International movement on the

quality of genetic testing

services
International Symposium at Kitasato,
March 2008

Stuart Hogarth, University of Loughborough

The future is now

• InterGenetics launch OncoVue in Europe

Sciona
The future is now

• deCODE launch deCODEme, November 2007

The future is now

• DTC polygenic risk assessment in UK

Genosense
Where’s the harm?

‘THE TEST SHOCKED ME INTO EATING BETTER’

“I was worried about stroke as it runs in my family, but it

seems my genes are okay for that. However, I have a
140-fold increased risk of cancer as I don’t clear
pollutants very well – I could lower this risk by eating
more fruit and vegetables, particularly cruciferous ones
like broccoli and cabbage.”

Victoria Hanlon, 27 year-old account executive

after taking Genetic Health’s ‘Premium’ test
Grazia, 26 March 2007
Where’s the harm?

‘UNSUBSTANTIATED AND OVERBLOWN CLAIMS’

“If Virginia Ironside thinks a genetic test can accurately

predict her risk of cancer, heart disease or Alzheimer's,
she is sadly mistaken. Genetic tests, such as the one
she had, are more or less useless in predicting an
individual's risk of developing these diseases. The
companies that sell these tests are making
unsubstantiated and overblown claims about the
predictive power of these tests.“

Rob Elles, Chair of British Society of Human Genetics, et al

Letter sent toThe Independent, November 2007
 Slow down, you move too fast
“[There has been] a noticeable lack
of consensus within the genetics
community about exactly when a
test for a new marker was
sufficiently validated for it to enter
into clinical service.
Some labs rushed to provide
testing after the first publication,
while others waited until the result
had been replicated in multiple
studies or multiple ethnic groups.”
Emily Winn-Deen, Cepheid
(ex-SACGHS member)
IVD Technology December 2003
The regulatory framework

Possible regulatory levers

• Regulations governing medical devices

• Regulations governing clinical laboratories
• General consumer protection legislation
• Controls on advertising
• Clinical practice guidelines
• Codes of practice e.g. ACGT in UK
A policy consensus

Genetic tests should not enter routine

clinical practice without thorough
independent evaluation
ACCE evaluation framework
Analytic validity – accuracy of test identifying the
biomarker
Clinical validity – relationship between the biomarker and
clinical status
Clinical utility – likelihood that test will lead to an
improved outcome
ELSI
Asymmetries of information

• Can we level the playing field?

 Regulatory gaps comparison

Risk Scope of LDTs General

class review approach
USA Moderate Analytic and Only small Proactive
/ high clinical validity subset

Europe Low Only if clinical Yes, but some Reactive

claims? exemptions,
(inc. overseas
suppliers?)
Canada Moderate Analytic and Authority not
clinical validity clear

Australia Moderate Only if clinical Yes

claims?
ACGT code of practice

Code of practice and guidance on human

genetic testing services supplied direct to
the public, September 1997
• Laboratory accreditation
• Confidentiality of data
• Provision of counselling
• Information about test, its scope and limitations, and
the accuracy, significance and use
UK - developments

UK developments

• ACGT Code of Practice

• UK Genetic Testing Network – gene dossiers
• National Screening Committee reviews regulation of
commercial screening services
• Human Genetics Commission – Genes Direct (2003),
More Genes Direct (2007)
Europe - developments
European developments
• Creation of EuroGentest (QA / CRM)
• Revision of IVD Directive (imminent)
• EMEA work on PGx – FDA collaboration (VGDS)
• Council of Europe - Protocol on Genetic Testing
Council of Europe

• Draft additional protocol

• Parties shall take the necessary measures to ensure that
genetic services are of appropriate quality. In particular, they
shall see to it that: genetic tests meet generally accepted criteria
of scientific validity and clinical validity … According to this
provision, it is the responsibility of the State to ensure the
existence of a system (e.g. an approval system), which
guarantees the reliability of a genetic test in respect of a
determined disease, i.e. that its results with regard to the
identification of particular genetic characteristics related to this
disease are accurate and can be reproduced.
Council of Europe

• Draft additional protocol

– For predictive genetic tests … appropriate genetic
counselling shall also be available for the person
concerned. The tests concerned are: - tests predictive of a
monogenic disease; tests serving to detect a predisposition or
genetic susceptibility to a disease; tests serving to identify the
subject as a healthy carrier of a gene responsible for a disease.
– The form and extent of this genetic counselling shall be
defined according to the implications of the results of the
test and their significance for the person or the members of
his or her family, including possible implications concerning
procreation choices.
Global - developments
Australia
• Complete revision of IVD regulations
• Guidance on nutrigenetic tests

Canada
• Guidance on PGx tests

International developments
• OECD QA guidelines for MGT
• GHTF activities – risk classification, conformity
assessment and evaluation of safety/performance
• ICH work on PGx
2006 US developments
July
• FTC/FDA/CDC consumer alert
• GAO report
• Congressional hearing
August
• Sen. Barack Obama issues draft Bill
September
• New FDA IVDMIA guidance
• Draft bill from Sen. Edward Kennedy
2007/8 US developments

• Health Secretary requests oversight study from

SACGHS (Personalised Healthcare initiative)
• IOM convene Roundtable
• Debate about FDA guidance
• Kennedy and Obama bills reintroduced
• SACGHS oversight report to be completed soon
– enhanced role for FDA, greater use of PT etc.

University of Cambridge
Role of IVD device regulations

What they can do

• Premarket review of analytic and clinical validity
• Set clear evidence standards for market entry
• Monitor performance in postmarket environment
• Ensure truth-in-labelling and truth-in-promotion
Role of IVD device regulations

What they can’t do

• Deal with ethical/social issues such as genetic
discrimination
• Regulate clinical practice issues such as informed
consent and confidentiality of personal data
• Evaluate clinical utility - best left to HTA and clinical
practice guidelines
Pre-market review

• Regulation by information disclosure

• Truth-in-labelling (and
truth-in-promotion)

University of Cambridge
Alternatives
Registry concept
• Publicly available register of
• all labs and their tests
• evidence dossiers for all tests?
Alternatives
Registry concept
• Publicly available register of
• all labs
• evidence dossiers for all tests

• Issues
• Who can guarantee quality of information?
• Who deals with complaints?
Postmarket controls

• Education
• Training for health professionals involved in
delivering genetic tests

• Clinical governance
• Increased use of and better funding for
clinical guidelines

• Independent sources of information

• LabTests Online, GeneTests, OrphaNet etc.
Responsive regulation

Three core regulatory functions

• Information gathering
• Standard setting
• Enforcement / compliance
International policy

Forums
• EuroGentest
• Organisation for Economic Cooperation and
Development (OECD)
• World Health Organisation (WHO)
• International Standards Organisation (ISO）
• Global Harmonisation Task Force (GHTF)
International harmonisation

Role

• Information gathering – provide an overview of what

is happening, identify problems and opportunities
• Standard setting – use best practices as a
benchmark for practice, build consensus and thus
help initiate change at nation state level
• Enforcement / compliance – mutual recognition?
International harmonisation

Dangers
• Downward harmonisation

Principles
• Transparency
• Stakeholder inclusion