cathy French (UKCTCS Comms Network manager)
  • Cathy Flower (Admin)
  • Research
  • Dr Gary Fooks (NIH)
  • Dr Katherine Smith (SFP/CRUK)
  • Dr Michelle Sims (DH/HF)
  • Rosemary Hiscock (UKCTCS)
  • John Chesterman (statistician, GCPH)
  • Janet Ferguson (DH/GCPH)
  • Eileen Sutton (SF SW)
  • TBA
  • PhD Students
  • Lucy Hackshaw (PhD CRUK)

29
Focus
30
International grants (AG)
CIHR 18 country (135,000 people) study of
factors influencing tobacco use
Bloomberg tobacco policy in Russia
FP7 11 country study of health well being in
FSU
31
UK Focused Grants (joint)
32
UK Focused Grants (AG)
Systematic review of snus (HF)
Tax price policies in Europe (FP7)
Evaluation of smokefree in ethnic minorities
(IPCT)
33
DH grant
  • Evaluating SF legislation using secondary data
  • SHS exposure
  • Health impacts eg MI
  • Smoking prevalence
  • Working with SW PHO
  • So far examined trends in determinants of SHS
    exposure in children
  • Local relevance need to encourage parents to
    make homes smokefree
  • Evidence base on how to encourage SF homes is
    lacking in UK

34
Geo Mean Cotinine, in children aged 4-15yr,
1996-2007, HSE data
35
UK Focused Grants (LB)
DH PORTS trial (proactive telephone cessation
intervention)
NICE systematic reviews
Cessation service evaluation (2 current projects)
GCPH Feasibility study of incentives for
cessation in pregnancy
36
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37
Aim
  • To establish the UKCTCS as a major national and
    international resource and driver of new
    research, policy and practice approaches to
    reducing the prevalence of smoking and related
    morbidity and mortality through prevention of
    incident smoking, promotion of smoking cessation,
    and the development of more effective harm
    reduction strategies for those currently unable
    to stop smoking.

38
People and Universities
  • John Britton, Ann McNeill, Tim Coleman, Sarah
    Lewis and others
  • Linda Bauld, Anna Gilmore and colleagues
  • Paul Aveyard and colleagues
  • Amanda Amos and colleagues
  • Peter Hajek and colleagues
  • Gerard Hastings and the CTCR
  • Robert West and the HBU

39
  • Profits and policy
  • how understanding 
  • corporations can inform public health policy

40
Corporations as a determinant of health
  • In high income countries the major causes of
    mortality and morbidity have an industry directly
    pushing the product responsible (eg tobacco,
    alcohol, food industries)
  • Corporations also affect health less directly eg
    through the environment built environment
  • Corporations should be recognised as a social
    determinant of health (William Wiist AJPH 2006)

41
Understand corporations
  • Yet not yet a key part of PH practice.
  • Most advanced in tobacco control.
  • WHY? (1) Tobacco industry documents released
    through litigations in US (whistleblowers)

42
2. Because work on the vector pushed by WHO
  • WHO Committee of Experts 2000
  • Tobacco use is unlike other threats to global
    health. Infectious diseases do not employ
    multinational public relations firms. There are
    no front groups to promote the spread of cholera.
    Mosquitoes have no lobbyists.

WHO Committee of Experts 2009
43
WHO (contd)
  • WHA resolution 54.18 (2001)
  • 1.URGES WHO Member States to be aware of
    affiliations between tobacco industry and members
    of their delegations,
  • 2. to be alert to efforts by the tobacco
    industry to continue its subversive practice ..
  • Article 5.3 of the Framework Convention on
    Tobacco control
  • In setting and implementing their public
    health policies with respect to tobacco control,
    Parties shall act to protect these policies from
    commercial and other vested interests of the
    tobacco industry..

Yet simultaneously urging partnership with
private sector, PPPs at forefront of efforts to
address other global health issues
44
Evidence that understanding the industry can
inform/influence policy?
  • availability of the tobacco industry documents
    has spawned an entire new area of investigation
    and has had a substantial impact on .. tobacco
    policy-making. (Givel M, Glantz S. AJPH 2004)
  • Our limited successes
  • Germany Change in way research funded (Gruning,
    Gilmore AJPH)
  • Russia significantly changed opinions of key
    politicians (eg head of the Consumer Protection
    Agency recently attempted legal action against
    BAT), legislation currently being drafted
    informed specifically by document work (Gilmore,
    McKee various papers)
  • Article 5.3 of Framework Convention on Tobacco
    Control Our work secured change in EU position
    ensured strong guidelines (Smith, Fooks, Collin,
    Gilmore. PLOS Medicine)

45
How does understanding the industry help inform
policy
  • Tell you
  • How they lobby influence policy
  • Where the industry are going/what next dangers
    are
  • What works in tobacco control SCREAM TEST
  • How the industry will respond
  • Also
  • Evidence against the industry (support
    legislation litigation)
  • Delegitimise the industry reduces their
    influence

46
Example 1 Impact assessment
  • Work funded by SFP/CRUK
  • Smith KE, Fooks G, Collin J, Weishaar H, Mandal
    S, Gilmore A. "Working the system" How British
    American Tobacco secured changes to the European
    Union Treaty and fundamentally reshaped
    policymaking'. PLOS Medicine (under review)
  • Smith KE, Fooks G, Gilmore A et al . Is the
    increasing policy use of Impact Assessment in
    Europe likely to support or undermine efforts to
    achieve healthy public policy? JECH (submitted)

47
IA in the EU
  • Plays a key role in policy development all
    major policy developments must have IA
  • Seen as providing a transparent and unbiased
    assessment of impacts
  • The form of IA used is claimed to provide
    comprehensive (integrated) assessment of
    impacts, yet critiqued for emphasis on business
    impacts and failure to assess health impacts
  • HOW WHY?

48
BAT secured changes to the EU Treaty (Treaty of
Amsterdam, 1997)
BAT Shaping the Regulatory Environment
Advertising and Public Smoking. Unknown date
http//bat.library.ucsf.edu//tid/xnz82a99
Accessed on 23 May 2008.
49
The multifaceted lobbying approach
50
Why?
  • From late 1980s BAT recognised that risk
    assessment and a form of IA (BIA) could be
    manipulated to further industry interests
  • Specifically, provided a means to prevent the
    introduction of tobacco control policies
    (smokefree legislation advertising controls)

51
Why?
3. More generally, felt IA could influence policy
in favour of industry
(IMPACT). Impact Assessments Changing the Way
Business Deals with Government. 95/06/07
http//legacy.library.ucsf.edu/tid/fjf14a99
Accessed on 24 Jul 2008.
52
Follow up
  • Led to publication of various guidelines on IA
    standards for consultation of interested parties
    by the Commission
  • The IA guidelines have been used to challenge PH
    legislation
  • The standards for consultation have been used to
    justify consultation with the tobacco industry
    to lobby against Article 5.3 of FCTC
  • Preliminary evidence that also influenced system
    of IA in the UK have been working to influence
    interpretation of risk (move away from the
    Precautionary Principle)
  • (FPH Conference)

53
Example 2 UK strategy Future of the industry
  • Ongoing work
  • Some based on company annual reports,
    presentations to investors/investment analysts,
    analyst reports, TI journals, media coverage
  • NB These are available for all corporations
    therefore much research can be done without the
    documents

54
How does understanding the industry help inform
policy?
  • Tell you
  • How they lobby influence policy
  • Where the industry are going/what next dangers
    are
  • What works in tobacco control SCREAM TEST
  • How the industry will respond
  • Also
  • Evidence against the industry (support
    legislation litigation)
  • Delegitimise the industry reduces their
    influence

55
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56
Innovation (Everywhere Annual reports, ppts to
analysts etc)
  • Pan Kwan Yuk, Financial Times, 9 May 2009
    (www.ft.com)
  • Eileen Khoo, an analyst at Morgan Stanley,
    believes the focus on product innovation will
    take on greater importance in the years ahead ..
    "if you want smokers to continue smoking premium
    brands, you have to give them a reason to stay
    loyal to the brand," she says. "And one of the
    best ways of doing that is through slicker
    packaging and new product features such as
    resealable packs, super-slims and charcoal
    filters."
  • Euromonitor International, 2009 Innovation has
    three purposes to justify a premium price, to
    promise a different experience and to suggest a
    reduced risk experience

 
57
How does understanding the industry help inform
policy?
  • Tell you
  • How they lobby influence policy
  • Where the industry are going/what next dangers
    are
  • What works in tobacco control SCREAM TEST
  • How the industry will respond
  • Also
  • Evidence against the industry (support
    legislation litigation)
  • Delegitimise the industry reduces their
    influence

58
How will the industry respond to PP?
  • Legal challenges
  • Trade arguments challenges (including arguments
    that government are expropriating IP claims of
    compensation)
  • Challenge the scientific evidence
  • Produce their own evidence
  • Economic arguments smuggling counterfeiting
    will increase, revenue will fall
  • Use RIA/BIA to show not cost effective
  • Argue that not a TC measure but anti-industry
    measure

59
  • Corporations have a major health impact
  • Understanding corporations can play a key part in
    developing effective public health policy (eg by
    reducing industry influence, ensuring effective
    policy, providing evidence for policy)
  • Imagine if we had an Article 5.3 for every area
    of PH policy!

60
Thank you
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