APPENDIX 5: VISIT TO WASHINGTON DC,
Members visiting Members visiting: Lord Patel (Chairman),
Lord Colwyn, Baroness Perry of Southwark and Lord Warner. In attendance:
Mrs Elisa Rubio (Clerk) and Professor Tim Aitman (Specialist
The trip was hosted by the National Human Genome
Research Institute (NHGRI), part of the National Institutes of
Health (NIH), and meetings were held at Lawton Chiles International
House on the NIH campus over the three days of our visit.
The NHGRI, one of 27 institutes and centres that
made up the NIH, and was a major contributor to the Human Genome
Project, which had as its primary goal the sequencing of the human
genome. The NHGRI's mission encompassed a broad range of studies
aimed at understanding the structure and function of the human
genome and its role in health and disease and supported studies
on the ethical, legal and social implications of genome research.
It also funded the training of investigators and the dissemination
of genome information to the public and to health professionals.
The NHGRI received its funding through annual Congressional appropriation.
Its 2007 budget was $486 million.
Wednesday 4 June
Session 1: State of Science in Genomics
Presentations by Dr Francis Collins, Director
of the NHGRI; Dr Teri Manolio, Director of the Office of
Population Genomics, NHGRI; Dr Stephen Chanock, Chief, Laboratory
of Translational Genomics; and Dr Jeff Schloss, Programme
Director for Technology Development Coodination, Division of Extramural
Dr Collins summarised developments in genome
science, from the delivery of the double helix structure of DNA
in 1953 to the sequence of the human genome in 2003. Technology
advances, particularly dramatic reductions in sequencing and genotyping
costs, had led to an exhilarating pace of discovery in the past
two to three years about the genetic basis of common diseases
such as multiple sclerosis, rheumatoid arthritis and Crohn's disease.
He described parallel discoveries for genomic testing of drug
efficacy and highlighted new opportunities for disease treatment
that had arisen from this new knowledge, for example new drug
development and gene therapy.
Dr Manolio emphasised that the new genome-wide
association studies (GWAS), in which the Wellcome Trust had played
a key role, had a requirement for very large sample sizes and
for sophisticated IT. Fifty five GWAS had now been published.
There had been few, if any, similar bursts of discovery in biomedical
research previously. The studies had yielded many insights into
the genetic basis of individual common diseases, and had also
revealed a shared genetic basis, previously unsuspected, for a
range of apparently diverse disorders. Dr Manolio also highlighted
the potential for errors in such large studies, and that these
initial studies, whilst very positive, were only skimming the
surface in our understanding of the causes and potential treatments
of common disease.
Dr Chanock talked about the advances in understanding
the genetic basis of cancer since the start of GWAS in 2006. For
example in prostate cancer, the number of known genes had risen
from one to 16. However these tools did not allow measurement
of environmental contributions and it was also not known how these
genetic factors interacted with one another. Therefore the completion
of many GWAS should be seen as just the start in the long road
to understanding the genetic basis of diseases such as cancer.
Dr Schloss described the extraordinary advances
in sequencing technology that had taken place over the past few
years. Alongside a massive increase in sequence output, there
had been a 100-fold reduction in sequencing costs over the last
ten years. Cost reduction by a further 10,000-fold was a current
aim which would permit the sequencing of a human genome for just
$1000. The NIH had so far awarded grants totalling $99 million
to help achieve this goal. Dr Schloss also described many
new technologies that were currently being supported in pursuit
of the more immediate goal of the $100,000 genome, which should
be achieved by late 2008 or early 2009.
The newly discovered genes for common diseases could
lead to advances in diagnostics and therapeutics over the following
five years. Insights into the genetic basis of breast cancer and
colon cancer, for example, were already leading to changes in
screening programmes for these disorders. Within five years, it
would be possible to prove that new interventions were clinically
useful on an individual basis. Therapeutic advances would take
place by using the newly discovered genes as therapeutic targets
but clinical trials of new drugs acting on these targets would
take longer, perhaps 10-15 years.
It was difficult to disaggregate genetic and epigenetic
effects, though epigenetic factors might be important in some
diseases such as cancer. Some genomic tests might also reduce
the need for animal testing, for example of drug toxicity.
The most important recommendations for further advances
in this field were more support for research, more focus on disease
prevention rather than treatment, and more thoughtful regulation
and information on genetic testing.
Session 2: Translation to Clinical Care I
Presentations by Dr Mark Guyer, Director
of Extramural Research, NHGRI; Dr Adam Felsenfeld, Programme
Director of Large Scale Sequencing, NHGRI; Dr Leslie Biesecker,
Chief and Senior Investigator, Genetic Disease Research Branch,
NHGRI; and Dr Muin Khoury, Director, National Office of Public
Health Genomics, Centres for Disease Control and Prevention.
Dr Guyer described the establishment of the
National Human Genome Research Institute (NHGRI) as a change from
a cottage industry to the efficient generation of a comprehensive
catalogue of genomic information, with pre-publication release
of data and very large-scale projects based on close international
collaborations. Since completion of the human genome project in
2003, the NHGRI's mission had expanded and focussed on understanding
the structure and function of the human genome and its role in
health and disease. NHGRI had awarded substantial grants in genomics;
one example that had yielded fruit was the cancer genome atlas,
a partnership with the National Cancer Institute, funded at the
level of $100 million over three years. The project had already
obtained significant results on the genetic basis of several cancers.
Dr Felsenfeld explained the design and progress
of the 1000 Genomes Project, seen as a follow-up to the present
range of GWAS. The 1000 Genomes Project was an international collaboration
between the UK Sanger Institute and genome institutes in Beijing,
Texas, Boston and Washington. The project would sequence the genomes
of up to 500 people in each of three populations in Europe, Africa
and East Asia. The advances brought about by this project would
provide a complete catalogue of DNA sequence variation across
several populations and a catalogue of much rarer types of variation
than was hitherto possible. Data storage and transfer was a great
challenge. It was anticipated that the 1000 Genomes Project and
parallel projects in medical sequencing would identify many new
sequence variations that underlie disease and would be medically
Dr Biesecker described the ClinSeq project and
how major advances in DNA sequencing could provide benefits for
individual patients in the clinic. Using examples such as the
genetic diagnosis of patients with high cholesterol, he described
how sequencing medically relevant genes could help medical research
and treatment of patients.
Dr Khoury talked about the advances in genetics
of common diseases in the context of four phases from transitional
biomedical research to the clinic. Most discoveries became stuck
at the second stage, the point at which evidence-based practice
guidelines were developed. He emphasised the importance and strong
evidence base of conventional public health, for example treatment
with statins and aspirin for prevention of coronary disease, compared
to the lack of evidence of clinical utility in the use of newly-discovered
genes for common diseases for treating or preventing disease.
He described several studies currently at an early stage which
were designed to determine clinical utility of genomic testing.
He cautioned against premature translation of genetic testing
without an evidence base.
It was recognised that it was easier to generate
sequence data than to interpret that data and that whilst part
of this was an informatics problem, the lack of prospective studies
was also a major barrier to realising clinical utility. It was
emphasised that conventional risk factors such as body mass index
and cholesterol should lead to good advice about diet and exercise,
while genetic testing in the context of newly discovered common
disease genes might not add significantly to existing advice on
disease prevention that was already given to patients. The major
benefits of new disease gene discovery are likely to arise from
the ability to develop new drugs based on novel targets. Genetics
was a very fertile area of clinical research that could lead to
clinically relevant advances, for example in increasing efficacy
of drug prescribing. However many of the relevant clinical trials
had not been carried out to date.
Session 3: Translation to Clinical Care II
Presentations by Dr Linda Avey, Co-Founder
of 23andMe (via teleconference); Dr Dietrich Stephan, Co-founder
of Navigenics and Director and Senior Investigator, Translational
Genomics Research Institute (TGen); Dr Larry Brody, Senior
Investigator, Genome Technology Branch, NIH; and Dr Amy Miller,
Public Policy Director, Personalized Medicine Coalition.
Dr Avey described her role as co-founder of
23andMe in setting up genomic tests sold direct to the public.
She described services such as "chromosome painting",
a graphical tool to illustrate ancestry; "family tools",
a tool for graphically displaying information about inheritance
across the genome; other tools for specific genes for attributes
such as circadian rhythm and alcohol flush; and genomic profiling
tests giving information on susceptibility to individual common
diseases. For example, for type 2 diabetes, their tests indicated
the relative risk of developing disease based on results from
up to 30 low penetrance genes compared to the average risk of
the population. The company provided an email counselling service
which dealt mostly with technical or ancestry questions. They
worked with national genetic counsellors rather than offering
an individual genetic counselling service.
Dr Stephan, founder of Navigenics, talked about
the activities of his company in providing genomic profiles direct
to the public. The company provided a comprehensive service from
customer acquisition of samples to generation and interpretation
of test results via a personalised web portal, as well as ongoing
update services for customers and academic partners. The company
philosophy was that the private sector played a critical and necessary
role in disseminating research findings, which was not at odds
with responsible provision of a quality service. He expressed
the view that these technologies could provide substantial savings,
for example in prevention of Alzheimer's disease and type 2 diabetes.
The Navigenics laboratory had stringent quality control measures
that were provided in the context of national accreditation schemes
and education programmes for physicians and customers. The company
worked with the Personalized Medicine Coalition in encouraging
public and professional participation in the company's activities.
This included access to genetic counsellors within the Navigenics
service and the desire to work within statutory and other regulations.
Dr Brody discussed whether the state of the
science was ready for personalised medicine now or if it was too
early. He included within his definition of personalised medicine
the opportunity for individual diagnostics, pharmacogenetics risk
assessment and modification, and development of new drugs. Genetic
testing could be compared to other promising interventions such
as early lung cancer detection by chest x-ray and treatment of
back pain with early disc surgery. An important question was whether
individual test results from research studies should be fed back
to research study participants. As part of the Multiplex project,
Dr Brody had studied 2000 participants tested for 15 genes
in eight health conditions. Approximately half of those who took
part in the study wished to receive their test results. The proportion
taking part was lower in African Americans than white Americans.
As with other healthcare interventions, reaching certain segments
of the population would be difficult. To realise significant potential
for healthcare impact at the population level it was important
to learn from studies in practice.
Dr Miller described the activities of the Personalized
Medicine Coalition in educating policy makers and healthcare leaders
about the opportunities for personalised medicine. With a wide
membership from the commercial, academic and public sectors, the
Coalition aimed to provide opinion leadership on public policy
issues, to help educate public policy makers, government officials
and the private sector about benefits of personalised medicine,
and to serve as a forum for information and policy development.
Areas of activity included the combined use of genetic testing
with drug treatment, working with the FDA to change labels on
pharmacogenetic tests, and discussions with international colleagues
in the US, UK and elsewhere on optimum methods of regulation and
development of diagnostic tests. She described tensions between
the commercial diagnostic and pharmaceutical sectors, and anxieties
of US pharmaceutical companies about meeting recommendations of
international bodies such as the UK National Institute for Health
and Clinical Excellence (NICE).
A major difference between genetic and conventional
risk factors was that conventional, environmental risk factors
could be modified whereas as genetic factors could not. The view
was expressed that the use of currently known genetic variants
as part of genetic testing to predict development of common diseases
did not add substantially to risk prediction by using conventional
risk factors. Public demand for genetic tests was acknowledged
to be growing, but commercial products in this area had only been
launched very recently. It was recognised that the benefits of
early intervention in diseases such as Alzheimer's disease were
based on assumptions rather than an objective evidence base.
Tour of NIH Chemical Genomics Centre
Presentation by Dr Christopher Austin, Director,
NIH Chemical Genomics Centre.
Following a tour of the Chemical Genomics Center,
Dr Austin gave a presentation in which he described how the
Center had been founded in 2004 and now comprised 54 scientists
including biologists, chemists, informaticians and engineers,
who collaborated with more than 100 investigators world-wide and
had the capacity to screen more than 250,000 compounds in their
collection. The strategy was to bridge the gap between basic science
discovery and commercial drug development in the pharmaceutical
industry. Some discoveries had already reached commercial viability,
for example a compound shown to be useful for the treatment of
schistosomiasis. It was anticipated that the activities and strategy
of the Center would reduce the cost, shorten the time, and improve
the success rate in screening of lead compounds for drug development.
Session 4: Regulation and Policy I: General
Presentations by Dr M.K. Holohan, Health
Policy Analyst, Office of Policy, Communications and Education,
NGHRI; Dr Derek Scholes, Government Relations Manager, American
Heart Association; Dr Louis Jacques, Director, Division of
Items and Devices Coverage, Centers for Medicare and Medicaid
Services; and John Bartrum, Associate Director for Budget, NIH.
Dr Holohan gave an overview of the Genetic Information
Non-discrimination Act of 2008 (GINA), a federal law that prevented
health insurers and employers from discrimination based on an
individual's genetic information. GINA, which had been heralded
as the first major new civil rights bill of the new century, prohibited
health insurers from requiring genetic information or using it
in decisions regarding coverage, premiums or pre-existing conditions.
It also prohibited employers from requiring genetic information
or using it for decisions regarding hiring, firing or any terms
of employment. However, GINA did not apply to life, disability
or long-term care insurance.
Dr Scholes classified genetic tests into four
categories: tests for single-gene disorders such as cystic fibrosis,
multi-gene tests for chronic diseases such as cancer, tests that
aided disease management such as those carried out to ascertain
the correct dosage for blood thinners, and lifestyle type testing
such as nutrigenomic tests and those for addictiveness to tobacco,
etc. He highlighted three regulatory gaps in relation to genetic
tests: (1) measurement of analytical validity (the extent to which
a test was accurate and reliable) was not a requirement and was
not assessed for all tests; (2) the majority of tests came to
the market without FDA approval as they were developed in individual
laboratories and therefore had exemption; and (3) scientists and
administrators questioned the usefulness of many tests on the
The Laboratory Test Improvement Bill was currently
being considered by Congress and the Senate although it was unlikely
to be passed during 2008. The bill provided for FDA oversight
of all laboratory developed tests, an FDA public registry of tests,
and the submission of analytical and clinical validity data to
Dr Jacques described the Medicare programme.
It was a national programme with 54 million subscribers in the
US, mostly over 65. The Social Security Act stated that payments
should not be made for prevention and screening, only for curing.
Therefore predictive or pre-symptomatic genetic tests and services,
in the absence of past or present illness in the beneficiary,
were not covered under Medicare rules. Dr Jacques anticipated
that Medicare was due to run out of money by 2019. The programme
was administered region by region; therefore some services were
available in one region and not in others. Ten percent of coverage
decisions in Medicare were national and 90 percent were regional.
Mr Bartram explained the federal budget process
of the NIH from its conception all the way to the President's
signature. Different NIH departments had five year plans to identify
trends. Most of the NIH budget was spent on the 10,000 grants
given out each year with an average duration of three and a half
years. The total programme budget was $29.5 billion and it had
been flat for the past three years. Mr Bartrum highlighted
two challenges in order to maintain the US as a pre-eminent force
in biomedical research: the loss of purchasing power and ageing
equipment and supplies.
Physicians would be put in a difficult position if
they were asked by patients not to include genetic test results
in their medical records. Including life, disability and long-term
care insurance under GINA would have been better for individuals,
but it had taken 13 years for GINA to become law and if other
types of insurance had been included it would have been almost
impossible for it to have been passed.
Legislation of genetic tests had taken a long time
to reach the statute book. Legislators prefered statutory protection
as opposed to a code of practice, such as the UK insurance Moratorium,
as the latter was not enforceable. New York State had prohibited
direct-to-consumer tests and therefore an American company could
not sell such products in that State.
Medicare did not see sufficient benefits for patients
to justify payment for most genetic tests. If an individual were
tested for the BRCA1 and BRCA2 mutations and then
developed breast cancer, Medicare would pay for the treatment
but not for the tests.
Session 5: Regulation and Policy II: Oversight
of Genetic Testing
Presentations by Gail Javitt, Law and Policy Director,
Genetics and Public Policy Center; Dr Phyllis Frosst, Senior
Science Policy Analyst, NHGRI; Dr Steve Gutman, Director
of the Office of In Vitro Diagnostic Device Evaluation and Safety,
Food and Drug Administration (FDA); and Judy Yost, Director, Division
of Laboratory Services, Centers for Medicare and Medicaid Services.
Ms Javitt talked about the Genetics and Public Policy
Center at Johns Hopkins University. Certain goals were required
in the oversight of genetic testing in order to achieve public
confidence. These included ensuring that laboratory testing was
of high quality, and that tests carried out were clinically valid
and made truthful claims about tests' benefits and limitations.
Oversight should encompass development of new tests to avoid delaying
their translation into clinical practice. Continuing oversight
of genetic tests would require new laws as current regulation
did not fit the new context and technology continued to move rapidly.
The regulatory status of genetic tests depended on
how the laboratory developed and performed the test. If the test
was sold as a test kit or system then FDA had oversight of that
test because it was classified as a medical device. By contrast,
if a test were developed by a laboratory and carried out at the
same laboratory FDA regulation was not required. At present most
genetic tests were laboratory-developed and therefore clinical
validation was not required.
Dr Frosst gave an overview of the Secretary's
Advisory Committee on Genetics, Health and Society (SACGHS). One
of the activities of SACGHS was to identify gaps in the US system
of oversight of genetic testing, and to make recommendations about
how those gaps might be filled. Their report "US System of
Oversight of Genetic Testing" was published in April 2008
and called for more oversight of genetic testing, citing "significant
gaps" in validating the tests' usefulness, especially those
sold direct to consumers. The SACGHS also recommended "to
enhance the transparency of genetic testing and assist efforts
in reviewing the clinical validity of laboratory tests",
and that the Department of Health and Human Services should appoint
and fund a lead agency to develop and maintain a mandatory, publicly
available, web-based registry of laboratory testing. The SACGHS
also called for the creation of a public-private partnership to
evaluate clinical utility of genetic tests.
The Food and Drug Administration (FDA) was a government
regulatory agency that helped ensure the safety and effectiveness
of cosmetics, foods, drugs, and medical devices under the Federal
Food, Drug, and Cosmetic Act. The Office of In Vitro Diagnostic
Device Evaluation and Safety regulated all aspects of in-home
and laboratory diagnostic tests (in vitro diagnostic devices (IVDs)).
The standardised road map for evaluation assessed analytical performance,
clinical performance and labelling. Although laboratory-developed
tests were subject to CLIA (Clinical Laboratory Improvement Amendments,
administered as part of Medicare), only some are considered medical
devices by the FDA. Therefore the majority of laboratory developed
tests were not required to carry out clinical validation or pre-market
review and there were no post-market reporting requirements. Laboratory-developed
tests, the most common path for genetic tests, had a less burdensome
path to market and this could be the source of inadvertent or
deliberate abuse, including in the development and marketing of
The objective of the CLIA program was to ensure accurate,
reliable and timely laboratory testing. The requirements were
minimal and were based on test complexity. Most genetic tests
were categorised as high complexity. The programme was funded
entirely by user fees, not government, and covered all testing
on human specimens for health assessment within the 200,000 enrolled
laboratories. Under CLIA, no specific evaluation for genetic tests
existed because genetic testing was considered such a dynamic
area that prescriptive standards would be quickly outdated and
would lock laboratories into outmoded compliance. CLIA did not
cover clinical validity, utility, or claims made by direct-to-consumer
The definition of what tests needed FDA approval
was clear and was not necessarily determined by whether a test
was viewed as genetic or non-genetic. Some direct-to-consumer
testing companies claimed that they only provided genetic information
and not medical information.
The number of genetic tests sold directly to the
consumer was currently around 30, but this number was increasing
weekly. There were around 24 companies that provided direct-to-consumer
tests over the Internet.
Professional bodies were traditional in their approach
and broadly opposed to regulation. There was no equivalent of
the UK Genetic Testing Network (UKGTN) in the US and the FDA or
CLIA had no contact with UKGTN.
Session 6: Bioinformatics
Presentations by Samuel Aronson, Executive Director
of Information Technology, Harvard Medical School; Dr Peter
Good, Program Director, Division of Extramural Research, NHGRI;
Dr Jonathan Pevsner, Director, Bioinformatics Facility, Kennedy
Krieger Institute; and Elizabeth Humphreys, Deputy Director, US
National Library of Medicine.
Dr Aronson described the goal of the Harvard
Medical School Partners Healthcare Center as providing an information
infrastructure that improved patient care by enabling clinicians
to use the increasing amounts of genetic and genomic data that
were relevant to healthcare. Clinical decision-making by the physician
was based on ordering genetic tests in a consultation lasting
on average 14.7 minutes. The goal was to make widespread data
sources including personal medical and genomic information available
in a clinically readable format. The cost of DNA sequencing had
dropped dramatically in recent years with the $1,000 genome expected
to be reached in 2015. At that time, it would be possible to apply
a genotyping model to clinical practice, using a broad spectrum
test for general use including sequence data of hundreds of thousands
to millions of variations for each patient, which would be stored
in a repository and routinely accessed to understand the implications
of a patient's genome. When this model came to clinical practice
the need for bioinformaticians would be enormous.
The NHGRI spent 13.5 percent of extramural funds
in informatics, which amounted to $53 million in 2007. There were
two strands of spending: resource projects, such as model organism
databases, data standard and protein/pathway databases; and technology
development (research), or how to extract information from genome
datasets. The NIH roadmap identified bioinformatics and computational
biology as a key area. However there were many challenges ahead:
the production of increasingly large amounts of data; new technologies,
and new data analysis methods; funding for resources; lack of
recognition of computational biologists; and training.
Dr Pevsner defined bioinformatics as the interface
of biology and computers, essentially the analysis of proteins,
genes and genomes using computer algorithms and databases. Genomics
was the analysis of genomes, including the nature of genetic elements
on chromosomes. Bioinformatic tools were used to make sense of
the billions of base pairs of DNA that were sequenced by genomics
projects. There were great challenges when creating a disease
database such as the difficulty in organising the data by genes
or by disease; the complexity of disease mechanisms which were
not readily captured; the often obscure connection between a gene
and a disease; and the difficulty in estimating false positive
and false negative error rates. A major ongoing challenge was
to find ways of joining disease databases and DNA databases, and
how to ensure that specialists from different disciplines such
as computer programmers, biologists, clinicians and biostatisticians
could use their combined expertise to extract the required information
from databases containing different types of information.
The National Library of Medicine (NLM) had a budget
of $329 million and employed 1,330 staff and contractors, half
of whom worked in bioinformatics. Their goals included seamless,
uninterrupted access to expanding collections of biomedical data,
medical knowledge and health information, and integrated biomedical
clinical and public health information systems that promoted scientific
discovery and speeded transition of research into practice. Ms
Humphreys gave examples of databases that the NLM sponsored or
The best health care computer systems had evolved
over time and had included bioinformaticians from the beginning.
The major challenge was for the public to trust the data being
centrally held rather than stored in local doctors' surgeries
and hospitals. Due to the health care system in the US there was
little appetite for a centralised record centre. However, natural
disasters such as hurricane Katrina had prompted people to start
thinking about a centralised system. The Committee was told how
when Katrina struck, people's medical records were lost and those
individuals in the middle of, for example, cancer treatment found
great difficulties in continuing their treatment.
Session 7: Miscellaneous
Presentations by Dr Laura Rodriguez, Senior
Advisor to the Director for Research Policy, NHGRI; Jean McEwen,
Program Director, Ethical Legal and Social Implications, NHGRI;
and Dr Raju Kucherlapati, Scientific Director, Harvard Medical
The Committee heard that the greatest public benefit
would be realised if data from GWAS were made available, under
terms and conditions consistent with the informed consent provided
by individual participants, in a timely manner and to the largest
possible number of investigators. Dr Rodriguez explored some
of the ethical and policy questions during her presentation, for
example, should individual results from basic GWAS be returned?
How were the wishes of the individual participants respected?
How could the public's trust be sustained? And what level of de-identification
provided adequate confidentiality protection to participants without
damaging the science? Immediate and unfettered access to all qualified
users provided maximum opportunity for scientific progress. Confidentiality
of research participants should be protected and their consent
provisions respected. Equally, the need of investigators for academic
recognition should be recognised. There was consensus that GWAS
data should be released to the public at the earliest stage and
be available for use by all.
Dr McEwen gave the Committee an overview of
the different approaches possible when returning results to participants
in genetic research studies. She discussed three different approaches:
to disclose (almost) nothing, to disclose (almost) everything
and a balancing/contextual approach. It was key that this issue
should be considered carefully from the outset of the research
and communicated to the relevant ethics committee so that the
appropriateness of the plans could be assessed. Such plans could
be communicated to participants as part of the informed consent
process. In the context of these areas of debate, there was a
clear consensus that there was a need for more social/behavioural
research in this area.
Dr Kucherlapati highlighted the view that personalised
medicine would revolutionise the way medicine was going to be
practiced. However, there was a need for a shift in emphasis towards
prevention and better strategies for early detection. For existing
drugs and treatments, it was necessary to show that incorporating
genetics and genomics in clinical decision making resulted in
better outcomes. Regulatory agencies would need to take bold steps
for implementation of personalised medicine and a comprehensive
training and education plan would be needed.
Most new drugs were being developed in parallel with
identification of biomarkers that predicted drug efficacy. These
biomarkers could be developed into tests, the use of which might
then become the norm. The cost of drug development should not
increase because clinical trials that included a test of efficacy
would be quicker and less expensive. Cohort size could therefore
be smaller because efficacy and success rates would be higher.
This approach could also bring into the market drugs that might
otherwise have been shelved because of the low efficacy rate.
The use of biomarkers in clinical trials may therefore increase
efficacy to acceptable levels.
Genetic education would probably take place within
individual specialties, because genetic counsellors currently
mainly provided support for rare diseases and could not cope with
the volume of counselling required for common diseases. Tools
for online genetic education of healthcare professionals had been
developed at Harvard and were potentially available worldwide.
Session 8: Training Needs in Genomics
Presentations by Joann Boughman, Executive Vice
President, American Society of Human Genetics; Holly Peay, Associate
Director, Genetic Counselling Training Program; Dr Jean Jenkins,
Senior Clinical Advisor to the Director, NHGRI; and Professor Michael
Rackover, Program Director and Associate Professor, Physician
Assistant Program, Philadelphia University.
Dr Boughman described the different specialties
and certifications available in the US, and the membership of
the three main professional bodies that formed the genetics community:
the American Society of Human Genetics; the American College of
Medical Genetics, formed of practitioners of genetics; and the
American Board of Medical Genetics, with certified professionals
amongst their membership. There were great challenges ahead when
training professionals in genetics: the knowledge and technologies
were fast moving; 30 percent of Board-certified Genetics posts
were not filled; and the integration of genetics into health care
was driven by both consumer/patient demand and cost considerations.
Health professionals were the ultimate arbiters of how and when
(and if) new technologies and practices were integrated into health
The mission of the National Coalition for Health
Professional Education in Genetics (NCHPEG) was to promote health
professional education and access to information about advances
in human genetics to improve the health care of the nation. They
also provided a central educational resource for all health professionals
and developed tools to educate health professionals and incorporate
genetics into clinical practice. Their educational resources covered
general guidance, such as core competences and principles in genetics,
as well as specific topics, for example genetics and psychiatric
disorders. Their audience was wide-ranging, from nurses, family
physicians and physician assistants to dieticians. Ms Peay highlighted
crowded curricula, inadequate representation of genetics on certifying
exams, misconceptions about genetics, and lack of knowledgeable
faculty as barriers to genetics education for health professionals.
Ms Jenkins talked about the current genetic/genomic
education priorities and progress in nursing. There were 2.9 million
practicing nurses in the US in 2004 and of those only 26.6 percent
were under 40 years of age. Most faculty and practicing nurses
have had no genetics or genomics education or training and genetic
and genomic content was inconsistently incorporated into entry
level nursing programmes and licensing exams. Ms Jenkins described
a number of initiatives designed to increase genetic/genomic knowledge
in nurses such as the development of core competencies and agreeing
education priorities with the main stakeholders.
Professor Rackover gave an overview of the Physician
Assistant (PA) profession in the US and their training in genetics
and genomics. PAs were licensed to practise medicine under the
supervision of a physician. The United Kingdom did not have an
equivalent profession. Through various programmes and initiatives
the Physician Assistant Education Association achieved a substantial
increase in genetics enhanced curricula in PA training.
Public education was an area of the NIH that needed
greater emphasis. A range of activities was taking place but public
education programmes were not as robust as would have been ideal.
Tools for educating the public about family history had been developed
by the Surgeon General, the NIH and the Centers for Disease Control.
In certain areas the church could be a barrier to
public education, in pre-natal testing for example. Some faiths
such as Mormonism or Judaism had considerable emphasis on family
history which was a rich source of medically relevant information.
Some stand-alone training modules were described that were designed
to train general physicians in analysing the medical significance
of family history.
The scale of the training needs was huge because
the number of healthcare professionals who were in contact with
patients was very large and included general practitioners, nurses,
genetic counsellors, etc. The quickest way of introducing genetics
into the curricula was through the assessment system, but progress
was inhibited by curricula being set locally by each medical school.
If more genetics content was placed in mandatory exams, students
would be compelled more rapidly to study genetics, but it would
require medical geneticists to take on this task.
Session 9: Miscellaneous
Presentations by Dr Lawrence Lesko, Director,
Office of Clinical Pharmacology, Center for Drug Evaluation and
Research, Food and Drug Administration (FDA); Sharon Terry, President
and CEO, Genetic Alliance; Professor Christine Seidman, Departments
of Medicine and Genetics, Harvard Medical School; and Dr Greg
Downing, Program Director, Personalized Health Care Initiative,
US Department of Health and Human Services.
Dr Lesko described the activities of the FDA
in giving approval to new drugs, and the opportunity for genomic
knowledge and applications to be useful in new drug development
and in improved use of previously approved drugs. He described
the personalised healthcare initiative of the Department of Health
and Human Services Secretary, Mike Leavitt, aimed at providing
a conceptual foundation for policies in genomic medicine and pharmacogenomics.
He drew attention to the fact that FDA approval for new drugs
could be gained with only 30 percent efficacy and that genomic
testing had the potential to increase these low efficacy rates.
The FDA gave advice and instruction on labelling of drugs and
Dr Lesko gave examples of recent changes in labels of drugs
used in cancer therapy, lipid lowering and treatment of duodenal
ulcer. Genomic tests were currently required for the prescription
of six drugs, and recommended for a further six drugs.
Ms Terry described the founding of the non-for-profit
organisation "Genetic Alliance" following the birth
of her two children with the single-gene disorder pseudoxanthoma
elasticum. She was listed as a co-discoverer of the gene for pseudoxanthoma
elasticum and co-author of the Nature Genetics paper describing
this discovery. The Genetic Alliance had patented the discovery
of this gene and given all rights to the foundation in order to
have stewardship of the discovery. The involvement of patients
in biomedical research, and particularly the use of patient advocacy
in drug trials was an important part of the Alliance's mission.
Professor Seidman discussed the opportunities
and barriers with regard to genetic testing and heart disease
in the context of an increasing prevalence of heart failure within
an ageing population. She pointed out that interventions such
as use of implantable cardiac defibrillators were driven largely
by the funding available from insurance companies, and that genetic
testing could lead to much more efficient use of such devices.
She described the ways in which genetic screening could be applied
effectively, particularly since the introduction of GINA into
statute which had significantly advanced the opportunities for
use of genetic testing in research and clinical practice.
Dr Downing described the vision of the Health
and Human Services Secretary Mike Leavitt in moving towards personalised
healthcare. Policy had been established in three main areas: research
and development in genomic and molecular medicine; adoption and
networking of health information technology; and accelerated development
and use of a genomic evidence base. A two year time-line for personalised
healthcare had been developed that included improved delivery,
data integration, improved health information technology, and
expansion of the science base. Policy actions already in place
included an executive order in 2004 to establish a priority for
electronic health records and the signing into law of GINA in
2008. GINA aimed to prevent discrimination in employment and health
insurance coverage. Recommendations were also being drawn up to
develop a plan for genetic screening of newborn infants and for
use of pharmacogenetics tests.
It was recognised that newborn screening by genetic
tests was not a priority and that such tests could not be moved
easily from the place of testing. Moving information across States
was specifically prohibited. However screening for hearing disorders
was currently complete in 84 percent of newborn infants. Currently
screening was motivated by financial priorities but should be
evidence-based as it was in the US academic health science centers.
The small size of biobanks in the USA was noted compared to the
very large biobanks in other countries. It was pointed out that
work on systems for genetic testing was fragmented, with little
coordination across the wide range of common diseases for which
genetic testing was applicable.