Memorandum by the ESRC Genomics Policy
and Research Forum
The ESRC Genomics Policy and Research Forum
is part of the ESRC Genomics Network (EGN), a major investment
by the Economic and Social Research Council (ESRC) dedicated to
examining the development and use of the science and technologies
of genomics. Established in August 2004, the Forum acts to integrate
the diverse strands of social science research within and beyond
the EGN; to develop links between social scientists and scientists
working across the entire range of genomic science and technology;
and to connect research in this area to policy makers, business,
the media and civil society in the UK and abroad.
The Forum welcomes this opportunity to address
evidence to the House of Lords Science and Technology Committee,
Sub-committee on Genomic Medicine. Social science research on
genomics illuminates a number of questions posed by the Sub-committee
on Genomic Medicine, as follows:
1. USE OF
1.1 What impact will genomic information have
on the classification of disease? How will it affect disease aetiology
and diagnostic labels?
1.1.1 Genetic information has had a significant
impact on the diagnostic classification of a number of single-gene
disorders. Even in single-gene diseases such as cystic fibrosis,
however, genetic techniques have generally been assimilated in
dialogue with existing clinical methods of diagnosis and treatment,
resulting in modification rather than straightforward replacement
of established disease categories (Kerr 2000; Hedgecoe 2003; Latimer
et al 2006). Simple reductionist models of "geneticization"
consequently do not hold. Rather, the incorporation of genetic
and genomic information and techniques into clinical practice,
and the reformulation in practice of disease categories, depend
as much on how that information comes to be used in the clinic
as on basic scientific ideas of aetiology.
1.1.2 The impact of genomic information
is even harder to predict when dealing with the much larger and
epidemiologically more important class of common complex diseases.
It is in relation to such diseases that new genomic techniques
are likely to be most fruitful in identifying genes that confer
an increased risk of disease. In most such cases, however, susceptibility
genes confer only a relatively small increase in the risk of developing
symptomatic disease, while a wide range of environmental, social
and lifestyle factors may contribute to the development of disease
in the presence or absence of any genetic predisposition. Consequently,
the impact of such information on the clinical classification
and diagnosis of disease will depend upon a wide range of variables,
including the size of the genetic contribution to risk and the
availability of effective preventive or therapeutic interventions.
The context of use, and the meaning and utility of genetic and
genomic information in that context, will be a key factor in determining
how such information will be incorporated into clinical practice
and health care delivery.
1.2 How useful will genomic information be
as part of individualised medical advice? What provisions are
there for ensuring that the individual will be able to understand
and manage genomic information, uncertainty and risk?
1.2.1 Utility for patients must be the starting
point for considering how genomic information should be incorporated
into medical advice and health care delivery. From the patient's
point of view, genomic information may be read in a number of
ways. In some cases, knowledge of a genetic predisposition may
relieve feelings of guilt or responsibility for an illness. In
other cases, however, identification of a genetic risk may entail
an additional burden of responsibility on the patient. Indeed,
the language in which medical and policy discussions are couched
commonly tends to suppose that patients have a duty to take appropriate
preventive or prophylactic action. But such action is not always
in the patient's best interest: patients identified with BRCA1/2,
for instance, often feel compelled to undergo prophylactic surgery
out of a sense of duty towards dependent children or out of consideration
for the presumed wishes of their familysubmitting themselves
to operations which they would not have chosen solely on their
own account (Hallowell 1999, 2006). Health care professionals
and others also commonly use identification of a genetic susceptibility
as an opportunity to offer advice on other forms of prevention
including changes in behaviour or lifestyle. However, there is
evidence that patients are less inclined to follow such advice
than to seek specific medical interventions (Saukko et al
2006). Increased testing for susceptibility genes may consequently
lead to a corresponding increase in the numbers of "worried
well" demanding medical monitoring and support (Bharadwaj
et al 2006; Lock et al 2007). Any such increase
will obviously have resource implications for the health services.
1.2.2 The language in which preventive advice
is offered may play an important role in the failure to effect
behavioural change among those deemed to be at increased genetic
risk. Patients often have a complex multi-causal understanding
of inherited risk and prevention that draws on knowledge of their
own family history and the health of relatives (Lock et al
2006). While lay ideas of kinship commonly differ significantly
from genetic accounts of relatedness, knowledge of family history
nonetheless provides a useful medium of communication between
health care advisors and patients. In this respect, overly rigorous
insistence on a strictly genetic understanding of relatedness
may inadvertently lead to a failure of communication and foreclose
on a valuable channel for offering meaningful advice on risk and
prevention (Hall et al 2007).
1.3 What are the implications of developments
in genomic technologies for the training of medical specialists
and other health professionals? Are there any gaps that need addressing?
What is the assessment and planning for future needs in capacity?
1.3.1 Until recently, responsibility for
providing genetic health care and advice has largely devolved
onto genetic medicine specialists and genetic counselors. With
increased knowledge of the genetic dimensions of common complex
diseases, however, a much wider spread of practitioners are likely
to find themselves called on to offer advice on genetic matters.
There will therefore be a need not only to increase provision
of specialist training, but also to integrate appropriate training
in providing genetic health care into the core medical curriculum.
1.3.2 In view of the necessity, discussed
above, of engaging with lay understandings of disease inheritance
and causation, such training should not be confined to a scientific
appreciation of disease genetics. It should also emphasise the
value of family history as an effective means of structuring communication
with patients, and should stress the importance of understanding
that history from the patient's perspective as well as from a
strictly genetic point of view.
1.3.3 Awareness of genetic risk necessarily
has implications not just for individuals but also for their relatives.
Patients' decisions about whether or not to disclose information
about genetic risk to other family members are commonly guided
by lay ideas about who counts as a relative, as well as by judgments
about whether relatives will be able to cope with the knowledge
that they are at risk (Clarke et al 2005). Here too, sensitivity
to lay understandings of kinship, and an appreciation of the dynamics
of family life and the judgments that inform disclosure within
the family, will be invaluable to the practitioner. This will
involve far more than an understanding of the kinds of general
ethical principles that are commonly taken to guide disclosure
of medical information, but which often prove difficult to apply
to complex concrete situations, particularly where family relationships
are concerned. Experience suggests that training in such issues
is often more effectively achieved by working through actual cases
than by consideration of abstract principles.
1.4 Use of genomic information in a healthcare
1.4.1 Genetic and genomic information represent
a significant addition to the medical information available to
health care practitioners and their patients. But the meaning
and utility of that information in a healthcare setting is not
determined solely by the possibility of estimating the extent
of the genetic risk that patients face. It also depends upon the
practitioner's ability to relate that risk to the patient's life
and circumstances, including the social and moral complexities
of family life. As more and more genomic information becomes available
in an increasingly wide range of healthcare settings, it is important
that practitioners learn to help their patients make sense of
that information on their own terms and in their own interests.
2.1 What opportunities are there for diagnostics,
therapeutics and prognosticsnow and in the future?
2.1.1 As discussed above, practical returns
on the identification of specific genetic risk in common complex
diseases are diminishing, in view of the relatively low penetrance
of most susceptibility genes, the confounding aspects of environment
and lifestyle, and the resulting difficulties in drawing useful
lessons or identifying useful interventions. It is possible that
improved genomic understanding of disease aetiology may in time
lead to novel forms of therapy, but such gains are likely to be
piecemeal and unpredictable.
2.1.2 Developments in the field of pharmacogenetics,
including the identification of genes for positive or adverse
drug responses, are likely to follow a similar pattern to the
identification of disease susceptibility genes. A number of single-gene
pharmacogenetic effects have already been identified that may
prove useful in practice, and it is likely that further such effects
will be found. However, genetic explanation of remaining variations
in drug response, and the development of effective tests, will
be complicated in practice by factors including low penetrance
and other sources of personal variation. There is thus a likelihood
of significant but relatively localised pharmacogenetic gains
in the efficiency and efficacy of drug use, but a revolutionary
shift towards so-called "personalised medicine" is unlikely.
2.2 How meaningful are genetic tests which
use genome variation data? What progress has been made in the
regulation of such tests?
2.2.1 The question of the meaning of genomics-based
genetic testing in medical practice and in patients' lives has
been considered above. These considerations also have implications
for how the utility of new genetic and genomic techniques should
be evaluated (Wilfond and Thomson 2000). Any assessment of utility
should take account of the complex meanings that attach to genetic
testing, and the ethical and social consequences that follow from
the application of such tests. This would be best achieved by
adopting recent developments in health technology assessment which
pay explicit attention to the context of use, and which draw on
new methods of engaging with usersincluding both practitioners
and patientsto ensure that new technologies meet genuine
needs (Lehoux and Blume 2000; Lehoux et al 2004).
3. POLICY FRAMEWORK
3.1 Does the existing regulatory and advisory
framework provide for optimal development and translation of new
technologies? Are there any regulatory gaps?
3.1.1 Within the limits discussed above,
significant public benefits are likely to accrue from pharmacogenetic
targeting of medicines on those genetic sub-populations that are
most likely to benefit. However, there are a number of ways in
which the existing regulatory and policy environments are less
favourable for such developments than they might be.
3.1.2 First, commercial incentives alone
may prove insufficient to encourage commercial development, validation
and marketing of pharmacogenetic interventions. Pharmaceutical
companies continue to favour "blockbuster" models of
commercialisation, and are generally reluctant to pursue strategies
that potentially segment their markets. Consequently, development
of new genetically targeted drugs has been slow, despite high-profile
exceptions such as Herceptin. Where already-licensed medicines
are concerned, pharmaceutical companies are particularly disinclined
to encourage the development of genetic tests that may lead to
segmentation of existing markets. Development of such tests therefore
tends to fall to small and medium-sized companies, which do not
have the resources to pursue the large-scale clinical trials needed
to demonstrate efficacy and stimulate demand. There is thus a
serious risk of market failure in such areas. Policy measures
to combat these problems might include extension of orphan drugs
legislation to cover "orphan genotypes", and increased
funding from public sources for clinical studies to develop the
evidence base in support of pharmacogenetic testing and prescribing
(Melzer et al 2005; Hedgecoe et al 2006; Martin
et al 2006).
3.1.3 Secondly, while regulatory control
over the licensing and marketing of medicines is chiefly exercised
at EU level, regulation of genetic and other diagnostic tests
remains a national responsibility, with considerable variation
between member states. Also, licensing procedures for diagnostic
tests generally require little information about clinical utility,
so fail to generate the kind of information that would encourage
uptake by clinicians and patients. Harmonisation of regulatory
procedures, stronger requirements to demonstrate utility, and
incorporation of test procedures into the licensing requirements
for pharmacogenetic medicines might all serve to address these
deficiencies (Melzer et al 2005; Hedgecoe et al
2006; Hopkins et al 2006).
3.1.4 Thirdly, while pharmaceutical companies
have been reluctant to adopt pharmacogenetic methods as a means
of targeting prescribing practices, they have incorporated pharmacogenetic
methods into drug development and evaluation processes. To this
end they have collected considerable amounts of genetic data from
trials participants. Regulations governing these biobanks also
vary widely between European states, inhibiting research initiatives
that might cross national boundaries. Harmonisation of the relevant
EU regulations might do much to address this problem (Hedgecoe
et al 2006).
3.2 Policy Framework: Conclusion
3.2.1 The development of pharmacogenetics
is one of several factors conducing to a radical reorganisation
of innovation pathways in the pharmaceutical and diagnostic technology
sectors. To date, pharmaceutical companies have resisted such
changes, but they appear increasingly inevitable. An appropriately
structured regulatory and policy environment, including effective
engagement with relevant stakeholders, will be crucial in managing
such changes to minimise disruption and maximise public benefit
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15 April 2008