Genomic Medicine: S&T Committee Report

Baroness Finlay of Llandaff Excerpts

Wednesday 9th June 2010 Lords Chamber

[Baroness Finlay of Llandaff]

My Lords, I was fortunate enough to be co-opted on to the inquiry and it has been a great privilege to work alongside so many people from a scientific background, many of whom sit on our Cross Benches. I congratulate my noble friend Lord Patel on his chairing of the committee and on his splendid introduction today.

I wish to speak about stratified or personalised medicine, the area of genomic medicine predicted to hold great potential for healthcare in the near term. It entails matching treatments to specific patients using clinical biomarkers to target treatments effectively by taking account of patient susceptibility to particular drugs or to adverse drug reactions. The Royal College of Pathologists told us that it anticipates that DNA and RNA-based diagnostic approaches,

“will guide more appropriate treatment and avoid ineffective treatment, and will identify some patients who do not need treatment. [They] will be an absolute requirement before the administration of many new treatments, especially new anti-cancer drugs; [and] will increasingly allow the prior prediction of severe adverse [drug] reactions”.

However, doing the test is not enough; it is the clinical context that is crucial. Therefore any thoughts that over-the-counter tests could move things out of the clinical arena are misplaced. Tests can be misleading at best—but they can be worse than that if they are not conducted in a proper clinical context.

My noble friend Lord Patel has already spoken about the cancer treatments that have emerged indicating a likelihood of a response to drugs, particularly Herceptin and Iressa in breast and lung cancer respectively. It is worth noting that such testing has increased about threefold in the past two years.

However, there are problems surrounding, in general, the translation of research on pharmacogenetic tests into applications. At present there is little incentive for the pharmaceutical industry to develop the genomic tests because the business model relies on the consumption of a product—a rather blockbuster approach—to ensure a return on the substantial R&D investment which is needed to bring a drug to the market. However, stratified medicine targets a much smaller patient group and requires the development of accompanying tests, and these tests must be developed in parallel with the therapy itself.

Professor Sir John Bell suggested that,

“the delivery of a new set of genetic tools into the clinic has proved really difficult”.

One reason for this was that diagnostic companies could not be relied on,

“to do what is done in therapeutics, which is to demonstrate clinical utility”.

This was because,

“the cost of a clinical utility programme is such that, at the prices paid for diagnostics, they would never get the money back”.

We therefore recommended flexible pricing models for therapies that rely on the use of pharmacogenetic tests, the protection of intellectual property and the concurrent development and authorisation processes for therapies and diagnostic tests that will assess the clinical utility and validity of genetic and genomic tests within the NHS.

The previous Government’s response stated that the Department of Health had commissioned NICE to develop and manage a single evaluation pathway specifically for diagnostic technologies, with a pilot scheme due to report this summer. A new committee within NICE should ensure health technology assessments look at the clinical utility and validity of diagnostic tests. Can the Minister assure us that these developments are still on course? Can he clarify how the proposed value-based pricing system will allow targeted treatments to be more available, even if at a local level commissioning decisions do not support the necessary infrastructure? There may be a potential tension here between central promises and local sovereignty in decision-making.

This is particularly important when evaluating diagnostic tests. These are inherently more complex to evaluate and yet the funds for doing so are relatively trivial. Commissioners do not know when to invest in expensive testing equipment if its utility and validity has not been assessed, and so silo budgeting acts as a barrier to capital investments, leading to a postcode lottery in diagnostics. Decisions need to be made at a national strategic level, not locally, and it is essential that clinical genetics departments are supported. They should be linked and pivotal to informing studies into the whole commissioning process. Can the Minister confirm that the Department for Business, Innovation and Skills is working with the Department of Health to ensure that intellectual property systems and management of intellectual property rights support diagnostic test development, evaluation and rollout as we recommended?

The research community is collaborating to realise the potential of the NHS for the benefit of all. The network of hospitals in the NHS is ideally placed to link with research bodies. Indeed, the funding bodies are doing just that. This year Cancer Research UK will begin to establish a network of NHS centres using similar genetic techniques to guide treatment decisions. It will be the precursor to treating every NHS cancer patient in a similar way, perhaps in as little as five years. However, other genetic tests have not been integrated properly into healthcare. Our committee heard of the patchiness of testing, as has already been alluded to, for conditions such as diabetes.

There is a lack of clarity over funding streams for the use of such tests as part of treatments within non-genetic specialties, and there are inconsistencies in the ordering of such tests during consultations. As I have said, doing the test alone is not enough; it is the clinical context that is key. Genetic testing is usually in the genetics department’s budget and so is not necessarily more widely available. The cost of testing is increased if the patient has to be referred to be seen in genetics rather than a treating clinician taking responsibility for the whole process. Meanwhile, genetics departments are increasingly taken up with the delineation of single gene disorders as a subset of common complex disorders, and with the co-ordination of care for those with single gene, multi-system complex disease. Genetics departments are already facing potential overload.

To ensure better use of drugs we need a red flag system of automated warnings rolled out to ensure that appropriate tests happen routinely. This will result in a cost saving through stopping inappropriate prescribing and inappropriate testing and avoid adverse reactions.

The area that concerns me most of all is the failure of the Human Tissue Act to promote single gene testing for single gene sudden death disorders that mean that many young lives are lost. For more than 20 years we have been able to perform gene testing in the family and make an early diagnosis in the family of a risk of sudden cardiac death. NICE recommended the testing but at a clinical level it is not readily available.

One problem is that there is no clear definition at post-mortem of “retention” for tissue samples, so, whether or not anything is seen macroscopically, samples are not always sent for DNA testing. If the family is not integrally linked into the process, samples can fall between pathology, genetics and the coroners system, and a diagnostic opportunity for others in the family can be lost. Will the Minister assure me that we will look urgently at this matter so that all patients who die of suspected sudden cardiac death will have tissue removed post-mortem for comprehensive DNA analysis? That will be linked to genetic support. Such testing should be for multiple genes, because it will save lives.

The UK Genetic Testing Network is meant to be undertaking a review of service provision within the NHS to inform a consistent approach for single-gene disorders and single-gene subtypes of common disorders. Does the Minister know when we can expect the Government's comprehensive assessment of this? I realise that it is difficult for a Government who have only just taken over something already in progress.

An extension of genomic medicine is epigenetics; that is, changes in the gene expression caused by mechanisms other than a change in the underlying DNA. The molecular basis of these changes is related to the packaging proteins known collectively as chromatin. The changes are not encoded in the genome sequence so are not generally passed from generation to generation. We are seeing ever more examples of underlying genetic links, such as the link with addiction, where it seems that the serotonin and dopamine in the brain’s reward systems may be linked in some people when other factors come into play with developing addictions. However, it does not mean that everybody with that piece of genetic code will necessarily become an addict.

Understanding these developments provides a “fantastic window” on different types of common diseases, but genetic counselling and genetic support are key if we are going to use any advances appropriately. I must declare an interest: I am at Cardiff University, which has one of only two established MSc courses in genetic counselling in the UK. It is well on its way to becoming an independent discipline.

We need to ensure that genetic testing and services are supported today to ensure that developments are used to best advantage when they appear tomorrow.