Memorandum by Professor Sir John Bell
I think it is very timely that the House of
Lords should be considering this extremely important topic because
the pace of chance in genetics and genomics as it relates to human
common disease has been extraordinary over the past two years.
There is no question that genetic and genomic information could
substantially influence the way healthcare is practiced and I
believe the UK and the NHS need to be prepared to introduce these
innovations in an effective and efficient way. There is already
a host of DNA or RNA based tests which are proving to be important
in the management of a range of diseases. DNA sequencing is becoming
an increasingly powerful tool for identifying individuals at risk
of major single gene disorders. These tools, along with transcript
profiling and microarray analysis, will be capable of influencing
the diagnosis and treatment of most of the common disorders managed
today in the clinic. New methodology for DNA based papilloma virus
screening could replace PAP smears very rapidly. I would like
to focus my comments on two issues: the organisation of molecular
pathology and genetic services within the NHS, and the management
of a structure for evaluating their utility and regulating their
introduction into practice.
Pathology and laboratory services in NHS hospitals
are severely fragmented and there is a serious risk that introduction
of a range of new technology platforms will lead to further duplication
in multiple different laboratory settings. Many of the technologies
necessary for moving pathology into a new era are the same as
those that would be used in clinical genetics laboratories and
will also have applicability to both microbiology and haematology.
There is an urgent need therefore to rationalise the management
of these, either at an NHS Trust level or through large regional
laboratories. These tools need careful technical support, bioinformatics
and quality control and it seems unlikely that these can be developed
in multiple sites within a hospital without undue costs. I think
the coalescence of these platforms within a single clinical service
structure is imperative to ensure that there is a coherent approach
to these methodologies within the NHS. We have achieved this in
Oxford using the Clinical Research agenda to drive integration
of laboratory' services. It should be replicated elsewhere.
Equally important is the mechanism for evaluating
the clinical utility of these tests before they are introduced.
It has not been customary in the past to evaluate the utility
of diagnostic tests but rather to simply evaluate the accuracy
of measurement of a particular analyte. This will no longer be
sufficient for regulation. It will also not be possible to easily
obtain clinical utility data as the pricing structure of the diagnostics
does not make such large evaluation studies economically viable.
Another difficult issue is that the information on a given chip
or device is likely to change iteratively as we go forward and,
as a result, a regulatory structure which identifies a pattern
genetic variants relevant to a disease cannot be regulated in
the conventional way. We need a new approach for regulation of
these diagnostics. It is unlikely that the heavy-handed approach
used by the FDA is going to be appropriate for diagnostics in
Europe. In the USA, by the time a diagnostic or platform finally
achieves approval—up to two years later—it will already
have been altered to include additional information that adds
further value and the approval process must be re-entered. This
has largely prevented tools from entering the market place in
a timely fashion and is also extraordinarily expensive. We need
to identify a new agency that can handle the clinical utility
evaluation of diagnostics using methodology fit for this purpose
including both randomised clinical trials and cohort type approaches.
This could act as the gate-keeper for the NHS. One alternative
would be to utilise NICE for this purpose, but much of the methodology
that needs to be used for clinical utility testing is different
from the conventional approaches for therapeutics and a distinct
structure is preferable. A specific HTA programme for diagnostics
is essential as the questions addressing problems associated with
diagnostics are very different from those associated with therapeutics.
Such a programme would provide information both for the regulatory
decision as to whether or not to license such technologies in
the NHS and, ultimately, could be used for more widespread approvals
internationally. It might even be possible to do business with
the diagnostics industry by providing them with an ideal platform
for evaluating their diagnostics within the NHS, to share the
risks and the costs of this process and to ensure a substantial
cost reduction to the NHS if these products were marketed globally.
These are difficult and challenging questions,
but I believe the sub-committee you are chairing will need to
look at both of these problems carefully as they will be important
in determining the success of introducing these innovative technologies
in the NHS in the near future.
I hope these comments are helpful.
17 April 2008
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