National Health Committee
Genomics and the
Implications for
Health Care
March 2015
National Health Committee – Genomics and the Implications for Health Care
National Health Committee (NHC)
The National Health Committee (NHC) is an independent statutory body charged with prioritising new
and existing health technologies and making recommendations to the Minister of Health.
It was reformed in 2011 to establish evaluation systems that would provide the New Zealand people
and the health sector with greater value for money invested in health.
The NHC Executive is the secretariat that supports the Committee. The NHC Executive’s primary
objective is to provide the Committee with sufficient information for it to make decisions regarding
prioritisation and reprioritisation of interventions and services. They do this through a range of
evidence-based products chosen according to the nature of the decision required and timeframe within
which decisions need to be made.
The New Zealand Government has asked that all new diagnostic and treatment (non-pharmaceutical)
services, and significant expansions of existing services, are to be referred to the NHC.
In August 2011 the NHC was appointed with new Terms of Reference and a mandate to establish the
capacity to assess new and existing health technologies. Its objectives (under Section 4.2 of its Terms
of Reference – www.nhc.health.govt.nz) include contributing to improved value for money and fiscal
sustainability in the health and disability sector by:
 providing timely advice and recommendations about relative cost-effectiveness based on the best
available evidence;
 providing advice and recommendations which influence the behaviour of decision makers including
clinicians and other health professionals;
 providing advice and recommendations which are reflected in resource allocation at national,
regional and local levels; and
 contributing to tangible reductions in the use of ineffective interventions and improved targeting to
those most likely to benefit.
In order to achieve its objectives under Section 4.2 and to achieve ‘Value for Money’, the NHC has
adopted a framework of four assessment domains – Clinical Safety & Effectiveness; Economic; Societal
& Ethical; and Feasibility of Adoption – in order that assessments cover the range of potential
considerations and that the recommendations made are reasonable.
It is intended that the research questions asked will fall across these domains to ensure that when the
Committee comes to apply its decision-making criteria, it has a balanced range of information available
to it. When the NHC is setting those questions they will have the decision-making criteria in mind.
The 11 decision-making criteria will assist in the determination of the NHC work programme and in the
appraisal and prioritisation of assessments.
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National Health Committee – Genomics and the Implications for Health Care
Contents
1
Introduction
4
2
Clinical application of genomic testing
5
2.1
Genetic risk prediction
5
2.2
Disease diagnosis
6
2.3
Clinical management
6
3
Test performance
8
4
Supporting infrastructure
9
4.1
Diagnostic test assessment
10
4.2
Laboratory perspective
10
4.3
Workforce
11
4.4
Clinical application
12
5
Ethical perspective
13
6
A wider health perspective
14
7
New Zealand services provision
15
8
Summary
16
Glossary
18
References
19
National Health Committee (NHC) and Executive
22
Disclaimer
22
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National Health Committee – Genomics and the Implications for Health Care
1 Introduction
Greater understanding of the human genome offers the opportunity to improve the delivery of
personalised medicine: ‘to tailor medical care to specific individual characteristics, needs and
preferences of a patient, from prevention, to diagnosis, treatment and to follow-up’.(7)
The completion of the Human Genome Project in 2003 was a major driver for the current period of
biomedical discovery, the pace of which continues to accelerate.(1) Genetic predisposition plays a
central role in most common diseases, and is the primary cause of most rare diseases.(8) Enormous
advances have been made in the understanding of genetic disease.(9) The next-generation
sequencing technology will enhance further analysis and the US Food and Drug Administration (FDA)
has recently approved a sequencing technology for use.(10) The cost of genomic analysis is falling and
it may soon be easier and cheaper to sequence the whole genome rather than to extract and test
relevant sections for a number of known mutations.(11)
From the viewpoint of the FDA, personalised medicine has arrived, as since 2011 one-third of new
drug approvals have had an associated genetic or other bio-marker that influences treatment choice.
Patients with breast, colorectal, and lung cancers, and melanomas, can be offered a molecular
diagnosis allowing the selection of treatments that are more likely to improve outcomes.
Genotyping for drug-metabolising enzymes has allowed potential improvements in dosing of drugs.(7)
However, it is recognised that, at the current phase of development, the amount of available data is
increasing significantly, but the capacity for interpretation of the data is still rudimentary, generating
the risk of doing harm.(8) In conjunction it is recognised that access to testing and data will increase
as the cost of testing continues to fall, and the challenges of storage, analysis and interpretation will
be substantial.(9) Additionally, who should be tested, how much of the genome sequenced, what
should be tested, validated and communicated to patients as well sharing data for further
development are key considerations.(12)
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National Health Committee – Genomics and the Implications for Health Care
2 Clinical application of genomic testing
Broadly the areas of health care in which genomic testing is seen to be playing a role, though not
with equal impact, are:
 risk assessment for disease incidence
 disease diagnosis
 clinical management of diagnosed disease for both intervention effectiveness and safety
 surveillance of disease recurrence.
2.1 Genetic risk prediction
The importance of genetics is well recognised in single gene related disorders, where mutation to a
single gene results in the expression of clinical disease. The inheritance of common diseases is
usually polygenic and disease outcome is also dependent on environmental factors.
Genome-wide association studies (GWAS) look for associations between typically thousands of
specific genetic variations, commonly single-nucleotide polymorphisms (SNPs), and particular
diseases or traits. The variations do not cause the disease but are closely linked in space to an
unidentified gene that does influence the disease presentation. Each of the identified variations
tends to have a relatively small individual effect.(4, 6)
Generally the association between individual SNPs and traits is small and currently known variants
explain too little about the risk of disease occurrence to be clinically useful.(3, 13) Testing is possible
for multiple diseases and the predictive results may provide conflicting options: actions may reduce
the risk for one and increase the risk for another disease development.(3) As with other forms of
screening, the potential benefits are dependent on more than test performance alone. The disease
prevalence and the costs and benefits of potential interventions are crucial.(13)
The genetic susceptibility of individuals to developing type 2 diabetes has been elucidated for the
rarer forms of the disease. GWAS of population-based samples have identified loci that influence the
risk of obesity and diabetes, but the effect size of identified variants is small. The overall explained
predisposition is small, up to 10% for diabetes and 1% for obesity. Currently high-risk individuals are
better identified on the basis of known risk factors. There is limited evidence to indicate that
information on genetic disposition can be used to guide modification of long-term behaviour. The
rationale for testing is to improve pathological understanding and to stratify patients for potential
future therapeutic interventions.(4) Similarly, with respect to cardiovascular diseases, there is
insufficient evidence to warrant the use of a genetic risk score based on SNPs.(6)
Direct to consumer testing, a form of screening that provides prediction of risk for future disease, is
available at a cost of about US$100. The clinical usefulness is low.(14)
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National Health Committee – Genomics and the Implications for Health Care
Susceptibility genes increase the risk of an individual developing a particular disease. For example,
mutations of the BRCA1 and BRCA2 genes predispose substantially towards the development of
breast and ovarian cancers, and mutations of the MLH1 and MLH2 genes increase the risk of
colorectal cancer. Testing for these is part of routine practice in specific populations.(15)
2.2 Disease diagnosis
Genomic examination is being used to increase the understanding of the genetic components of
intellectual disability. Copy-number changes, micro-deletions and micro-duplications have been
identified with intellectual disability and autism. About 14% of cases of developmental delay can be
explained by copy-number variation.(5) There is potential to identify biomarkers of Alzheimer’s
disease which could lead to earlier interventions.(16)
2.3 Clinical management
Genomic analysis has become part of clinical practice, particularly in the field of oncology. The
technology has been applied in practice in a number of ways:(15)
 Prognostic indicator. The use of gene-expression markers of tumours to identify prognostic
subgroups and then appropriate therapy options. There is a need to ensure that the testing is
appraised adequately and its use may have implications for the size and complexity of clinical
trials.(15) A health technology assessment, so far unpublished, has considered the benefits and
harms of 11 prognostic tests. The study found that there was good evidence in half that
prognostic accuracy was increased, but evidence was lacking as to whether this led to improved
patient outcomes.1
 Monitoring of disease burden and early recurrence. Monitoring of genetic markers in blood has
been used for haematological cancers and may develop to be effective for solid tumours, in
addition to usual imaging methods.(15)
Pharmacogenomics is the study of the inherited and acquired genetic variation in drug response.(17)
In the cancer field, the following have been used:
 Optimising the use of therapeutics. The expression of particular genes by a tumour can determine
the effectiveness and safety in response to a specific agent, e.g. the metabolism of the
immunosuppressive agent azathioprine is dependent on the presence of the enzyme Thiopurine
S-methyltransferase (TPMT). Its deficiency can lead to serious toxic effects from the drug.(18, 19)
Genomic marker identification has been used to reduce drug adverse reaction in the treatment of
HIV.(20)
 Identification of new therapeutics. The presence of a tumour expressed gene, with an
understanding of how it affects cellular function, may lead to the development of drugs targeted
at that part of the pathway, e.g. the presence of BRAF mutation in melanoma and the
development of drugs that act on specific cellular function to a specific agent.(21, 22)
1
Agency of Healthcare Research and Quality.
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National Health Committee – Genomics and the Implications for Health Care
 Acquired resistance to therapy. Identification of genomic changes in a sub-clone of cancer cells
that indicate resistance to primary therapy may be used to decide on appropriate initial stage
multiple agent therapy.(15)
In cardiovascular medicine it is well known that there is variable patient response to dosing with
warfarin, with impact on the risk of serious adverse events associated with anti-coagulation. Two
common alleles have been identified that have a small fraction of the activity for the enzyme that
metabolises the drug, that results in increased risk of complications. The FDA drug labelling now
includes genetic information. However clinical uptake of the information has been slow.(17) Though
trials show promise, addition of pharmacogenomics has yet to be of proven additional benefit.(23)
The timely access to genomic information to guide prescribing has been a limitation to its potential
use.(10)
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National Health Committee – Genomics and the Implications for Health Care
3 Test performance
In whatever field of health care genomic testing is used, particular tests must provide meaningful
information. The Centre for Disease Control and Prevention has produced the ACCE framework for
evaluating genetic tests (Figure 1). The acronym is taken from its primary components: Analytic
validity, clinical validity, clinical utility and associated ethical, legal and social implications.
Figure 1. ACCE model process for evaluating genetic tests
PPV = positive predictive value; NPV = negative predictive value.
Source: CDC-http://www.cdc.gov/genomics/gtesting/ACCE/
The analytical and clinical validity of the test set the foundations of how well a particular test
operates technically and measures a clinical entity.
The elements of analytical validity include how well it detects the genotype of interest (sensitivity),
how well it classifies samples without the specific mutation (specificity), laboratory quality control
and assay robustness in the face of pre-analytical and analytical variables.
Clinical validity is measured by sensitivity and specificity and the predictive value of the test, which is
dependent on the disease prevalence.
Clinical utility considers the value of testing in the context of real-world clinical delivery.
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National Health Committee – Genomics and the Implications for Health Care
4 Supporting infrastructure
To ensure genetic testing is successfully integrated into medical practice, necessary aspects that have
been recognised include: oversight to ensure the accuracy and reliability of genetic tests; an
educated health care workforce; data protection and protection from discriminatory use.(21) In the
UK, Genomics England is the arm of the Department of Health leading the development of genomic
medicine into the health service. As well as planning to link genomic mapping with 100,000 patients
with selected cancers, infectious diseases and rare diseases, the project plans to develop the
necessary medical scientists and educate the wider medical community to support the technology.
There is also the need to manage and integrate data for clinical and research use.2 A US Centers for
Disease Control and Prevention (CDC) sponsored report, based on engagement with multiple
stakeholders, identifies a number of key elements: professional education, public education,
research to have a public health lens with a health outcomes focus, test assurance and the regulation
of technologies.(24)
A report on the use of whole genome sequencing within the UK health system recommended that
genomic testing should be clinically targeted and with clear benefits over existing tests. Health care
professionals need further development of competencies and support and clear and rational
commissioning pathways are necessary.(11) Given the limitations in understanding genomic data,
testing should be used to answer clinical questions.(12)
Genomic testing will generate large amounts of data that will create a storage challenge.(9) Secure
storage will need to cover retrieval for the individual’s use while allowing approved research access
for the future benefit of all.(25) The development of clinical informatics is crucial.(11) Genomic data
may be incorporated into a national New Zealand breast cancer registry with the amalgamation of
the current regional registries.3
The FDA has considered its position in response to the changing medical technology. It highlights
that in the translation of the biological knowledge there are considerable challenges related to the
accuracy and performance of the diagnostic tests. The co-development of diagnostic tests and linked
therapeutic agents brings an added challenge. In assessing a diagnostic test the analytical validity,
clinical validity and clinical utility are to be assessed. It notes the problems generated when different
testing technologies are used. Diagnostic test kits are standardised and used across laboratories
while laboratory developed tests are site-specific and are more commonly used in the current field of
genomics. This leads to risk in the quality of testing and interpretation.
2
http://www.genomicsengland.co.uk/100k-genome-project/
3
Personal communication: Sector Capability and Implementation, Cancer Services
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National Health Committee – Genomics and the Implications for Health Care
In its response the FDA is developing regulatory standards, reference libraries and research methods.
These include:
 Biomarker Qualification Programme − once a biomarker has been approved within a specified
context of use, drug developers do not need to reconfirm its approval
 MicroArray and Sequencing Control Project − development of standards, quality control and
guidance for these technologies
 Genomic Reference Library for Evaluating Whole Genome Sequencing − sharing of performance
data for instruments and uses
 guidance for clinical trial designs and methodologies.
4.1 Diagnostic test assessment
The CDC has established the Evaluation of Genomic Applications in Practice and Prevention (EGAPP)
to establish and test a systematic, evidence-based process for evaluating genetic tests and other
applications of genomic technology that are in transition from research to clinical and public health
practice. This independent, multidisciplinary panel prioritises and selects tests, reviews
CDC-commissioned evidence reports and other contextual factors, highlights critical knowledge gaps,
and provides guidance on appropriate use of genetic tests in specific clinical scenarios.(26) A summary
of its recommendations are available.4
European Union(27) and UK(28) organisations also assess genetic tests for clinical utility and laboratory
quality management, with the UK Genetic Testing Network leading in the development of
governance that ensures proper evaluation of tests before clinical use.(9)
4.2 Laboratory perspective
The Royal College of Pathologists of Australasia (RCPA) has proposed a National Framework for
Genetic Testing.5 It incorporates assessment of the diagnostic test as well as classification of
laboratories. It is suggested that genetic tests should be classified by clinical utility and that would
determine its availability or not. Tests should be assessed by complexity and classification of
laboratories would determine the range of tests they could offer.
Test by volume and complexity:
 High volume simple testing: technically simple assays, with simple interpretation. For example
BCR/ABL1 testing in chronic myeloid leukaemia.
 Moderate volume complex testing: tests of more complexity than the high volume tests in both
their execution and interpretation. For example Huntington disease testing.
4
http://www.egappreviews.org/recommendations/index.htm
5
RCPA response to Genetics Working Party Chair’s request for options – November 2012
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National Health Committee – Genomics and the Implications for Health Care
 Low volume testing: tests usually more complex in both execution and interpretation, the
complexity compounded by the infrequent nature of the assays, especially if the small number of
assays was distributed over more laboratories than necessary, for example RB1 testing in children
with retinoblastoma.
Classification of laboratory subsequent to test classification:
 Class 1: These laboratories are those approved to perform high volume simple tests only. The
only requirement on a Class 1 laboratory is that it has the New Zealand accreditation to perform
molecular genetic testing.
 Class 2: These laboratories are those approved to perform moderate volume complex testing in
addition to high volume simple tests. These laboratories must operate in close and effective
liaison with relevant specialist clinical services, potentially including genetic and counselling
services.
 Class 3: These laboratories would be classed as national genetic reference laboratories that must
have the requisite clinical and genetic expertise to offer a comprehensive genetic testing and
advisory service for the disorder in question.
4.3 Workforce
Developments in genomic technology are expected to have significant workforce implications. Highly
skilled programmers and analysts are necessary to interpret the complex data. Increased
preventative screening will potentially lead to increased need for multiple professions to be involved
in the interventional response to the screening programme, such as dieticians and pharmacists.(16)
However training, recruitment and retention of laboratory staff is seen as a challenge. There is a
shortage of pathologists as well as technical staff.6
The RCPA recognises the need for workforce development requirements for laboratory staff as well
as clinical referrers.7 Many non-geneticist clinicians have limited insight into the genetics of the
diseases they deal with(29) or of genetics in general.(30)
Education of health professionals could begin with integration of genomics into primary training
programmes in addition to training of existing professionals. Similarly public education can
commence with integration into the school curricula as well as wider community engagement,(24)
including the work of national museums.(31)
6
Community Pathology Services in New Zealand: Environmental Scan and Background Paper, May 2011
prepared for Ministry of Health
7
RCPA response to Genetics Working Party Chair’s request for options – November 2012
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National Health Committee – Genomics and the Implications for Health Care
4.4 Clinical application
The development of simple algorithms will be necessary to help clinician interpretation of genetic
data.(17) Linking results of genomic testing to the patient electronic clinical records may allow
effective use of the information but increases risk of unauthorised access.(21) However, as point-oftesting develops, such as specific testing for drug sensitivity, with rapid results,(8) clinical application
may become easier.
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5 Ethical perspective
In respect of research using medical records and specimen data in conjunction with genomic data,
the consent for future research after the original specimen is collected remains unclear. The
pressure to share data more broadly to enhance understanding brings increased risk to privacy.
Broadening consent is an option to allow further research as knowledge progresses, and overcomes
the issue of retracing participants. However, broader consent for future use of data reduces consent
as there is less clarity at the time of consent. A tiered approach to consent regarding future research
is an option.(21) The UK Genomic project has utilised an “everything can be done” consent for their
data. Participants can be contacted in future to enrol in future trials.(32) Consideration should be
given to consent withdrawal, implications for relatives, what secondary use is allowed and the
potential impact of commercial gain by the private sector from the data.(9) Privacy is at risk through
the linking of databases, even if research data is collected anonymously.(9)
In the US genetic information cannot be used when considering health care insurance, but can be
used by companies when assessing risk of life, disability or long-term care insurance. Employers
cannot use genetic data to discriminate.(21)
As the clinical usefulness of personal genomic screening is considered low, with the risk of
misinterpretation, professional bodies have published position statements and some countries have
regulated its use.(33) It is unknown how individuals may respond to genetic data with an estimation
of future risk. They may react fatalistically and be less inclined to use protective options and so
knowledge of the result does the individual a disservice. Also currently known risk behaviours are
much more important than genetic variation.(9)
When the whole genome is interrogated, in the context of answering a specific clinical problem,
incidental findings can result. These are results that are not directly related to the clinical question.
The interpretation of these results may be less or more clear, and have implications for the individual
or their family. In response to the risk of ‘dumping heaps of molecular uncertainty on patients’,
geneticists in the Netherlands try to interpret exomes provided by clinicians and pass on information
about variants of known relevance plus incidental findings of obvious importance.(8) The American
College of Medical Geneticists issued a policy statement on the reporting of incidental findings.(34) It
provides a list of mutations that should be reported regardless of the indication for testing, based on
their potential to be verified by other means and for the individual to be offered medical
intervention as appropriate. The European Society of Human Genetics recommended filtering of
results to avoid unsolicited results.(35) Proposals for dealing with results from whole genome testing
in Canada considered the issue from ethical guiding principles and with respect to groups of varying
competence and proximity to the person tested. Its recommendations note the need for
professional expertise, use of testing to answer a clinical question, maintenance of confidentiality
and to consider the best interests of the children and adults.(35)
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National Health Committee – Genomics and the Implications for Health Care
6 A wider health perspective
The determinants in health are multifactorial; genetics is one determinant that interacts with
behavioural factors and socioeconomic factors.(36) The FDA, though acknowledging the importance
of genomics in the development of ‘personalised medicine’, also points out that diseases are not only
the result of our genes but that there is an important interaction with environmental, social and
cultural factors.(7) Research using genomics should be done in conjunction with exploring the
environmental contributions to disease.(24) A challenge is to formulate how screening via GWAS
operates without undermining effective population health policies that reduce exposure to the
common risk factors responsible for common diseases.(37)
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National Health Committee – Genomics and the Implications for Health Care
7 New Zealand services provision
The Genetic Health Service New Zealand (GHSNZ) is the provider of expert genetic diagnosis and
advice, and was set up in 2011 to provide a consistent New Zealand wide service. It has 7.8 FTE
consultants and 12.4 FTE genetic counsellors. In 2012/13 the service had nearly 5000 referrals,
arranged 2972 tests at a total cost of $925,000 and an average cost of $310. The expected increase
in demand for services with advances in technology is an acknowledged risk. Currently the GHSNZ
does not have a national database to link family data.(38)
The service expresses concerns about the current clinical utility of some genomic testing, and that
the ability to apply the vast increase in data clinically is a limiting step to its use. A pilot clinical
programme focused on families with undiagnosed rare diseases has been initiated by University of
Otago in conjunction with a genomics corporate. The service recommends that:
 new tests have proven clinical utility and technical and clinical expertise is available
 requesters are fully aware of clinical utility and cost of testing
 GHSNZ does not necessarily have the resources to support referrers, laboratories and DHBs in the
use of tests.(38)
A report commissioned prior to the setting up of GHSNZ noted the current challenges:(30)
 inequity of service delivery
 insufficient IT support
 the need for workforce planning
 the need for demand management
 a lack of genetic knowledge among referrers.
GHSNZ is not involved in ‘companion testing’ where genetic testing determines the clinical value of a
specified medication such as in cancer services. Genetic testing is done in ‘standalone’ laboratories
and can be an income stream for the laboratory. Advice on clinical utility is not requested and
requests come via clinicians who may not have sufficient understanding of the clinical utility of the
test.8
There are New Zealand test result repositories that may be an appropriate starting point to consider
the storage of genomic data.
8
Personal communication, Dr Joanne Dixon, National Clinical Director, GHSNZ, October 2013
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8 Summary
When the previous National Health Committee considered molecular genetic testing in 2003, it
acknowledged future developments following the Human Genome Project, and the challenges it
would bring; the speed of change in knowledge, the level of genetic knowledge among clinicians, the
level of knowledge amongst the public and the configuration of services. Its recommendations
related to assessing tests by their clinical validity and utility, access to safe and effective testing,
quality control and accreditation for laboratory services, workforce development including the
education of the medical providers and more accessible information for the public.(39) These
considerations remain relevant as the potential role for genomic medicine has developed.
A framework to ensure that genomic medicine is provided safely and effectively has a number of
components:
1.
Assessment and designation of specific genomic tests to demonstrate validity and clinical
utility
In order for tests to be provided within the public health system, tests must clear utility based
on evidence. New Zealand does not need to perform this task de novo as US and European
authorities have structures in place currently for this task. New Zealand would be in a position
to transfer the knowledge to its own circumstances. Tests should be applied to the
management of clear clinical questions. The National Laboratory Roundtable strategic
framework identified the opportunity for a national process for the introduction of all new
testing.
2.
Assurance of genomic testing
Assurance of both testing methods and of the laboratories performing tests is required.
Laboratory accreditation could be based on the Royal College of Pathologists of Australasia
tiered approach to laboratory service designation.
3.
Workforce development
The provision of genomic health technology and services requires a skilled scientific workforce
in testing and interpretation environments. The current health care workforce: genetic
specialists, general medical specialists and primary care physicians need to have sufficient
understanding of genomics to be able to apply the technology appropriately to clinical
practice. This requires short to medium-term training as well as longer-term education of the
students. The development and maintenance of the laboratory workforce is already viewed as
challenging.
4.
Public education
The general population needs to be informed and educated in the abilities and limitations of
the technology in order to promote informed decision-making. This too has medium and
longer-term aspects.
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National Health Committee – Genomics and the Implications for Health Care
5.
Information technology development
It is necessary to develop the resources to archive and retrieve the large amounts of data that
are generated in the genome sequencing. Clinically relevant information must be made
available effectively and in a timely manner to clinical IT systems to provide support to
clinicians.
6.
Broader health
The development and application of genomic medicine knowledge to improve health should
be used in conjunction with existing knowledge on the behavioural and social determinants of
health, to provide a coherent approach to achieving health gain.
7.
Ethical
The ethical implications of genomic testing and the possible impact on privacy and
discrimination need consideration within the development of services and more broadly.
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Glossary
Gene
The traditionally defined unit of hereditary.
Genome
The whole of the inheritable information.
Allele
One of two or more versions of a genetic sequence at a
chromosomal location.
Genomics
The study of function and interactions of all the genes in the
genome.
Genetics
Study of single genes.
Exome
Protein coding sequences of the genome.
Polygenic
Produced by two or more genes.
Epigenetic
Non-mutational phenomena that alter the expression of a gene.
Single-nucleotide polymorphism
(SNP)
A single-nucleotide variation in a genetic sequence; a common
form of variation in the human genome.
Mutation
Usually term reserved for genetic variation in DNA that is known
to cause pathology.
Copy number changes
A deletion of duplication of a stretch of DNA.
Germ cells
Gametes that pass on hereditary information to the next
generation.
Germ line changes
Become ubiquitous in the earliest stages of the developing body
and so are present in all cells.
Somatic mutation
A deleterious genetic variation occurring in any cell of the body
except sperm or egg cells. Variations in somatic cells can affect
the person in whom they occur but are not passed on to offspring.
Whole-genome sequencing
Sequencing the coding regions, or exons, of the entire genome.
Next-generation sequencing
DNA sequencing that harnesses advances in miniaturisation
technology to simultaneously sequence multiple areas of the
genome rapidly and at low cost.
Genomewide association study
An approach used in genetics research to look for associations
between many (typically hundreds of thousands) specific genetic
variations (most commonly single-nucleotide polymorphisms) and
particular diseases.
Sources: (1-6)
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References
1.
Feero WG, Guttmacher AE, Collins FS. Genomic Medicine — an Updated Primer. New England
Journal of Medicine. 2010;362(21):2001-11. doi: doi:10.1056/NEJMra0907175.
2.
Guttmacher AE, Collins FS. Genomic Medicine — a Primer. New England Journal of Medicine.
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3.
Manolio TA. Genomewide Association Studies and Assessment of the Risk of Disease. New
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4.
McCarthy MI. Genomics, Type 2 Diabetes, and Obesity. New England Journal of Medicine.
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Paving the Way for Personalized Medicine: FDA’s Role in a New Era of Medical Product
Development2013 27/01/2014. Available from:
http://www.fda.gov/downloads/scienceresearch/specialtopics/personalizedmedicine/ucm372421.
pdf.
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Burn J. Should We Sequence Everyone’s Genome? Yes. BMJ. 2013;346. doi: 10.1136/bmj.f3133.
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Flinter F. Should We Sequence Everyone’s Genome? No. BMJ. 2013;346. doi:
10.1136/bmj.f3132.
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Collins FS, Hamburg MA. First Fda Authorization for Next-Generation Sequencer. N Engl J Med.
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Wright C. Next Step in the Sequence: The Implications of Whole Genome Sequencing for Health in
the U.K2013 September 2013. Available from: http://www.phgfoundation.org/file/10363/.
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Wright CF, Middleton A, Burton H, Cunningham F, Humphries SE, Hurst J, et al. Policy Challenges of
Clinical Genome Sequencing. BMJ. 2013;347:f6845. doi: 10.1136/bmj.f6845.
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National Health Committee (NHC) and Executive
The National Health Committee (NHC) is an independent statutory body which provides advice to the
New Zealand Minister of Health. It was reformed in 2011 to establish evaluation systems that would
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within which decisions need to be made.
Citation: National Health Committee. 2015. Genomics and the Implications for Health Care.
Wellington: National Health Committee.
Published in March 2015 by the National Health Committee
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This document is available on the National Health Committee’s website:
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