Stratified Medicine Scotland Innovation Centre (SMS-IC)
A win–win solution for medicine …
Profile Stratified Medicine Scotland Innovation Centre (SMS-IC)
ADMIN HUB: University of Glasgow
FUNDING: £8 million (initial investment)
A win–win solution for medicine
Pharmaceuticals and healthcare are about to change forever – thanks to a better understanding of the genetic background and molecular mechanisms of disease and individual responses to medical treatments, using a new approach to medical science and patient treatment called stratified medicine. And Scotland is emerging as the ideal place to develop and showcase this 21st-Century medical science.
Stratified medicine requires collaboration across many branches of science, as well as the cooperation of a large group of patients. By analysing blood and tissue samples from a large number of people, whose data is anonymised, researchers can divide them into 'stratified' groups based on the link between their DNA profile and their responses to the drugs they are prescribed, so that future treatment of patients with similar profiles can be customised to particular drugs – instead of trying different treatments one after another until you find one that will work.
This new approach will not just improve the way many chronic diseases are treated, but also change the way that drugs are developed, and the structure of the global pharmaceutical industry. Patients will get treatments more precisely calibrated to their needs, and governments and healthcare providers will be able to rationalise annual budgets. Pharmaceutical companies will find a new route to survive in an increasingly competitive environment by being able to better predict the outcome of their clinical trials, thus making the R&D model more sustainable. New healthcare companies will also emerge, specialising in various aspects of medical science, where information technology will frequently play a key role.
The development of stratified medicine is being driven by advances in science and technology, including the emergence of high-speed genetic sequencing and a new science called bioinformatics, which analyses patient records; much the same as finding trends in other 'big data’ sets. And Scotland is well placed to be a major player in this 'game-changing' science by setting up a new Innovation Centre for stratified medicine – an initiative with implications far beyond the borders of Scotland.
Problems and solutions
Stratified medicine has been described as “a win–win solution for healthcare” because it offers benefits to everyone – from individual patients to large corporations.
Everyone wants better, more predictable treatments and everyone wants lower costs. But the success rate for new drugs is falling, and pharmaceutical companies are beginning to struggle – only one in every 70 new pharmaceutical development projects reaches the market. For many drug developers, “the goalposts have moved” and they’ve been forced to change their attitude to risk as a result.
Pharmaceutical companies develop new products over a 10–15-year timescale, at an average cost believed to be in excess of £1.2 billion. A successful drug approval may generate significant profits for a limited number of years (money which is needed to support new research projects). When the drug’s patent runs out, the profits shrink rapidly due to generic drug competition. How do they replace that source of revenue when it takes so long and costs so much to develop new drugs? The metrics are not good.
After several years in ‘discovery,’ the drugs enter clinical trials – to be tested on humans – and many of these frequently fail at this stage because they don’t perform significantly better than placebos. It is estimated that out of the £595 billion spent by the global industry on pharmaceuticals in 2011, £393 billion went to develop therapies “which did not produce the desired effect.” This not only means a loss of investment and profits, but also adds to future costs, and if the process is repeated again and again, the corporation could go out of business – and who would develop new drugs? Current projections on the rate of new drug approvals indicate that the predicted revenue streams will not keep up with the loss of revenue from drugs whose patents will expire in the near future.
To 'fail' its trial does not necessarily mean that the new pharmaceutical is not effective – it may simply not be effective enough on average for the trial population that typically is chosen to represent the entire spectrum of the disease – referred to as ‘all comers.’ But what if new drugs could be targeted at groups of ‘stratified’ patients, not just the whole ‘all comers’ population, and thus increase the chances of success for drug discovery? Instead of always aiming to develop ‘gold-medal’ drugs, the pharmaceutical companies could develop more ‘bronze-medal’ drugs. Because these would be targeted at only a sub-set of patients, they would generate less profit per drug, with a higher probability of success in the clinical trials. By making the drug trials more predictively effective, albeit for a smaller segment of the patient population, the idea is that this could significantly impact the future of the pharmaceutical industry in a positive way. This is the solution that stratified medicine could soon deliver, via a collaboration between government, healthcare providers, information technology companies, genetics specialists and pharmaceutical companies in projects such as the SMS-IC – the Stratified Medicine Scotland Innovation Centre in Glasgow.
Currently based in the Thermo Fisher Scientific site at Paisley, the SMS-IC will move into the new South Glasgow Hospitals Campus during 2015. Researchers will have access to sequenced human genomes and clinical data, and a new Clinical Research Facility for stratified clinical trials. With initial funding adding up to £20 million, including £8 million from the Scottish Research Fund, the Centre involves a consortium of universities (Aberdeen, Dundee, Edinburgh and Glasgow), NHS Scotland (NHS Grampian, NHS Greater Glasgow, NHS Lothian and NHS Tayside) and two key business partners – Thermo Fisher Scientific and Aridhia Informatics. Other supporting industry partners include GSK, Astra Zeneca, Novartis and Quintiles, as well as Scottish companies Arrayjet, Axis Shield, Biopta, DestiNA Genomics, Fios Genomics and Sistemic Ltd.
The SMS-IC Core laboratory is equipped with a state-of-the-art SMART laboratory comprising a suite of Ion-Torrent® nextgenDNA sequencing platforms and a purpose-built high-capacity compute platform provided through its industrial partners, Thermo Fisher Scientific and Aridhia Informatics. This capability allows the team to generate whole genome sequence data from anonymised patient samples to assemble the sequence data and compare this with clinical data relating to response (or the lack of response) to drug therapy. The facility has the capacity to sequence over 1,000 individuals per year, and this could be further enhanced by moving to multiple-shift operation.
The SMS-IC will initially focus on developing new treatment regimes for chronic diseases, including cancer, diabetes, rheumatoid arthritis and respiratory and cardiovascular diseases. Professor Anna Dominiczak (left), Vice-Principal and Regius Professor of Medicine at the University of Glasgow, believes that stratified medicine will change the way we practise medicine, and said when the Centre was announced: “The SMS-IC is a once-in-a-lifetime opportunity to combine our strengths in life science, NHS health delivery and academic medicine to produce world-leading innovations for treatment of chronic diseases. The UK spends £124 billion on health care each year, including £12 billion on medicines, so even a small increase in efficiency through better targeting of treatment would save the UK a significant amount.”
According to Professor David Newby (right) of the University of Edinburgh, who is Director of Research and Development for NHS Lothian and a member of the SMS-IC Executive Board, the benefits of the new Centre will be felt throughout Scotland, and the regional health boards will each contribute specialist studies. For example, NHS Lothian has specialists doing research on cardiology and ovarian cancer, tracking outcomes based on patient profiles. It is also using innovative imaging methods “to identify unstable coronary plaques,” as part of a stratified medicine study.
“The aim of these studies and the work of the SMS-IC is to optimise the use of patient records, to deliver the right treatment for the right patient, and better overall health care,” says Newby. “Scotland is both big enough and small enough to be a leader in stratified medicine – big enough in terms of the available data and small enough to make it easier to bring different organisations together.”
The new Centre will pioneer procedures, processes and ultimately engagement with the NHS, for what could become full genetic-based clinical trials. It will also act as the accelerator for genomics, biomarker and companion diagnostics and bioinformatic research in Scotland, including its SME base, “catalysing interactions between clinical academia, informatics and computer science across Scotland and with world leaders in big data provision and analytics.”
Another major aim is to invest in developing academic entrepreneurs in Biomedical Informatics, providing new specialist post-graduate courses in Applied Genomics and Informatics.
An independent economic impact assessment has forecast that the Centre could generate more than 300 jobs and contribute up to £68 million to the Scottish economy over its initial five-year funding period. The Centre also aims to attract enough funding from industry partners to become self-sustaining within five years.
David Sibbald, Chairman and CEO of Aridhia, said: “The SMS-IC is a globally significant programme to determine the future of health care in the 21st Century. With the cost of sequencing an individual’s genome continuing to fall rapidly, we need to understand how to find and unlock the associations with clinical and patient data in order to improve diagnosis and to personalise the treatment of disease to the individual patient. By combining our expertise with our academic, clinical and commercial partners, we can change the way healthcare is delivered forever, and create economic growth for Scotland.”
As well as joining forces to develop new solutions for health care, the partners in the SMS-IC recognise the need to win the hearts and minds of the general public, convincing people it is in their interest to be ‘stratified’ according to their genes, and allow their patient records to be used in research, with appropriate measures in place to ensure confidentiality by ‘anonymising’ all individuals involved. The SMS-IC and leading clinicians involved will also need to work closely with government agencies and regulators to enable stratified medicine to become a standard component of healthcare provision, promoting the benefits in terms of better health outcomes and economics. Another major task will be to educate the next generation of medical doctors so they are equipped with the knowledge to take full advantage of stratified medicine in the future – for example, learning more about genetic population distributions.
The SMS-IC will not only partner with leading organisations such as Thermo Fisher Scientific and Aridhia, but also help smaller companies interact with healthcare providers such as the NHS. The new Centre will also seek to partner with healthcare providers, academic researchers and pharmaceutical companies in countries all over the world. Other exciting initiatives are emerging in Estonia, Saudi Arabia, England and the USA, and it is hoped that these projects can ultimately collaborate to advance the science and raise Scotland’s profile in the medical world.
What is stratified medicine?
Stratified, or ‘personalised’, medicine identifies subgroups of patients who respond in different ways to different therapies, based on their distinct genetic profile. This allows the pharmaceutical industry and healthcare providers to develop treatments tailored to the needs of individual groups of patients – to make the right decision and ensure that the right patient gets the right treatment at the right time.
According to Professor Iain McInnes of the University of Glasgow, “only a proportion of patients will respond well to any given treatment,” but in those people such treatment could make a critical difference – the challenge is to know in advance who those people will be for any given medicine, then develop drugs which target the correct patient group right from the start. “That will bring us the optimal chance of achieving long-term remission, which is what patients tell us they value most as a target,” he adds.
This new approach to healthcare and pharmaceutical development will have an impact not just on patients but also health service providers, government and the pharmaceutical industry.
For patients, it promises significant improvements in treatment, including safer drugs, shorter waiting times for treatments to begin, and faster recovery. Drug therapies will be less ‘hit or miss’ and offer a much higher rate of success. Fewer patients will receive a treatment only to discover some time later that it will not be effective – for example, sufferers from rheumatoid arthritis who may wait up to two years to find the right treatment, and may suffer liver damage as a result. As one researcher put it: “Patients don’t want to wait two years for nothing to happen – they simply want the medicine to work as soon as possible.”
Health service providers such as the UK’s National Health Service (NHS) also stand to reap enormous benefits, not just by offering their patients better standards of health care but also by reducing waste and lowering the total cost of treatments, as well as the overall budget for drugs – an estimated ten per cent of which is spent on diabetes alone. In addition, stratified medicine will make it easier to identify people who are likely to experience adverse reactions to drugs, and thus increase safety at the same time as lowering risks.
For government and society at large, the economic benefits will extend beyond savings in healthcare by getting people back to work quicker because they are receiving better treatment and recovering sooner, thus reducing the burden on the social security budget and other expenditure.
The pharmaceutical industry will benefit in a number of ways. Instead of having to develop drugs for the whole population, they will be able to target specific genetic groups. Drugs which may have failed clinical trials because they only treated a small percentage of people may reach the market sooner because they are effective for that group of people. In other words, no single drug will cure every form of cancer in every person, but many different drugs may be effective for specific groups of people. Drug development will also be more effective because the ‘target’ will be better defined from the start, and fewer drugs will be rejected because they are not ‘cure-alls.’
Scotland offers several advantages as a stratified medicine development centre, including the unfortunate fact that the country has high rates of cancer, diabetes and cardiovascular illness – the major killers in developed countries.
The patient base is not just large, but easier to study, because the population also tends not to move far from home – annual mobility is roughly one to two per cent, compared to about nine per cent in major cities such as London.
Integrated electronic patient records also make it easier to analyse trends, with most people served by a single health service provider – the National Health Service (NHS) – rather than multiple agencies. This means that researchers can drill down into details at the same time as seeing the ‘big picture,’ using ‘big data’ to measure the effectiveness of individual treatments, as well as identify national patterns.
In a recent interview in Holyrood Magazine, the Chairman of the SMS-IC, David U'Prichard, said: “Scotland probably has the highest-quality patient information base in the world.” He also thinks the partnership between Thermo Fisher Scientific and Aridhia, combined with access to NHS data, will allow Scotland “to pioneer a concrete, results- and business-oriented application of the grand theory of ‘stratified medicine’ more speedily than elsewhere in the world.”
U'Prichard is also confident that the SMS-IC will have real ‘proof-of-concept’ data within three years, and “blaze the trail for similar, even larger, projects in Europe, the US and Asia, and rapidly build a position as a – maybe the – global centre of excellence for population-based phenotypic/genotypic analysis.”
The Scottish NHS’s e-Health systems can provide high-quality, patient information across different disease populations, “probably better than anywhere else in the world,” he added. Combined with genomic data, “this will allow new drug development to be much more sharply and effectively focused, promising greater and potentially faster therapeutic benefit to patients, and I believe our development of SMS-IC will result in clinical trials of new drugs in Scotland using stratified medicine approaches.”