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Statement of the
Parent and Patient Organisations (EAGS)
The Necessity of Early Detection and Accurate
Diagnosis |
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Early detection and accurate diagnosis of diseases
accompanied by information
individually/group tailored
well balanced and timely
comprehensive, reliable and up-to-date
with appropriate guidance
and of course preferably followed by effective treatment
is a high and increasing priority for
us as patientorganisations
but also for Europe
The European health system of tomorrow will have to satisfy
the growing needs of the concerned individual to learn early,
well documented, his risks and his options regarding prevention
and therapy.
1. The Promise of In Vitro Testing
Information about the body can be obtained in a number of
ways: by imaging and scanning to get morphological and functional
information, by physical measurements of temperature and weight
etc., by electro-medical measurements such as ECG or EEG and
by the measurement of biochemical and genetic parameters using
in vitro tests.
There is a need for more effective use of in vitro testing
to provide early and correct diagnosis as the foundation for
effective treatment: early diagnosis because it is in the
interest of the individual concerned to detect disease at
an early stage when chances of cure are highest, and correct
diagnosis because a wrong diagnosis inevitably means ineffective
treatment, and no diagnosis often means no treatment. Early
diagnosis can also be of interest for primary or secundary
prevention by familiyplanning and lifestyle issues.
However, in vitro tests are not just used for diagnosis.
They also provide objective information that forms the basis
for better medical decision making. It is this informational
aspect that differentiates in vitro tests from other medical
devices that are used to treat patients. It is no longer sufficient
to give treatment without closely monitoring the result in
the individual treated. In vitro diagnostic testing has an
important and increasing role to play in monitoring the treatment
given to individuals to determine if it is having the desired
effect - this is called "theranostics".
Early testing and acurate diagnosis can make a vaste contribution
towards a new paradigm: healthmaintenance beside the old paradigm
of disease management.
2. The Reality of Diagnosis
Individuals and their families who are affected by genetic,
multi-factorial and/or chronic disease have often experienced
late and often vague diagnosis. In their experience, many
physicians do not understand or utilise the breadth of laboratory
testing options that are now available. In 1998, a survey
of knowledge about in vitro testing undertaken by Watson Biomedical
in the United Kingdom showed that physicians have a general
lack of awareness of in vitro tests.
Individuals have often experienced that not only is information
about the tests and the diagnosis limited, it is poorly communicated,
and that support for the implications of the diagnosis and
for coping with the disease is scarce and difficult to find.
Rather than just providing data, more information needs to
be made available to healthcare providers to allow for easier
interpretation of results.
Physicians also are not always aware of what it means to
live with the reality of an undiagnosed or untreated disease,
while individuals, on the other hand, are often unaware of
the advantages of knowing their diagnosis and how to use this
information to plan or even to improve their future quality
of life.
Finding out whether someone is at risk for a particular genetic
condition can be important to help them to plan preventive
measures or help them to make better decisions about their
future. The following examples illustrate the necessity for
early and accurate diagnosis of illness and disease.
| (a) |
There are reports of families with three or more children
suffering from the same deteriorating disease, born one
after another. These parents were not warned about pre-conceptual
screening or given genetic counselling early enough after
the birth of their first child, and because Duchenne's
muscular dystrophy manifests itself around the third or
fourth year of life, had further affected children. This
X-linked muscle wasting disease can be detected by a simple
CK bloodspot test at birth. |
| (b) |
A father signs a contract for a job hundreds of kilometers
from home and soon after hears that his three year old
daughter who has suffered health problems since birth,
has finally been diagnosed with a progressive metabolic
disease that will require his presence and time at home.
The disease could have been detected at birth and the
father would not have signed a contract to work so far
away. |
| (c) |
A family bought an apartment on the fourth flour in
a building without a lift. A short time later, their child
developed a progressive paralysing spinal muscular atrophy.
If the disease had been detected earlier, the family would
have found a more suitable housing arrangement. |
| (d) |
A man, after many years of worrying, applied to a medical
help desk, explained his concerns about various members
of his family dying at about age forty and inquired about
his own risks of early death. Subsequently, he discovered
that his family members who had died had suffered from
the cardiac problem Familial Hypercholesterolemia (FH).
This individual learned about FH, and took the information
to his doctor. He underwent genetic testing and was diagnosed
with the same problem. He was fortunate to be able to
receive treatment. |
3. Advantages of Early and Accurate Diagnosis
Accurate diagnosis eliminates uncertainty, reduces anxiety,
and prevents the costly, frustrating and time-consuming odyssey
of shopping through different healthcare systems. It allows
for early treatment and management of the condition. In the
case of a child born with a genetic disease it offers the
possibility of avoiding repetition within the same family,
protects the relationship between the parents, provides options
for future family planning and enables the family to make
appropriate life style choices.
As already stated, treatment is only one of many reasons
for early and accurate diagnosis. Screening and testing for,
as yet, incurable or untreatable diseases can be very relevant
for families. People should not be denied access to tests
merely because there is no medical or economic benefit, and
they cannot be reduced to their "treatability" in
the health care system. The information that in vitro testing
can provide should be supported rather than suppressed. One
should first ask if there is a benefit for the individual,
look at the clinical and medical benefits, and only then ask
the questions: Is it affordable and who should pay?
The question as to whether we can afford certain medical
interventions is an important but separate issue from the
fact that individuals may want to have certain tests done.
They may even be willing to pay out of pocket for the information
that will be provided. From the perspective of an individual
and his family, a negative test result and the assurance that
nothing is seriously wrong is extremely valuable information
that will reduce anxiety and uncertainty about the future.
On the other hand, others may find that the reverse is true,
and they would rather not know their test results.
Certainly, there is room to challenge the conventional thinking
that has led to present attempts to limit individual responsibility
for health. Health is a good investment, not just for us all
as individuals, but for society as a whole.
4. Requirements of Diagnostic Testing
Most laboratory tests in Europe are used in the management
of disease. Although there are a number of tests that could
be performed as part of health management, for example testing
blood cholesterol or lipoprotein levels as predictors of heart
disease, usually healthy people do not ask for such tests.
Factors that play a part in this choice are the inconvenience
of going to a medical laboratory or to the doctor's office
to have a test performed, and waiting for the result. Laboratory
tests today, can be developed in formats that are suitable
for public use and give rapid results.
When such self-tests are available, as has happened with
pregnancy tests, they tend to be well accepted and widely
used. In general, the public understands that tests can be
performed incorrectly, that they can require additional testing
before the result is certain and that the doctor may need
to be consulted. Even tests requiring blood sampling can be
developed into user-friendly formats for self-testing. Blood
glucose tests for monitoring diabetes is a good example of
this.
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Diagnostic self-tests must be designed specifically
for the type of person who is using them. For example
there may be special language requirements or a need for
a large visual display. Because lay persons are not expert
in using tests they may need extensive training and for
this reason it may be more expedient to encourage self
ordering of tests rather than self-testing. |
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Any diagnostic test should be accompanied by clear,
inclusive and well-balanced information that is specially
tailored for the layperson. Preferably, this information
should be produced in consultation with relevant professional
and patient groups. |
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A person taking a test should preferably consult with
a family doctor, specialist and/or counsellor. This is
advisable but should not be mandatory. Accessibility to
testing and information about testing is most important. |
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The person tested should have access to trained professionals
with appropriate support (e.g. a doctor, a nurse or a
counsellor) if results are outside the normal range, so
that they can be properly assessed and confirmation tests
taken if necessary. |
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Some genetic tests may require education and counselling
beforehand to ensure that the person being tested understands
the test to be done, the potential results of the testing
and other issues that may need to be considered. Counselling
sessions and/or support must be provided if test results
are confirmed to be unfavourable. |
Society should in no way contribute to:
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the infringement on the autonomy of the individual's
choice either to use or not to use tests. The individual
concerned must decide whether or not testing is appropriate
for him and whether or not he wants to know the results.
There should be no pressure placed on the individual to
choose, or not to choose testing. In addition, he must
decide whom, if anyone should have access to his test
results - including the doctor. There must be complete
freedom to make these decisions even in the event of conflict
without societal repercussions. |
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the concept that people with a disease or handicap are
considered as "cases of missed prevention".
There may be disadvantages for the individual. For example,
a diagnosis may label the individual diagnosed as a "medical
case" and societal pressure may decrease personal
freedom of action and choice. Rather than choosing to
have a therapeutic abortion for a pregnancy affected by
Down's syndrome, a family may decide instead, to carry
on with the pregnancy, have the baby and care for the
affected child. |
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the stigmatisation and discrimination because of the
decision to have diagnostic testing (including genetic
tests to determine future risks) or because of the decision
to decline testing. This specifically refers to banks,
employers and insurance companies. |
5. The Future of Diagnostics
In vitro diagnostic testing presents exciting opportunities
for the future.
Diagnostic testing is already highly technological and well
developed and the reality of the recent advances in this arena
is truly phenomenal. The Human Genome Project is forging ahead
and with the identification of new markers, the genetic background
for common disorders and rare diseases is being unravelled
and molecular biology is facing new dimensions. This is relevant
for rare diseases and common diseases such as diabetes, various
cancers, Alzheimer's disease, and different forms of heart
disease.
Thanks to the rapid advancements at the bio-molecular and
genetic level, the availability of tests for early, pre-symptomatic
detection and screening, for susceptibility and carrier status
for disease will continue to increase considerably and a wide
range of tests and self-tests will become more available.
These tests will be welcomed as they enable people to act
early according to their own wishes and needs.
New in vitro tests are already opening up a future of individualised
medication. These new advances are known as "genomics"
or "proteomics" depending on whether they are based
on genetic information or knowledge of the proteins involved.
New drugs are being developed to suit people who, on the basis
of in vitro tests, are shown to be receptive to treatment
and will allow selection of individuals that can tolerate
powerful drugs that, in other people, give intolerable side
effects. The prognosis and monitoring of such treatments is
dependent on laboratory information. Perhaps the most well
known example is the measurement of the HER-2 receptor to
predict whether breast cancer will be responsive to the medication
Herceptin.
In addition to the applications for developing genomic pharmaceuticals,
information from genetic tests can also be used by individuals
to make life style choices (e.g. those affected by Familial
Combined Hypercholesterolemia). This is part of the overall
trend towards empowerment of individuals, where emphasis is
placed on the prevention of disease, on health and on wellness
testing.
Information is becoming readily available to consumers as
well as health care professionals through the Internet - eHealth.
People are beginning to use this information to their advantage
because they can obtain comprehensive up-to-date health information
and access health care services (information about disease
prevention, diagnosis, and treatment options including laboratory
testing, self-care, interactive check-ups, etc.). It is reasonable
to say that relationships between their doctors will undergo
fundamental change. In fact, they may even consult with a
physician online before they see their own family doctor.
In contrast to this positive view of the future and increasing
demand for in vitro testing is the constant pressure to cut
the costs of the public health system. In fact, because the
marginal cost of performing in vitro tests can be very low,
additional information from IVD tests can be obtained at little
extra cost. On the other hand, increasing the amount of diagnostic
testing will no doubt have an impact on the demand for health
care and will be seen as creating a burden on the health care
systems of Europe. This means that, although a diagnosis may
be of great value to the individual and his family, it may
not be cost-effective for society as a whole.
In order to increase the value of medical interventions and
to select interventions with high quality in relation to their
cost, health economists and the medical professions increasingly
look at the evidence for the effectiveness of medical procedures
and practices. Objective information from in vitro testing
often provides the evidence that is needed in the growing
implementation of this Evidence-Based Medicine (EBM) approach.
One element of this approach is to look at new technologies
(medical procedures) and assess their utility before they
become routinely used. Here again much of the objective data
for Health Technology Assessment (HTA) may come from in vitro
testing.
6. Recommendations
Because of the ongoing developments of in vitro diagnostic
tests, society must be prepared for the new options brought
forward by molecular biotechnology and genetic knowledge in
order to optimally benefit from them. The application of such
tests requires continued surveillance and adjustment to improve
the quality of health care delivered to individuals. Attention
should be given in future to finding the genetic markers that
indicate predisposition to disease, not just for the informational
value this has for the individual, but also to be able to
select sub-populations for screening and treatment.
Scientists, industries, clinicians and patient organisations
must work together to provide and increase the availability
of reliable, effective, simple and inexpensive tests. This
can be achieved through stimuli and economic incentives for
researchers and for in vitro diagnostic test manufacturers,
a higher level of awareness of clinicians of available diagnostic
tests and clear and realistic expectations from individuals
and patient organisations.
This means ongoing education to all individuals, providing
flexible healthcare systems in which a knowledgeable public
can manage information and use it for their own benefit. Making
young people aware of their health status through education
and various health promotion activities with respect to the
wide range of simple laboratory tests may be an initial step
in this complex process.
It may also be necessary to establish a network of laboratories
at the European level in order to provide services that are
not available at the national level. The cost of testing must
be covered by each country's National Insurance or by the
hospital.
Finally, more study is required about the ethical, medical,
social and technical implications of screening.
SCREENING
Screening programmes set out to identify the risk of disease
or its complications in those individuals who are apparently
in good health. Screening programmes have the potential to
save lives and improve the quality of life through early diagnosis
of diseases, infections and other conditions from pre-conception
through to old age. However, people should have realistic
expectations about what it is that screening tests are able
to provide.
Screening tests are often performed on people without any
other indication of disease. All positive screening test results
must be followed up by other confirmatory tests and medical
consultation before any decisions about management or treatment
can be taken. Clearly it would be unwise to jump to any conclusion
on the basis of one test, without any supporting information.
With this in mind, screening tests can be very valuable both
to the individual concerned and to society as a whole.
Identifying a sub-population at risk (targeted screening):
One way to increase the reliability of the information obtained
in screening tests is to perform them at regular intervals
on individuals in a selected subpopulation at risk for developing
a specific disease. The costs of screening can be reduced
if the sub-population at risk can be identified and tested
instead of testing the whole population (e.g. PKU screening
of all newborns). This means, that if the sub-population is
sufficiently well identified by using a variety of risk factors
in combination, the test becomes more of a diagnostic or a
confirmatory test rather than a screening test.
Of course, in the context of a rare disease, the smaller
the target group is, the better. Compared to biochemical testing,
DNA-based tests should in reality have fewer false positives.
This is a great advantage to population and targeted screening.
With the knowledge and mapping of the human genome, we are
now able to screen targeted and entire populations for genetic
mutations.
In any screening test procedure, the result may indicate
that a person has the disease when in fact they don't. This
result is termed "false positive". Health economists
tend to look at whole populations when looking at the funding
of screening programmes. From this point of view, it is in
the interests of the hospital or treatment organisation to
make sure that everyone who has a positive test result actually
requires treatment ("ruling in" disease). They will
therefore try to ensure that the diagnostic tests used have
a low number of false positive test results, both for clinical
and for economic reasons. Population screening tests generally
require that false positive results be minimised. Whether
the disease is common or rare (whether the disease has a high
or low prevalence) does not make much difference in this situation
- it is the rate of false positives that is important.
The opposite may also happen - a person with the disease
may have a test result indicating no disease. This result
is termed "false negative". It is obvious that the
real interest for the individual who is tested is in knowing
with a high degree of certainty that he does not have a disease
or infection ("ruling out" disease). Therefore,
a good test for ruling out disease minimises the number of
false negative results.
Difference between population screening and the reality of
clinical practice: In screening tests, reliance is placed
on the total (diagnostic) specificity of a single test performed
once in a screening procedure. Clinical practice is quite
different. There is much more information available than one
test result per person. By combining the results of many different
tests with previous results along with clinical symptoms,
family history, etc., the overall specificity of the diagnostic
process is much increased. Because of this combination of
correlated results, the rate of false positives is much less
critical in clinical practice.
A specific test that successfully rules in disease may not
necessarily be in the best interests of the individuals tested,
because a negative result test does not rule out disease with
sufficient certainty. On the other hand, a sensitive test
most people might like to have to rule out disease may carry
the burden of an expensive follow up of a relatively large
number of false positive results.
An increasing amount of information about states of health
and disease can be obtained by performing sensitive and specific
in vitro diagnostic tests. Ideally, all diagnostic tests should
have these high standards of accuracy as well as reliability.
This situation represents a trade off and the provision for
a fine balance between the specificity and the sensitivity
of a test.
HIV screening of donated blood: A good example of a particularly
sensitive test used to rule out disease is HIV screening of
blood. In this case, the rate of false negatives must be kept
low not only for the sake of the individuals directly concerned,
but also because the donated blood is pooled and used to treat
many other people. Because of intense public interest and
the political pressure exerted, a lot of funding was made
available for test development.
It is worth noting that the safety of blood donation is also
increased by careful selection of donors to decrease the risk
of infection in the selected sub-population. As a result,
the false negative rate for HIV screening of blood donations
is estimated to be less than one in a million.
Because of fears concerning the potential costs of follow
up in screening programmes, governments tend to be very cautious
about recommending screening tests. However, it is in our
interest as individuals concerned with health that the various
forms of active screening for chances of risk of serious diseases
with options for treatment and/or prevention should be promoted.
Following are some examples of screening options:
| 1. |
Carrier Screening for Cystic Fibrosis (CF) |
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Cystic Fibrosis is an autosomal recessive disease
in which carriers of one copy of the defective gene
may have no symptoms of the disease. Children who inherit
two copies of a mutation may develop the disease with
varying degrees of symptom expression.
Because the epithelial cells in the body have an abnormal
cell transport function, they produce mucous and other
secretions that are much thicker than normal. These
thickened secretions cause problems mainly in the lungs
and, as well, block the flow of pancreatic enzymes into
the digestive system. This encourages bacterial lung
infections and also results in the malabsorption of
essential nutrients.
Currently no cure exists for Cystic Fibrosis. However,
the value of genetic testing for carrier screening has
been shown. It is known that the earlier the diagnosis
of CF is made, the better chance there is to improve
the symptoms and outcomes of the disease.
Pilot studies in the United Kingdom have looked at
the possibility of screening for CF carriers and have
tested various programme strategies. For example, they
have offered testing to pregnant women and if any woman
is identified as a carrier, then her partner is offered
the test. If the pregnant woman, however, tests negative,
then the question has been answered and carrier screening
of her partner is not needed. The child born to this
couple will not be at risk for CF. Carrier couples,
on the other hand, will be offered genetic counselling
and possible interventions.
Presently, DNA based technology is being used to screen
an entire population of prospective parents in the state
of Wisconsin in the USA through another pilot screening
project. Individuals and couples with no family history
of CF are being offered the screening test in order
to identify unsuspecting carriers of the defective gene
using a multi-mutation genetic testing panel that detects
31 mutations. It appears that CF diagnostics will continue
to maximise the quality of life for those suffering
from the disease. |
| 2. |
Familial Hypercholesterolemia (FH)
This is a common inherited lipid disorder with mutations
in the LDL receptor gene causing increased plasma control
levels of cholesterol. Untreated, this results in the
development of cardiovascular disease and premature
death. Maximum health benefits can be achieved if treatment
is begun early using lipid lowering medication in conjunction
with the monitoring of therapy.
The importance of providing information about this
disease prior to testing encourages individuals to participate
in screening programmes and become compliant with their
treatment and monitoring follow up. FH is frequently
under diagnosed and many of those who are identified
without DNA diagnostics are often not treated or monitored
appropriately.
In 1994, the Netherlands began a family screening programme
using both DNA analysis and cholesterol measurement
to actively identify and treat those individuals with
FH. This project has proven successful with the result
that funding for an expanded programme has been approved
for a further 10 years. |
| 3. |
Newborn Screening of Type I Diabetes
The American Diabetes Association has committed funding
to provide Type I diabetes screening to all infants
born in the state of Florida in the USA. This programme
will build on an already existing project, which began
3 years ago at the University of Florida and will start
in August 2003.
The goal of this programme is to follow children, once
identified with the genetic risk of developing diabetes,
to determine what environmental factors might trigger
this disease. Research into the prevention of these
triggers will happen concurrently. Those infants identified
as moderate and high risk for the development of Type
I diabetes will be monitored using micro-arrays to explore
tens of thousands of their genes. |
Y.S. Poortman, Brussel, 17 May 2002
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