David Weatherall finds that great promise needs much preparation

The concept of personalised medicines, where a person is prescribed drugs tailored to their genes, promises a future of safer and more effective medicines. But has this promise been over-hyped? And if tailored drug treatments become a reality, does the health service have the infrastructure and resources to put them into widespread use?

The Royal Society has published a report examining these questions. It concludes that an era of personalised medicines will not be with us for at least another 15 to 20 years.  This is mainly because there are still so many gaps in our understanding of what part genetics plays in the complex, multiple causes of disease.

The report also points to a handful of encouraging examples of personalised medicine being used in the treatment of cancer, illustrating the value of such an approach.

Background
Personalised medicine is known as pharmacogenetics – a term first used in 1959 to describe the discovery that variation in the function of a single gene can modify the effect of a drug. Since then it has been broadened to encompass how people’s total genetic make-up affects their response to medicines. This can mean recognising subsets of common diseases that can be treated differently, the identification of genes that make drugs effective or harmful and the use of differences in susceptibility to infectious diseases to develop new medicines or vaccines.

With the success of the human genome project and advances in our understanding of how both drugs and genes work, some people have high hopes that the next few years will see a revolution in the way patients are treated. Meanwhile, others have expressed reservations that pharmacogenetics, in its current form, can fulfil such promises within this timescale.

At the same time, the NHS bill for drugs is expected to reach £11billion for 2005-6 and roughly 1100 people a year are dying from adverse drug reactions. The health service would welcome any opportunity for increasing the effectiveness of drugs or reducing the risk of harmful side-effects by taking genetic factors into account.

Trials and support
What became clear in the report is that we need to know more. Funding is needed to conduct well-designed studies in pharmacogenetics to establish how well it can be applied to clinical practice.

For new drugs these trials will be conducted by industry. But for medicines already on the market, the onus will be on government to fund research. The government could deliver funds through the Medical Research Council and the Department of Health, for studies in partnership with both the medical charities and industry.

Key to this process will be ensuring that researchers are able to link patient records back to the individual’s genetic information. This will require access either to samples collected or genetic data already stored. The NHS is well placed to make this possible. In addition, DNA samples should be taken from as many clinical trials as possible, in order to facilitate trials of the genetic variability of patients’ response to drugs.

By analysing the data from clinical trials, researchers may identify groups of people with a particular gene or genes for whom a drug works, but which does not work in the wider population. Such treatments will have a very limited market, so the provision of tax incentives will be important in encouraging industry to participate.

There is also a role for industry in developing and producing diagnostic DNA tests, because accurate, easy-to-use and reliable tests will be essential for correctly administering the drugs. And if such tests are to become widespread, a regulatory framework needs to be set to make sure they are properly introduced and meet the required standard.

Monitoring should also continue once products are on the market with the aim of linking genetic variability with clinical outcome. This kind of work should be mandated at the national and European level as an extension to the current system of clinical trials.

National needs
The challenges facing the NHS in introducing personalised medicines, as they begin to filter onto the market, are immense. In the short term, training and awareness-raising among doctors and other healthcare professionals are needed, as few currently have a clear understanding of the area and the benefits it could bring to patients.

Scientists trained in the appropriate areas are needed to really progress this avenue of research. Clinical pharmacologists, biostatisticians and population geneticists will all be in high demand in both industry and academia. There are currently shortages in all these areas, so encouraging young researchers to specialise in these fields will become increasingly important. There were also concerns over the capacity of GPs to be sufficiently up to date with the technology to support widespread use and advise patients successfully.

The collection and analysis of patient data introduces issues of how to store the information securely, who has access to it and how far it is anonymised. There is public concern over these issues so the Government needs to consult widely and then clearly outline the ethical framework for industrial and academic researchers who will be creating or accessing large databases of patients.

The newly created NHS Connecting for Health agency is establishing electronic records to store a patient’s history. Incorporating genetic data into this system would be invaluable but the ability for researchers to return to patients to take samples if necessary will be essential. Clear guidelines are needed for what will and will not be possible.

Public attitudes
Alongside the evidence gathered from academic researchers, industry and other institutions, the working group which produced the report held a series of public dialogue meetings. They showed that there is concern about whether the current healthcare arrangements could successfully deliver genetic technology in the future. On balance, participants thought that the introduction of pharmacogenetics was likely to be beneficial. However, a significant minority were concerned about the increasing use of genetic tests in society.

One of the most pressing issues they identified, which was highlighted in the report, was that with large repositories of pharmacogenetic data being held, there is a need for adequate ethical and consent guidelines. This is to ensure patients are happy with how their data are being used while the maximum benefit to society is gained from analysing the data, including being able to return to patients to obtain genetic samples if necessary.

While participants considered the NHS most appropriate to control access to genetic testing, concerns were raised about whether appropriate safeguards could be given to ensure the accurate, reliable and confidential use of such tests.

International dimensions
Worldwide, greater harmonisation of research practice is needed. Variation in the laws for conducting genetic research between countries makes it difficult to combine data from across the globe into large-scale clinical trials. The guidelines and regulations for conducting genetic research across international borders need reviewing by the Department of Health in conjunction with the International Conference on Harmonisation.

Pharmacogenetics may prove valuable in the fight against the big killers worldwide, such as malaria, tuberculosis and HIV. Research is needed to establish the cost-effectiveness and clinical value of this approach for developing countries.

The report endorses the World Health Organisation’s recommendation that the introduction of simple DNA tests for genetic and infectious diseases in developing countries is vital. This would be valuable in the treatment of malaria, for example, where a single gene difference in a red blood cell enzyme causes severe anaemia when a particular type of anti-malarial drug is taken. Hundreds of thousands of people in tropical countries carry the gene and a simple stick test needs to be developed to prevent them exposing themselves to this risk.

Sir David Weatherall FRS is Chair of the Royal Society working group on personalised medicines