Personalised medicine is a slightly slippery term, since medicine can be bespoke with respect to a patient’s biological features (affecting probabilities of outcomes) or a patient’s psychology (affecting preferences / values / utilities). Ideally, medicine should, as much as possible, be tailored to both. But in this short blog we will concentrate on medicine that is personalised on the basis of biology (precision medicine, if you like). We select this focus because it is becoming increasingly possible to focus treatment according to different, often genetic, test results. Previously treatment was determined by the clinical diagnosis formed on the basis of clinical and standard tests, such as the ECG, image or biochemistry. However, a much finer level of granularity is increasingly available as a result of genetic testing. This type of precision medicine is increasingly important for cancer where interest has focussed on somatic (acquired), as well as germ-line (inherited), genetic variation. Treatment is no longer based purely on tissue of origin and histological appearance, but on the genetic mutations that are part and parcel of the carcinogenic process and that strongly influence responses to treatment. Treatment is also influenced by genetic factors affecting non-cancer diseases, but in this case it will be inherited, rather than acquired, genetic variations that are salient. Lastly, inherited genetic variations may provide advance warning that certain patients can, or cannot, tolerate certain treatments – pharmacogenetics.
Since CLAHRCs are concerned with how the service must adapt to improve access to safe and effective care, precision medicine is a topic of relevance to CLAHRCs, and a point of contact between service delivery and biomedical researchers.
But what are the service change requirements of precision medicine? Well, many new targetted therapies have no real service implications since they simply involve substitution of one medicine for another. The service implications are nugatory in a health service that already has well developed and smoothly functioning supply chains that can ensure availability of the relevant drugs. However, precision medicine is not always so straightforward, so here are some scenario types where the service may need to be adapted to a degree.
First, genetic diagnosis has an important collateral effect that arises when the laboratory findings have implication for the individual that lie outside the presenting feature. For instance, a genetic test in a patient with breast cancer may show that she has a high risk of cancer of the ovary. Preparing for such a scenario has human resource and educational implications. These might be somewhat modest, but more radical implications arise when a finding in one person may impact other family members who are often scattered across the world. This raises logistical issues in arranging for people to be contacted, counselled and tested. The workload and hence human resource implications are considerable. Currently, a project called the “100,000 genomes project,” is unfolding in England. Genetic samples are being taken from patients with numerous diseases. This is the basis for a tractable research project to model the service implications of enhanced genetic testing. CLAHRC WM collaborators at the Health Services Management Centre, University of Birmingham are investigating this issue with support from the regional West Midlands Academic Health Science Network (WM AHSN). Clearly, the ‘new genetics’ is going to have quite large service implications and we should prepare for it in advance.
Second, patients may obtain testing privately and then present to publically funded services with the results. The service needs to ensure that it has the capacity to respond, at the very least, by ensuring that accurate counselling is available. Continued professional development will be needed to ensure that staff are up to date. The resource implications may be mitigated by making information available online or even establishing online question and answer facilities. Informal testing also has implications for regulatory oversight of providers of genetic testing to ensure high-quality and prevent testing for attributes that society deems it inappropriate to test for.
Third, there are implications for health economic evaluation and the cost-effectiveness of targeted therapies. However, the principle behind precision medicine is that the effect of therapy will be greater when therapy is targeted. That means that companies should be able to charge more for their medicines per patient to recoup costs. However, the general improvement in effectiveness will have disequilibrium effects, meaning that, ceterus parabus, the willingness-to-pay threshold for a QALY will have to deflate. Precision medicine does, of course, have implications for the private insurance industry since they will be on guard to ensure that they are not exposed to moral hazard when people have covert testing and only declare this if their risk is low.
Taken in the round, however, precision medicine would seem to have real, but fairly, modest service delivery implications. But we do need to plan carefully by evaluating the human resource and educational implications of dealing with collateral effects and making sure that necessary testing capacity is scaled to predicted demand.
There is another kind of precision medicine with more radical service implications, and this is the genotypic approach to characterising microbes. This has large implications for two reasons. First, existing microbial typing laboratory procedures will become obsolete (or demand for them will be greatly reduced), with implications for retraining and possible redundancy. Second, testing may well move from the lab back into the ward with large implications for education of the clinical workforce.
Although precision medicine may have rather modest implications for service delivery, there are other lab discoveries with much greater implications. For example, cell therapy has large implications for service delivery, quality control, and methods for up-scaling, and new treatments come along, some of which change pathways completely, such as intracranial thrombectomy for stroke, as discussed in a previous blog.
— Richard Lilford, CLAHRC WM Director
- Lilford R. Provocative Idea for Thrombectomy Services in Acute Stroke. NIHR CLAHRC West Midlands News Blog. 14 August 2015.