The future of stratified medicine

Posted on July 23, 2013 by

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Abigail Perrin from the Academy of Medical Sciences talks us through their new report, “Realising the potential of stratified medicine”, which outlines the challenges facing the adoption of stratified medicine in the UK and recommends a course of action whereby it could be best implemented.

Background

The 21st century has already seen great strides in genomics and molecular biology which have vastly accelerated our understanding of the biological basis of disease.  Within what we would classically consider a single disease, we are becoming increasingly able to identify sub-categories with distinct underlying molecular characteristics; this has knock-on implications for patient care, such that therapeutic interventions can be ‘stratified’ based on the sub-categorisation of their particular case.  For most treatments currently in use in the NHS, only between 30 – 70% of patients are expected to show an improvement.  Stratified medicine aims to dramatically boost these odds.

Breast cancer treatment was one of the very first to be stratified, and can provide a useful example of how stratified medicine can be a better approach to therapy. In about a quarter of early-stage breast tumours the HER2 gene is overexpressed, resulting in a massive over-representation of epidermal growth factor receptor (EGF-R) on the surface of the cell. This sensitises the affected cell to growth signals, causing rapid division and tumour growth.  In these cases, trastuzumab – an antibody that targets the over-represented receptors that mark the cancer cells – is a good treatment option.  However, in the remainder of cases, trastuzumab is certainly not a good treatment option, offering little hope of curing disease whilst still exposing the patient to side effects. Using a test that distinguishes HER2 overexpressing tumours, doctors are well placed to give an effective treatment to patients who are likely to benefit, whilst avoiding treating others with a drug that will be ineffective.

Stratified medicine has proven benefit in the treatment of a number of other cancers and genetic diseases. It is also used to streamline patients who may have an adverse reaction to an antiviral drug.  Researchers are identifying more and more biomarkers (biological characteristics that can be used to sub-categorise diseases) that could be used to refine treatments in the future. The Academy of Medical Sciences held a workshop in 2007 that identified the benefits to patients, healthcare systems and industry of stratified approaches to therapy. This new report aims to address the residual barriers to widespread development and implementation, and outlines how the potential benefits of these discoveries can be realised.

What are the major barriers?

From development through to implementation, there are a number of issues facing the widespread adoption of stratified medicine within the NHS.

Practical challenges

Despite early successes, there are practical challenges in the future identification and validation of biomarkers. Large, accessible datasets containing patient information with appropriate safeguards are an invaluable resource for researchers in this field, but the UK currently lacks the infrastructure for the collection, standardisation and secure storage of the necessary quantity and quality of relevant data.

Financial disincentives

Currently, stratified medicines require the development of a ‘companion’ diagnostic by which candidates for drug treatment can be selected. Herein lies a financial ‘double disincentive’ for pharmaceutical companies to stratify medicines; they stand to pay more for R&D and see their market size shrink.

Regulation

Once in development, prospective medicines and accompanying diagnostics must each be regulated but the current system is not well suited for stratified medicine products. There needs to be greater co-ordination between the regulators of drugs and devices. Furthermore, the smaller target populations mean that drug regulation will need to adapt to allow for smaller trial sizes, and different forms of data collection. In addition, diagnostics are currently under much less stringent regulatory control than drugs. As the results of these tests determine which patients receive which treatment, it is important that they are more tightly standardised and assessed for accuracy and reliability.

Adoption of new medicines to treat patients

After development there can be obstacles in the implementation of stratified medicine in health services. The additional ‘stratification’ step between diagnosis and treatment will require that healthcare practitioners receive additional training to ensure that these changes are implemented in healthcare systems.

The way forward

The report makes 18 recommendations to pave the way for an increasingly stratified approach to medicine in the UK, and suggests that patient and public involvement should be embedded in steering its development and implementation.

A more robust informatics infrastructure

Efforts are already underway to allow researchers regulated access to anonymous patient information, which could prove extremely valuable for the discovery of useful diagnostic biomarkers for stratified medicine. The report encourages the establishment of data-sharing resources and suggests that stronger links are established between health services, academic institutions and industrial partners to make the best use of the data. A key element in the success of such resources will be their regulation and co-ordination, such that patient data is stored and shared securely.

Better regulation of ‘companion’ diagnostics

Last year the European Commission drafted a proposal for in vitro diagnostics regulation, calling for much more stringent requirements for companies to provide clinical evidence for the quality, accuracy and utility of these diagnostics. These plans were welcomed in the Academy’s report, and some of the recommendations are relevant to shaping the ongoing development of these proposals.

Developing financial incentives for innovation in the field

Although new legislation for the regulation of diagnostics is very necessary, it places an even greater burden on developers. To address the financial barriers to investment, the report suggests ways in which drug stratification and diagnostic development could be incentivised. Progress in this area would be best rewarded by a flexible pricing structure which is tied to the value of the product; this could be evaluated based on factors including the costs of prescribing drugs to, and treating side effects in, those who don’t benefit from a drug.

Building collaboration.

At present the UK Stratified Medicines Innovation Platform brings together research funders, health professionals and regulators to champion the development of stratified medicines in the UK.  By their expansion to work together with industrial partners, informatics experts, investors and patient groups, a very positive contribution could be made towards realising the potential of stratified medicine.

Posted in: Policy